Scholars@Duke
Anna Mae Diehl

Anna Mae Diehl

Florence McAlister Distinguished Professor of Medicine
Medicine, Gastroenterology
diehl004@mc.duke.edu
Duke Box 3256, 905 S. LaSalle Street, GSRB 1, Durham, NC 27710
Ste 1073, GSRB 1, 595 LaSalle Street, Durham, NC 27710

Selected Publications

PNPLA3 rs738409, age, diabetes, sex, and advanced fibrosis jointly contribute to the risk of major adverse liver outcomes in metabolic dysfunction-associated steatotic liver disease.

Journal Article Hepatology · November 1, 2024 BACKGROUND AND AIMS: The patatin-like phospholipase domain-containing protein 3 ( PNPLA3 ) rs738409 variant is associated with steatotic liver disease and its progression. We examined the association between PNPLA3 and the development of major adverse live ... Full text Link to item Cite

A systemic effect for liver senescence.

Journal Article Nature cell biology · November 2024 Full text Cite

Osteopontin Promotes Cholangiocyte Secretion of Chemokines to Support Macrophage Recruitment and Fibrosis in MASH.

Journal Article Liver Int · October 18, 2024 BACKGROUND AND AIMS: Osteopontin (OPN) promotes the ductular reaction and is a major driver of chronic liver disease (CLD) progression. Although CLD is characterised by the accumulation of inflammatory cells including macrophages around the peri-portal reg ... Full text Link to item Cite

Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD.

Journal Article J Hepatol · October 2024 BACKGROUND & AIMS: The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with non-alcoholic fatty liver disease (NAFLD) is not well-understood. We prospectively defined ra ... Full text Link to item Cite

Envisioning how to advance the MASH field.

Journal Article Nat Rev Gastroenterol Hepatol · October 2024 Since 1980, the cumulative effort of scientists and health-care stakeholders has advanced the prerequisites to address metabolic dysfunction-associated steatotic liver disease (MASLD), a prevalent chronic non-communicable liver disease. This effort has led ... Full text Link to item Cite

The senescence-associated secretome of Hedgehog-deficient hepatocytes drives MASLD progression.

Journal Article J Clin Invest · August 27, 2024 The burden of senescent hepatocytes correlates with the severity of metabolic dysfunction-associated steatotic liver disease (MASLD), but the mechanisms driving senescence and how it exacerbates MASLD are poorly understood. Hepatocytes experience lipotoxic ... Full text Link to item Cite

Liver stiffness progression in biopsy-proven metabolic dysfunction-associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study.

Journal Article Hepatology · July 19, 2024 BACKGROUND AND AIMS: There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dy ... Full text Link to item Cite

The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

Journal Article Am J Gastroenterol · July 17, 2024 INTRODUCTION: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrho ... Full text Link to item Cite

Effects of Food Insecurity on Hepatic Steatosis and Fibrosis in People With HIV.

Journal Article Clin Gastroenterol Hepatol · July 2024 BACKGROUND & AIMS: Food insecurity (FI) is a risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis in the general population, but its impact on liver disease in people with HIV (PWH) is unknown. METHODS: We examined the association ... Full text Link to item Cite

Aging promotes metabolic dysfunction-associated steatotic liver disease by inducing ferroptotic stress.

Journal Article Nat Aging · July 2024 Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data ... Full text Link to item Cite

Plasticity, heterogeneity, and multifunctionality of hepatic stellate cells in liver pathophysiology.

Journal Article Hepatol Commun · May 1, 2024 HSCs, the resident pericytes of the liver, have consistently been at the forefront of liver research due to their crucial roles in various hepatic pathological processes. Prior literature often depicted HSCs in a binary framework, categorizing them as eith ... Full text Link to item Cite

A humanized mouse model for adeno-associated viral gene therapy.

Journal Article Nat Commun · March 4, 2024 Clinical translation of AAV-mediated gene therapy requires preclinical development across different experimental models, often confounded by variable transduction efficiency. Here, we describe a human liver chimeric transgene-free Il2rg-/-/Rag2-/-/Fah-/-/A ... Full text Link to item Cite

Alterations in zonal distribution and plasma membrane localization of hepatocyte bile acid transporters in patients with NAFLD.

Journal Article Hepatol Commun · March 1, 2024 BACKGROUND: NAFLD is highly prevalent with limited treatment options. Bile acids (BAs) increase in the systemic circulation and liver during NAFLD progression. Changes in plasma membrane localization and zonal distribution of BA transporters can influence ... Full text Link to item Cite

Thyroid hormone receptor alpha modulates fibrogenesis in hepatic stellate cells.

Journal Article Liver Int · January 2024 OBJECTIVE: Progressive hepatic fibrosis can be considered the final stage of chronic liver disease. Hepatic stellate cells (HSC) play a central role in liver fibrogenesis. Thyroid hormones (TH, e.g. thyroxine; T4 and triiodothyronine; T3) significantly aff ... Full text Link to item Cite

Lower hepatic CBS and PEMT expression in advanced NAFLD: inferencing strategies to lower homocysteine with a mathematical model

Journal Article Metabolism and Target Organ Damage · January 1, 2024 Aim: Hepatic homocysteine (Hcy) accumulation promotes inflammation and fibrosis in experimental nonalcoholic fatty liver disease (NAFLD), while vitamin B12 and folate reduce hepatic Hcy and protect animals from nonalcoholic steatohepatitis. This suggests c ... Full text Cite

Nutrition assessment and MASH severity in children using the Healthy Eating Index.

Journal Article Hepatol Commun · December 1, 2023 BACKGROUND: Pediatric metabolic-associated fatty liver disease (MAFLD) is a global health problem, with lifestyle modification as its major therapeutic strategy. Rigorous characterization of dietary content on MAFLD in children is lacking. We hypothesized ... Full text Link to item Cite

Hepatic NLRP3-Derived Hsp70 Binding to TLR4 Mediates MASLD to MASH Progression upon Inhibition of PP2A by Harmful Algal Bloom Toxin Microcystin, a Second Hit.

Journal Article Int J Mol Sci · November 15, 2023 Harmful algal bloom toxin microcystin has been associated with metabolic dysfunction-associated steatotic liver disease (MASLD) progression and hepatocellular carcinoma, though the mechanisms remain unclear. Using an established mouse model of MASLD, we sh ... Full text Link to item Cite

Hedgehog Signaling: Implications in Liver Pathophysiology.

Journal Article Semin Liver Dis · November 2023 The purpose of this review is to summarize current knowledge about the role of the Hedgehog signaling pathway in liver homeostasis and disease. Hedgehog is a morphogenic signaling pathway that is active in development. In most healthy tissues, pathway acti ... Full text Link to item Cite

Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

Journal Article Hepatology · October 1, 2023 BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes a ... Full text Link to item Cite

Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study.

Journal Article Gastroenterology · August 2023 Background & aimsThere are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis pro ... Full text Cite

Serum Metabolites Are Associated With HFpEF in Biopsy-Proven Nonalcoholic Fatty Liver Disease.

Journal Article J Am Heart Assoc · July 18, 2023 Background Nonalcoholic fatty liver disease (NAFLD) and heart failure with preserved ejection fraction (HFpEF) share common risk factors, including obesity and diabetes. They are also thought to be mechanistically linked. The aim of this study was to defin ... Full text Link to item Cite

Antagonizing the irreversible thrombomodulin-initiated proteolytic signaling alleviates age-related liver fibrosis via senescent cell killing.

Journal Article Cell Res · July 2023 Cellular senescence is a stress-induced, stable cell cycle arrest phenotype which generates a pro-inflammatory microenvironment, leading to chronic inflammation and age-associated diseases. Determining the fundamental molecular pathways driving senescence ... Full text Open Access Link to item Cite

Targeting YAP-mediated HSC death susceptibility and senescence for treatment of liver fibrosis.

Conference Hepatology · June 1, 2023 BACKGROUND AND AIMS: Liver fibrosis results from the accumulation of myofibroblasts (MFs) derived from quiescent HSCs, and yes-associated protein (YAP) controls this state transition. Although fibrosis is also influenced by HSC death and senescence, whethe ... Full text Link to item Cite

Rescue of glutaric aciduria type I in mice by liver-directed therapies.

Journal Article Sci Transl Med · April 19, 2023 Glutaric aciduria type I (GA-1) is an inborn error of metabolism with a severe neurological phenotype caused by the deficiency of glutaryl-coenzyme A dehydrogenase (GCDH), the last enzyme of lysine catabolism. Current literature suggests that toxic catabol ... Full text Link to item Cite

Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease.

Journal Article Journal of hepatology · April 2023 Background & aimsDespite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological ... Full text Cite

The imprinted gene Zac1 regulates steatosis in developmental cadmium-induced nonalcoholic fatty liver disease.

Journal Article Toxicol Sci · January 31, 2023 Cadmium (Cd) exposure in adulthood is associated with nonalcoholic fatty liver disease (NAFLD), characterized by steatosis, inflammation, and fibrosis. The prevalence of NAFLD in children is increasing, suggesting a role for the developmental environment i ... Full text Link to item Cite

Hepatocyte Smoothened Activity Controls Susceptibility to Insulin Resistance and Nonalcoholic Fatty Liver Disease.

Conference Cell Mol Gastroenterol Hepatol · 2023 BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH), a leading cause of cirrhosis, strongly associates with the metabolic syndrome, an insulin-resistant proinflammatory state that disrupts energy balance and promotes progressive liver degeneration. We a ... Full text Link to item Cite

Challenges and barriers in hepatocellular carcinoma (HCC) surveillance for patients with non-alcoholic fatty liver disease (NAFLD)

Journal Article Hepatoma Research · January 1, 2023 The proportion of hepatocellular carcinoma (HCC) cases due to NAFLD is expected to increase, paralleling the rise in NAFLD due to the obesity epidemic. Early detection is critical, as it potentially enables curative treatment. Current guidelines recommend ... Full text Cite

Deep learning-based quantification of NAFLD/NASH progression in human liver biopsies.

Journal Article Sci Rep · November 10, 2022 Non-alcoholic fatty liver disease (NAFLD) affects about 24% of the world's population. Progression of early stages of NAFLD can lead to the more advanced form non-alcoholic steatohepatitis (NASH), and ultimately to cirrhosis or liver cancer. The current go ... Full text Link to item Cite

Alterations in DNA methylation associate with fatty liver and metabolic abnormalities in a multi-ethnic cohort of pre-teenage children.

Journal Article Epigenetics · November 2022 Non-Alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. Epigenetic alterations, such as through DNA methylation (DNAm), may link adverse childhood exposures and fatty liver and provide non-invasive methods for i ... Full text Link to item Cite

Zac1 and the Imprinted Gene Network program juvenile NAFLD in response to maternal metabolic syndrome.

Journal Article Hepatology · October 2022 BACKGROUND AND AIMS: Within the next decade, NAFLD is predicted to become the most prevalent cause of childhood liver failure in developed countries. Predisposition to juvenile NAFLD can be programmed during early life in response to maternal metabolic syn ... Full text Link to item Cite

Dynamics of hepatocyte-cholangiocyte cell-fate decisions during liver development and regeneration.

Journal Article iScience · September 16, 2022 The immense regenerative potential of the liver is attributed to the ability of its two key cell types - hepatocytes and cholangiocytes - to trans-differentiate to one another either directly or through intermediate progenitor states. However, the dynamic ... Full text Link to item Cite

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression.

Journal Article Nat Commun · September 3, 2022 Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination ... Full text Link to item Cite

Aging reduces liver resiliency by dysregulating Hedgehog signaling.

Conference Aging Cell · February 2022 Older age is a major risk factor for damage to many tissues, including liver. Aging undermines resiliency and impairs liver regeneration. The mechanisms whereby aging reduces resiliency are poorly understood. Hedgehog is a signaling pathway with critical m ... Full text Link to item Cite

Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms.

Journal Article PLoS One · 2022 BACKGROUND AND AIMS: Management of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® param ... Full text Link to item Cite

Nonalcoholic Fatty Liver Disease and Risk of Heart Failure Among Medicare Beneficiaries.

Journal Article J Am Heart Assoc · November 16, 2021 Background Nonalcoholic fatty liver disease (NAFLD) and heart failure (HF) are increasing in prevalence. The independent association between NAFLD and downstream risk of HF and HF subtypes (HF with preserved ejection fraction and HF with reduced ejection f ... Full text Link to item Cite

Relationship of Nonalcoholic Fatty Liver Disease and Heart Failure With Preserved Ejection Fraction.

Journal Article JACC Basic Transl Sci · November 2021 Although there is an established bidirectional relationship between heart failure with reduced ejection fraction and liver disease, the association between heart failure with preserved ejection fraction (HFpEF) and liver diseases, such as nonalcoholic fatt ... Full text Link to item Cite

Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease.

Journal Article The New England journal of medicine · October 2021 BackgroundThe prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.MethodsWe prospectively followed a multicenter patient p ... Full text Cite

Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice.

Journal Article iScience · September 24, 2021 Cellular cholesterol is regulated by at least two transcriptional mechanisms involving sterol-regulatory-element-binding proteins (SREBPs) and liver X receptors (LXRs). Although SREBP and LXR pathways are the predominant mechanisms that sense cholesterol i ... Full text Link to item Cite

Glycemic Control Predicts Severity of Hepatocyte Ballooning and Hepatic Fibrosis in Nonalcoholic Fatty Liver Disease.

Journal Article Hepatology · September 2021 BACKGROUND AND AIMS: Whether glycemic control, as opposed to diabetes status, is associated with the severity of NAFLD is open for study. We aimed to evaluate whether degree of glycemic control in the years preceding liver biopsy predicts the histological ... Full text Open Access Link to item Cite

Dysregulation of the ESRP2-NF2-YAP/TAZ axis promotes hepatobiliary carcinogenesis in non-alcoholic fatty liver disease.

Journal Article Journal of hepatology · September 2021 Background & aimsNon-alcoholic fatty liver disease (NAFLD), the hepatic correlate of the metabolic syndrome, is a major risk factor for hepatobiliary cancer (HBC). Although chronic inflammation is thought to be the root cause of all these diseases ... Full text Cite

Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells but exacerbates chronic liver injury.

Journal Article Liver Int · September 2021 BACKGROUND & AIMS: The outcome of liver injury is dictated by factors that control the accumulation of myofibroblastic (activated) hepatic stellate cells (MF-HSCs) but therapies that specifically block this process have not been discovered. We evaluated th ... Full text Link to item Cite

Tissues & organs

Chapter · July 29, 2021 Full text Cite

Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.

Journal Article Gastroenterology · July 2021 BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: ... Full text Link to item Cite

Glycogenosis is common in nonalcoholic fatty liver disease and is independently associated with ballooning, but lower steatosis and lower fibrosis.

Journal Article Liver Int · May 2021 BACKGROUND/AIMS: Glycogen synthesis and storage are normal hepatocyte functions. However, glycogenosis, defined as excess hepatocyte glycogen visible by routine H&E light microscopy, has not been well characterized in nonalcoholic fatty liver disease (NAFL ... Full text Link to item Cite

REPLY.

Journal Article Hepatology · April 2021 Full text Link to item Cite

Serum Bile Acid, Vitamin E, and Serotonin Metabolites Are Associated With Future Liver-Related Events in Nonalcoholic Fatty Liver Disease.

Journal Article Hepatol Commun · April 2021 Identifying patients at higher risk for poor outcomes from nonalcoholic fatty liver disease (NAFLD) remains challenging. Metabolomics, the comprehensive measurement of small molecules in biological samples, has the potential to reveal novel noninvasive bio ... Full text Link to item Cite

Sex and Menopause Modify the Effect of Single Nucleotide Polymorphism Genotypes on Fibrosis in NAFLD.

Journal Article Hepatol Commun · April 2021 The development of fibrosis in nonalcoholic fatty liver disease (NAFLD) is influenced by genetics, sex, and menopausal status, but whether genetic susceptibility to fibrosis is influenced by sex and reproductive status is unclear. Our aim was to identify m ... Full text Link to item Cite

Association of liver fibrosis risk scores with clinical outcomes in patients with heart failure with preserved ejection fraction: findings from TOPCAT.

Journal Article ESC Heart Fail · April 2021 AIMS: Non-alcoholic fatty liver disease leads to progressive liver fibrosis and appears to be a frequent co-morbid disease in heart failure with preserved ejection fraction (HFpEF). It is well known that liver fibrosis severity predicts future liver-relate ... Full text Link to item Cite

Cross-linkage between bacterial taxonomy and gene functions: a study of metagenome-assembled genomes of gut microbiota in adult non-alcoholic fatty liver disease.

Journal Article Aliment Pharmacol Ther · March 2021 BACKGROUND: The reconstruction of metagenome-assembled genomes (MAGs) has emerged as a powerful approach for combining the taxonomic and functional content of microbial populations. AIM: To use this new approach to highlight mechanisms linking gut microbio ... Full text Link to item Cite

Molecular Mechanisms Linking Nonalcoholic Steatohepatitis to Cancer.

Journal Article Clin Liver Dis (Hoboken) · January 2021 Watch a video presentation of this article Watch an interview with the author Answer questions and earn CME. ... Full text Link to item Cite

Inflammation Writes the Fibrogenic Code.

Journal Article Cell Mol Gastroenterol Hepatol · 2021 Full text Link to item Cite

Single-cell omics analysis reveals functional diversification of hepatocytes during liver regeneration.

Journal Article JCI Insight · November 19, 2020 Adult liver has enormous regenerative capacity; it can regenerate after losing two-thirds of its mass while sustaining essential metabolic functions. How the liver balances dual demands for increased proliferative activity with maintenance of organ functio ... Full text Link to item Cite

Multicenter Validation of Association Between Decline in MRI-PDFF and Histologic Response in NASH.

Journal Article Hepatology · October 2020 BACKGROUND AND AIMS: Emerging data from a single-center study suggests that a 30% relative reduction in liver fat content as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) from baseline may be associated with histologic impro ... Full text Link to item Cite

Succinate-GPR-91 receptor signalling is responsible for nonalcoholic steatohepatitis-associated fibrosis: Effects of DHA supplementation.

Journal Article Liver Int · April 2020 BACKGROUND AND AIMS: Treatment of non-alcoholic steatohepatitis (NASH) is challenging, because suppressing fibrotic progression has not been achieved consistently by drug candidates currently in clinical trials. The aim of this study was to investigate the ... Full text Link to item Cite

Epithelial splicing regulatory protein 2-mediated alternative splicing reprograms hepatocytes in severe alcoholic hepatitis.

Journal Article J Clin Invest · April 1, 2020 Severe alcoholic hepatitis (SAH) is a deadly liver disease without an effective medical therapy. Although SAH mortality is known to correlate with hepatic accumulation of immature liver cells, why this occurs and how it causes death are unclear. Here, we d ... Full text Link to item Cite

Developmental morphogens and adult liver repair

Chapter · January 24, 2020 Hedgehog and Notch are among the morphogenic signaling pathways that are typically inactivated once liver development finishes. Both pathways reactivate in adulthood in response to liver injury so that healthy liver tissue can be regenerated. Because these ... Full text Cite

Increased Glutaminolysis Marks Active Scarring in Nonalcoholic Steatohepatitis Progression.

Journal Article Cell Mol Gastroenterol Hepatol · 2020 BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSCs) and liver fibrogenesis in mice. However, it is unclear how changes i ... Full text Open Access Link to item Cite

Single-Cell RNA Sequencing Identifies Yes-Associated Protein 1-Dependent Hepatic Mesothelial Progenitors in Fibrolamellar Carcinoma.

Journal Article Am J Pathol · January 2020 Fibrolamellar carcinoma (FLC) is characterized by in-frame fusion of DnaJ heat shock protein family (Hsp40) member B1 (DNAJB1) with protein kinase cAMP-activated catalytic subunit α (PRKACA) and by dense desmoplasia. Surgery is the only effective treatment ... Full text Link to item Cite

Pre-transplant hepatic steatosis (fatty liver) is associated with chronic graft-vs-host disease but not mortality.

Journal Article PLoS One · 2020 Allogeneic-HCT (allo-HCT), while potentially curative, can result in significant complications including graft versus host disease (GVHD). Prior studies suggest that metabolic syndrome may be one risk factor for GVHD. We hypothesized that hepatic steatosis ... Full text Link to item Cite

Expression of mitochondrial membrane-linked SAB determines severity of sex-dependent acute liver injury.

Journal Article J Clin Invest · December 2, 2019 SH3 domain-binding protein that preferentially associates with Btk (SAB) is an outer-membrane docking protein for JNK-mediated impairment of mitochondrial function. Deletion of Sab in hepatocytes inhibits sustained JNK activation and cell death. The curren ... Full text Link to item Cite

The Natural History of Advanced Fibrosis Due to Nonalcoholic Steatohepatitis: Data From the Simtuzumab Trials.

Journal Article Hepatology · December 2019 Progression of nonalcoholic steatohepatitis (NASH) is incompletely characterized. We analyzed data on longitudinal changes in liver histology, hepatic venous pressure gradient (HVPG), and serum markers of fibrosis in 475 patients with NASH with bridging fi ... Full text Link to item Cite

A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH.

Journal Article Hepatol Commun · December 2019 A significantly higher proportion of patients with nonalcoholic steatohepatitis (NASH) who received obeticholic acid (OCA) had histological improvement relative to placebo in the FLINT (farnesoid X nuclear receptor ligand obeticholic acid for noncirrhotic, ... Full text Link to item Cite

Association of Histologic Disease Activity With Progression of Nonalcoholic Fatty Liver Disease.

Journal Article JAMA Netw Open · October 2, 2019 IMPORTANCE: The histologic evolution of the full spectrum of nonalcoholic fatty liver disease (NAFLD) and factors associated with progression or regression remain to be definitively established. OBJECTIVE: To evaluate the histologic evolution of NAFLD and ... Full text Link to item Cite

Exogenous PP2A inhibitor exacerbates the progression of nonalcoholic fatty liver disease via NOX2-dependent activation of miR21.

Journal Article Am J Physiol Gastrointest Liver Physiol · October 1, 2019 Nonalcoholic fatty liver disease (NAFLD) is an emerging global pandemic. Though significant progress has been made in unraveling the pathophysiology of the disease, the role of protein phosphatase 2A (PP2A) and its subsequent inhibition by environmental an ... Full text Link to item Cite

Validation of Serum Test for Advanced Liver Fibrosis in Patients With Nonalcoholic Steatohepatitis.

Journal Article Clin Gastroenterol Hepatol · August 2019 BACKGROUND & AIMS: We analyzed markers of fibrosis in serum samples from patients with nonalcoholic fatty liver disease (NAFLD), assessed by liver biopsy. We used serum levels of markers to develop an algorithm to discriminate patients with advanced fibros ... Full text Link to item Cite

Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage.

Journal Article Clin Gastroenterol Hepatol · August 2019 BACKGROUND & AIMS: Noninvasive methods are needed to determine disease stage in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the diagnostic performance of several widely available fibrosis models for the assessment of hepatic fibros ... Full text Link to item Cite

Nocturnal Hypoxia Activation of the Hedgehog Signaling Pathway Affects Pediatric Nonalcoholic Fatty Liver Disease Severity.

Journal Article Hepatol Commun · July 2019 Chronic intermittent hypoxia and hedgehog (Hh) pathway dysregulation are associated with nonalcoholic fatty liver disease (NAFLD) progression. In this study, we determined the relationship between obstructive sleep apnea (OSA)/nocturnal hypoxia and Hh sign ... Full text Link to item Cite

Dysregulated activation of fetal liver programme in acute liver failure.

Journal Article Gut · June 2019 OBJECTIVE: Uncertainty about acute liver failure (ALF) pathogenesis limits therapy. We postulate that ALF results from excessive reactivation of a fetal liver programme that is induced in hepatocytes when acutely injured livers regenerate. To evaluate this ... Full text Link to item Cite

Relationship between resolution of non-alcoholic steatohepatitis and changes in lipoprotein sub-fractions: a post-hoc analysis of the PIVENS trial.

Journal Article Aliment Pharmacol Ther · May 2019 BACKGROUND: Dyslipidaemia is frequent in non-alcoholic steatohepatitis (NASH); however, it is unclear if improvement in liver histology is associated with favourable changes in cardiovascular disease (CVD) risk. AIMS: To evaluate the relationship of NASH r ... Full text Link to item Cite

MicroRNA-375 Suppresses the Growth and Invasion of Fibrolamellar Carcinoma.

Journal Article Cell Mol Gastroenterol Hepatol · 2019 BACKGROUND & AIMS: Fibrolamellar carcinoma (FLC) is a rare liver cancer that primarily affects adolescents and young adults. It is characterized by a heterozygous approximately 400-kb deletion on chromosome 19 that results in a unique fusion between DnaJ h ... Full text Link to item Cite

Sparstolonin B (SsnB) attenuates liver fibrosis via a parallel conjugate pathway involving P53-P21 axis, TGF-beta signaling and focal adhesion that is TLR4 dependent.

Journal Article Eur J Pharmacol · December 15, 2018 SsnB previously showed a promising role to lessen liver inflammation observed in a mouse model of NAFLD. Since NAFLD can progress to fibrosis, studies were designed to unravel its role in attenuating NAFLD associated fibrosis. Using both in vivo and in vit ... Full text Link to item Cite

The conundrum of cryptogenic cirrhosis: Adverse outcomes without treatment options.

Journal Article J Hepatol · December 2018 BACKGROUND & AIMS: Although patients with cryptogenic cirrhosis have historically been considered as having "burnt-out" non-alcoholic steatohepatitis (NASH), some controversy remains. The aim of this study was to compare outcomes of patients with cryptogen ... Full text Link to item Cite

Microbial nitrogen limitation in the mammalian large intestine.

Journal Article Nat Microbiol · December 2018 Resource limitation is a fundamental factor governing the composition and function of ecological communities. However, the role of resource supply in structuring the intestinal microbiome has not been established and represents a challenge for mammals that ... Full text Link to item Cite

Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis.

Journal Article Sci Transl Med · November 21, 2018 Fibrosis is the major determinant of morbidity and mortality in patients with nonalcoholic steatohepatitis (NASH) but has no approved pharmacotherapy in part because of incomplete understanding of its pathogenic mechanisms. Here, we report that hepatocyte ... Full text Link to item Cite

Reply.

Journal Article Clin Gastroenterol Hepatol · October 2018 Full text Open Access Link to item Cite

Simtuzumab Is Ineffective for Patients With Bridging Fibrosis or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis.

Journal Article Gastroenterology · October 2018 BACKGROUND & AIMS: Lysyl oxidase-like 2 contributes to fibrogenesis by catalyzing cross-linkage of collagen. We evaluated the safety and efficacy of simtuzumab, a monoclonal antibody against lysyl oxidase-like 2, in two phase 2b trials of patients with adv ... Full text Link to item Cite

Liver regeneration requires Yap1-TGFβ-dependent epithelial-mesenchymal transition in hepatocytes.

Journal Article J Hepatol · August 2018 BACKGROUND & AIMS: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar tissue, ultimately resulting in cirrhosis. Therefore, defining and optimizing mec ... Full text Open Access Link to item Cite

Towards a definite mouse model of NAFLD.

Journal Article J Hepatol · August 2018 Full text Link to item Cite

High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease.

Journal Article Redox Biol · July 2018 High circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD) but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-medi ... Full text Link to item Cite

Markers of Tissue Repair and Cellular Aging Are Increased in the Liver Tissue of Patients With HIV Infection Regardless of Presence of HCV Coinfection.

Journal Article Open Forum Infect Dis · July 2018 Liver disease is a leading cause of HIV-related mortality. Hepatitis C virus (HCV)-related fibrogenesis is accelerated in the setting of HIV coinfection, yet the mechanisms underlying this aggressive pathogenesis are unclear. We identified formalin-fixed p ... Full text Open Access Link to item Cite

The hedgehog pathway in nonalcoholic fatty liver disease.

Journal Article Crit Rev Biochem Mol Biol · June 2018 Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of obesity-associated liver diseases and it has become the major cause of cirrhosis in the Western world. The high prevalence of NAFLD-associated advanced liver disease reflects both the high ... Full text Link to item Cite

Prometheus revisited.

Journal Article J Clin Invest · June 1, 2018 The liver's extraordinary ability to regenerate has been known since the myth of Prometheus, but the mechanisms involved are still being discovered. Various small animal models have been used in this quest. Two of the most popular include partial hepatecto ... Full text Link to item Cite

Fructose and sugar: A major mediator of non-alcoholic fatty liver disease.

Journal Article J Hepatol · May 2018 Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome; its rising prevalence parallels the rise in obesity and diabetes. Historically thought to result from overnutrition and a sedentary lifestyle, recent evidence sug ... Full text Link to item Cite

Hedgehog-YAP Signaling Pathway Regulates Glutaminolysis to Control Activation of Hepatic Stellate Cells.

Conference Gastroenterology · April 2018 BACKGROUND & AIMS: Cirrhosis results from accumulation of myofibroblasts derived from quiescent hepatic stellate cells (Q-HSCs); it regresses when myofibroblastic HSCs are depleted. Hedgehog signaling promotes transdifferentiation of HSCs by activating Yes ... Full text Link to item Cite

Hedgehog signalling in liver pathophysiology.

Journal Article J Hepatol · March 2018 Liver disease remains a leading cause of mortality worldwide despite recent successes in the field of viral hepatitis, because increases in alcohol consumption and obesity are fuelling an epidemic of chronic fatty liver disease for which there are currentl ... Full text Link to item Cite

Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic.

Journal Article Toxicol Sci · March 1, 2018 Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic, a Society of Toxicology Contemporary Concepts in Toxicology (CCT) workshop was held on March 11, 2017. The meeting was convened to raise awareness of metabolic syndrome and its assoc ... Full text Link to item Cite

The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: A randomized, phase 2 trial.

Journal Article Hepatology · February 2018 Inhibition of apoptosis signal-regulating kinase 1, a serine/threonine kinase, leads to improvement in inflammation and fibrosis in animal models of nonalcoholic steatohepatitis. We evaluated the safety and efficacy of selonsertib, a selective inhibitor of ... Full text Link to item Cite

DNA methylation signatures reflect aging in patients with nonalcoholic steatohepatitis.

Journal Article JCI Insight · January 25, 2018 A DNA methylation (DNAm) signature (the "Horvath clock") has been proposed as a measure of human chronological and biological age. We determined peripheral blood DNAm in patients with nonalcoholic steatohepatitis (NASH) and assessed whether accelerated agi ... Full text Link to item Cite

RNA Binding Proteins Control Transdifferentiation of Hepatic Stellate Cells into Myofibroblasts.

Journal Article Cell Physiol Biochem · 2018 BACKGROUND/AIMS: Myofibroblasts (MF) derived from quiescent nonfibrogenic hepatic stellate cells (HSC) are the major sources of fibrous matrix in cirrhosis. Because many factors interact to regulate expansion and regression of MF-HSC populations, efforts t ... Full text Link to item Cite

Branched chain amino acid transaminase 1 (BCAT1) is overexpressed and hypomethylated in patients with non-alcoholic fatty liver disease who experience adverse clinical events: A pilot study.

Journal Article PLoS One · 2018 BACKGROUND AND OBJECTIVES: Although the burden of non-alcoholic fatty liver disease (NAFLD) continues to increase worldwide, genetic factors predicting progression to cirrhosis and decompensation in NAFLD remain poorly understood. We sought to determine wh ... Full text Open Access Link to item Cite

Alcoholic liver disease

Chapter · January 1, 2018 Consumption of alcohol is common in adults, and modest consumption has reported health benefits; however, chronic daily alcohol consumption above recommended limits is an important cause of chronic liver disease and cirrhosis. The amount and duration of al ... Full text Cite

Developmental Morphogens & Recovery from Alcoholic Liver Disease.

Journal Article Adv Exp Med Biol · 2018 Alcohol-induced steatohepatitis (ASH) increases the risk for both clinically-severe acute alcoholic hepatitis and eventual cirrhosis. The mechanisms that control ASH pathogenesis and progression are unclear but processes that regulate liver cell plasticity ... Full text Link to item Cite

HMGB1-RAGE pathway drives peroxynitrite signaling-induced IBD-like inflammation in murine nonalcoholic fatty liver disease.

Journal Article Redox Biol · October 2017 Recent clinical studies found a strong association of colonic inflammation and Inflammatory bowel disease (IBD)-like phenotype with NonAlcoholic Fatty liver Disease (NAFLD) yet the mechanisms remain unknown. The present study identifies high mobility group ... Full text Link to item Cite

The diversity and plasticity of adult hepatic progenitor cells and their niche.

Journal Article Liver Int · September 2017 The liver is a unique organ for homoeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several fac ... Full text Open Access Link to item Cite

Association Between Cytokines and Liver Histology in Children with Nonalcoholic Fatty Liver Disease.

Journal Article Hepatol Commun · September 2017 BACKGROUND: Reliable non-invasive markers to characterize inflammation, hepatocellular ballooning, and fibrosis in nonalcoholic fatty liver disease (NAFLD) are lacking. We investigated the relationship between plasma cytokine levels and features of NAFLD h ... Full text Link to item Cite

Low and High Birth Weights Are Risk Factors for Nonalcoholic Fatty Liver Disease in Children.

Journal Article J Pediatr · August 2017 OBJECTIVES: To examine the distribution of birth weight in children with nonalcoholic fatty liver disease (NAFLD) compared with the general US population, and to investigate the relationship between birth weight and severity of NAFLD. STUDY DESIGN: A multi ... Full text Link to item Cite

Thymosin beta-4 regulates activation of hepatic stellate cells via hedgehog signaling.

Journal Article Sci Rep · June 19, 2017 The molecular mechanisms of thymosin beta-4 (TB4) involved in regulating hepatic stellate cell (HSC) functions remain unclear. Therefore, we hypothesize that TB4 influences HSC activation through hedgehog (Hh) pathway. HSC functions declined in a TB4 siRNA ... Full text Link to item Cite

Reply to Kim et al.

Journal Article Am J Gastroenterol · May 2017 Full text Link to item Cite

Loss of pericyte smoothened activity in mice with genetic deficiency of leptin.

Journal Article BMC Cell Biol · April 20, 2017 BACKGROUND: Obesity is associated with multiple diseases, but it is unclear how obesity promotes progressive tissue damage. Recovery from injury requires repair, an energy-expensive process that is coupled to energy availability at the cellular level. The ... Full text Open Access Link to item Cite

Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.

Journal Article J Immunol · April 15, 2017 Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent ... Full text Link to item Cite

Hypoxia of the growing liver accelerates regeneration.

Journal Article Surgery · March 2017 BACKGROUND: After portal vein ligation of 1 side of the liver, the other side regenerates at a slow rate. This slow growth may be accelerated to rapid growth by adding a transection between the 2 sides, i.e., performing portal vein ligation and parenchymal ... Full text Link to item Cite

Nonalcoholic Steatohepatitis.

Journal Article Annu Rev Med · January 14, 2017 Nonalcoholic steatohepatitis (NASH) has become a major cause of cirrhosis and liver-related deaths worldwide. NASH is strongly associated with obesity and the metabolic syndrome, conditions that cause lipid accumulation in hepatocytes (hepatic steatosis). ... Full text Link to item Cite

Timing Is Everything.

Journal Article Cell Metab · January 10, 2017 In a recent issue of Cancer Cell, Kettner and colleagues (2016) link disruption of normal circadian rhythms to NASH and associated liver cancer, suggesting that molecular clocks, as well as their regulators and target genes, might provide novel therapeutic ... Full text Link to item Cite

Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease.

Journal Article Hepatology · January 2017 UNLABELLED: Despite the high prevalence of nonalcoholic fatty liver disease (NAFLD), therapeutic options and noninvasive markers of disease activity and severity remain limited. We investigated the association between plasma biomarkers and liver histology ... Full text Link to item Cite

Patient Sex, Reproductive Status, and Synthetic Hormone Use Associate With Histologic Severity of Nonalcoholic Steatohepatitis.

Journal Article Clin Gastroenterol Hepatol · January 2017 BACKGROUND & AIMS: Sex and sex hormones can affect responses of patients with nonalcoholic fatty liver disease (NAFLD) to metabolic stress and development of hepatocyte injury and inflammation. METHODS: We collected data from 3 large U.S. studies of patien ... Full text Link to item Cite

TRPV4 activation of endothelial nitric oxide synthase resists nonalcoholic fatty liver disease by blocking CYP2E1-mediated redox toxicity.

Journal Article Free Radic Biol Med · January 2017 NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for e ... Full text Link to item Cite

Serum osteopontin is a biomarker of severe fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

Journal Article Int J Parasitol · December 2016 Schistosomiasis is a major cause of fibrosis and portal hypertension. The reason 4-10% of infected subjects develops hepatosplenic schistosomiasis remains unclear. Chronically infected male CBA/J mice reproduce the dichotomic forms of human schistosomiasis ... Full text Link to item Cite

Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms.

Journal Article Aliment Pharmacol Ther · December 2016 BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH). AIM: ... Full text Link to item Cite

Vitamin D is Not Associated With Severity in NAFLD: Results of a Paired Clinical and Gene Expression Profile Analysis.

Journal Article Am J Gastroenterol · November 2016 OBJECTIVES: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) is complex. Vitamin D (VitD) has been implicated in NAFLD pathogenesis because it has roles in immune modulation, cell differentiation and proliferation, and regulation of inflammatio ... Full text Link to item Cite

Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni.

Journal Article PLoS Negl Trop Dis · October 2016 BACKGROUND: Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully ... Full text Link to item Cite

Reply.

Journal Article Hepatology · September 2016 Full text Link to item Cite

Hedgehog regulates yes-associated protein 1 in regenerating mouse liver.

Conference Hepatology · July 2016 UNLABELLED: Adult liver regeneration requires induction and suppression of proliferative activity in multiple types of liver cells. The mechanisms that orchestrate the global changes in gene expression that are required for proliferative activity to change ... Full text Link to item Cite

A longer duration of estrogen deficiency increases fibrosis risk among postmenopausal women with nonalcoholic fatty liver disease.

Journal Article Hepatology · July 2016 UNLABELLED: Postmenopausal women with nonalcoholic steatohepatitis are at an increased risk of hepatic fibrosis compared with premenopausal women. Whether duration of estrogen deficiency in postmenopausal state dictates an individual's fibrosis risk remain ... Full text Link to item Cite

Pathogenesis of Nonalcoholic Steatohepatitis.

Journal Article Gastroenterology · June 2016 Nonalcoholic steatohepatitis (NASH) is a necro-inflammatory response that ensues when hepatocytes are injured by lipids (lipotoxicity). NASH is a potential outcome of nonalcoholic fatty liver (NAFL), a condition that occurs when lipids accumulate in hepato ... Full text Link to item Cite

Role of Hedgehog Signaling Pathway in NASH.

Journal Article Int J Mol Sci · June 1, 2016 Non-alcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease in the Western world. Although only a minority of patients will ultimately develop end-stage liver disease, it is not yet possible to efficiently predict who will pr ... Full text Link to item Cite

Nonalcoholic Fatty Liver Disease and the Gut Microbiome.

Journal Article Clin Liver Dis · May 2016 Recent progress has allowed a more comprehensive study of the gut microbiota. Gut microbiota helps in health maintenance and gut dysbiosis associates with chronic metabolic diseases. Modulation of short-chain fatty acids and choline bioavailability, lipopr ... Full text Link to item Cite

Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

Journal Article Cancer Res · April 15, 2016 Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results hav ... Full text Link to item Cite

Pleiotrophin regulates the ductular reaction by controlling the migration of cells in liver progenitor niches.

Journal Article Gut · April 2016 OBJECTIVE: The ductular reaction (DR) involves mobilisation of reactive-appearing duct-like cells (RDC) along canals of Hering, and myofibroblastic (MF) differentiation of hepatic stellate cells (HSC) in the space of Disse. Perivascular cells in stem cell ... Full text Open Access Link to item Cite

Sparstolonin B attenuates early liver inflammation in experimental NASH by modulating TLR4 trafficking in lipid rafts via NADPH oxidase activation.

Journal Article Am J Physiol Gastrointest Liver Physiol · April 1, 2016 Although significant research data exist on the pathophysiology of nonalcoholic steatohepatitis (NASH), finding an efficient treatment regimen for it remains elusive. The present study used sparstolonin B (SsnB), a novel TLR4 antagonist derived from the Ch ... Full text Link to item Cite

Reply.

Journal Article Hepatology · March 2016 Full text Link to item Cite

Systematic transcriptome analysis reveals elevated expression of alcohol-metabolizing genes in NAFLD livers.

Journal Article J Pathol · March 2016 Obese animals and non-alcoholic fatty liver disease (NAFLD) patients exhibit elevated blood alcohol, suggesting potential contributions of alcohol metabolism to the development of NAFLD. Liver gene expression in patients with biopsy-proven mild (N = 40) an ... Full text Link to item Cite

The severity of nonalcoholic fatty liver disease is associated with gut dysbiosis and shift in the metabolic function of the gut microbiota.

Journal Article Hepatology · March 2016 UNLABELLED: Several animal studies have emphasized the role of gut microbiota in nonalcoholic fatty liver disease (NAFLD). However, data about gut dysbiosis in human NAFLD remain scarce in the literature, especially studies including the whole spectrum of ... Full text Link to item Cite

Caspase-2 promotes obesity, the metabolic syndrome and nonalcoholic fatty liver disease.

Journal Article Cell Death Dis · February 18, 2016 Obesity and its resulting metabolic disturbances are major health threats. In response to energy surplus, overtaxed adipocytes release fatty acids and pro-inflammatory factors into the circulation, promoting organ fat accumulation (including nonalcoholic f ... Full text Link to item Cite

Purinergic receptor X7 mediates leptin induced GLUT4 function in stellate cells in nonalcoholic steatohepatitis.

Journal Article Biochim Biophys Acta · January 2016 Metabolic oxidative stress via CYP2E1 can act as a second hit in NASH progression. Our previous studies have shown that oxidative stress in NASH causes higher leptin levels and induces purinergic receptor X7 (P2X7r). We tested the hypothesis that higher ci ... Full text Link to item Cite

Vitamin B5 and N-Acetylcysteine in Nonalcoholic Steatohepatitis: A Preclinical Study in a Dietary Mouse Model.

Journal Article Dig Dis Sci · January 2016 BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the number one cause of chronic liver disease and second indication for liver transplantation in the Western world. Effective therapy is still not available. Previously we showed a critical role for c ... Full text Link to item Cite

Osteopontin is a proximal effector of leptin-mediated non-alcoholic steatohepatitis (NASH) fibrosis.

Journal Article Biochim Biophys Acta · January 2016 INTRODUCTION: Liver fibrosis develops when hepatic stellate cells (HSC) are activated into collagen-producing myofibroblasts. In non-alcoholic steatohepatitis (NASH), the adipokine leptin is upregulated, and promotes liver fibrosis by directly activating H ... Full text Link to item Cite

Liver injury-on-a-chip: microfluidic co-cultures with integrated biosensors for monitoring liver cell signaling during injury.

Journal Article Lab Chip · December 7, 2015 Tissue injury triggers complex communication between cells via secreted signaling molecules such as cytokines and growth factors. Discerning when and where these signals begin and how they propagate over time is very challenging with existing cell culture ... Full text Link to item Cite

Ductal metaplasia in oesophageal submucosal glands is associated with inflammation and oesophageal adenocarcinoma.

Journal Article Histopathology · December 2015 AIMS: Recent studies have suggested that oesophageal submucosal gland (ESMG) ducts harbour progenitor cells that may contribute to oesophageal metaplasia. Our objective was to determine whether histological differences exist between the ESMGs of individual ... Full text Link to item Cite

Dysregulated metabolism contributes to oncogenesis.

Journal Article Semin Cancer Biol · December 2015 Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic proce ... Full text Link to item Cite

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Journal Article Semin Cancer Biol · December 2015 Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most ... Full text Link to item Cite

Schistosome-induced cholangiocyte proliferation and osteopontin secretion correlate with fibrosis and portal hypertension in human and murine schistosomiasis mansoni.

Journal Article Clin Sci (Lond) · November 2015 Schistosomiasis is a major cause of portal hypertension worldwide. It associates with portal fibrosis that develops during chronic infection. The mechanisms by which the pathogen evokes these host responses remain unclear. We evaluated the hypothesis that ... Full text Open Access Link to item Cite

LGR5 is associated with tumor aggressiveness in papillary thyroid cancer.

Journal Article Oncotarget · October 27, 2015 PURPOSE: Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with ... Full text Link to item Cite

Accumulation of duct cells with activated YAP parallels fibrosis progression in non-alcoholic fatty liver disease.

Journal Article J Hepatol · October 2015 BACKGROUND & AIMS: Mechanisms that regulate regeneration of injured livers are complex. YAP, a stem cell associated factor, controls liver growth in healthy adult mice. Increasing nuclear localization of YAP triggers accumulation of reactive-appearing duct ... Full text Link to item Cite

Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.

Journal Article Sci Rep · September 28, 2015 Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical ... Full text Link to item Cite

Hedgehog signaling in the liver

Chapter · September 28, 2015 The Hedgehog signaling pathway regulates tissue patterning during development. Because it is barely active in healthy adult livers, the Hedgehog pathway was generally presumed to be irrelevant in adult livers. However, that dogma was shattered by the demon ... Full text Cite

Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice.

Journal Article Gut · July 2015 BACKGROUND: Chronic liver injury triggers a progenitor cell repair response, and liver fibrosis occurs when repair becomes deregulated. Previously, we reported that reactivation of the hedgehog pathway promotes fibrogenic liver repair. Osteopontin (OPN) is ... Full text Link to item Cite

Reduced lipoapoptosis, hedgehog pathway activation and fibrosis in caspase-2 deficient mice with non-alcoholic steatohepatitis.

Journal Article Gut · July 2015 OBJECTIVE: Caspase-2 is an initiator caspase involved in multiple apoptotic pathways, particularly in response to specific intracellular stressors (eg, DNA damage, ER stress). We recently reported that caspase-2 was pivotal for the induction of cell death ... Full text Link to item Cite

NADPH Oxidase-Derived Peroxynitrite Drives Inflammation in Mice and Human Nonalcoholic Steatohepatitis via TLR4-Lipid Raft Recruitment.

Journal Article Am J Pathol · July 2015 The molecular events that link NADPH oxidase activation and the induction of Toll-like receptor (TLR)-4 recruitment into hepatic lipid rafts in nonalcoholic steatohepatitis (NASH) are unclear. We hypothesized that in liver, NADPH oxidase activation is key ... Full text Link to item Cite

Fibrosis in nonalcoholic Fatty liver disease: mechanisms and clinical implications.

Journal Article Semin Liver Dis · May 2015 Nonalcoholic fatty liver disease (NAFLD) is tightly associated with obesity and the metabolic syndrome in the United States and other Western countries. It is also the liver disease most rapidly increasing in prevalence in the United States, and has become ... Full text Link to item Cite

Reply: To PMID 24849310.

Journal Article Hepatology · May 2015 Full text Link to item Cite

Prometheus and progenitors.

Journal Article Hepatology · April 2015 Full text Link to item Cite

Inflammatory models drastically alter tumor growth and the immune microenvironment in hepatocellular carcinoma.

Journal Article Sci Bull (Beijing) · April 1, 2015 Initiation and progression of hepatocellular carcinoma (HCC) is intimately associated with a chronically diseased liver tissue. This diseased liver tissue background is a drastically different microenvironment from the healthy liver, especially with regard ... Full text Link to item Cite

Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial.

Journal Article Lancet · March 14, 2015 BACKGROUND: The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticho ... Full text Link to item Cite

Role of Fn14 in acute alcoholic steatohepatitis in mice.

Journal Article Am J Physiol Gastrointest Liver Physiol · February 15, 2015 TNF-like weak inducer of apoptosis (TWEAK) is a growth factor for bipotent liver progenitors that express its receptor, fibroblast growth factor-inducible 14 (Fn14), a TNF receptor superfamily member. Accumulation of Fn14(+) progenitors occurs in severe ac ... Full text Link to item Cite

Micro-RNA 21 inhibition of SMAD7 enhances fibrogenesis via leptin-mediated NADPH oxidase in experimental and human nonalcoholic steatohepatitis.

Journal Article Am J Physiol Gastrointest Liver Physiol · February 15, 2015 Hepatic fibrosis in nonalcoholic steatohepatitis (NASH) is the common pathophysiological process resulting from chronic liver inflammation and oxidative stress. Although significant research has been carried out on the role of leptin-induced NADPH oxidase ... Full text Link to item Cite

Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity.

Journal Article Hepatology · January 2015 UNLABELLED: Hedgehog (Hh) ligand production by ballooned hepatocytes drives nonalcoholic steatohepatitis (NASH) progression in mice. The NIDDK-sponsored PIVENS trial (NCT00063622) showed that vitamin E (VitE) improved NASH. We investigated whether VitE tre ... Full text Link to item Cite

M1 polarization bias and subsequent nonalcoholic steatohepatitis progression is attenuated by nitric oxide donor DETA NONOate via inhibition of CYP2E1-induced oxidative stress in obese mice.

Journal Article J Pharmacol Exp Ther · January 2015 Activation of M1 macrophages in nonalcoholic steatohepatitis (NASH) is produced by several external or endogenous factors: inflammatory stimuli, oxidative stress, and cytokines are known. However, any direct role of oxidative stress in causing M1 polarizat ... Full text Link to item Cite

Elaboration of tubules with active hedgehog drives parenchymal fibrogenesis in gestational alloimmune liver disease.

Journal Article Hum Pathol · January 2015 Gestational alloimmune liver disease (GALD) produces severe neonatal liver disease that is notable for paucity of hepatocytes, large numbers of parenchymal tubules, and extensive fibrosis. Liver specimens from 19 GALD cases were studied in comparison with ... Full text Link to item Cite

Upregulation of miR21 and repression of Grhl3 by leptin mediates sinusoidal endothelial injury in experimental nonalcoholic steatohepatitis.

Journal Article PLoS One · 2015 Sinusoidal endothelial dysfunction (SED) has been found to be an early event in nonalcoholic steatohepatitis (NASH) progression but the molecular mechanisms underlying its causation remains elusive. We hypothesized that adipokine leptin worsens sinusoidal ... Full text Link to item Cite

Mouse models of diet-induced nonalcoholic steatohepatitis reproduce the heterogeneity of the human disease.

Journal Article PLoS One · 2015 BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH), the potentially progressive form of nonalcoholic fatty liver disease (NAFLD), is the pandemic liver disease of our time. Although there are several animal models of NASH, consensus regarding the op ... Full text Link to item Cite

Animal models of nonalcoholic fatty liver disease

Chapter · January 1, 2015 Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, accompanying the rise in obesity and its related metabolic disorders. Though research in the field is vibrant, enormous gaps in knowledge still remain about its ... Full text Cite

Role of Developmental Morphogens in Liver Regeneration

Chapter · January 1, 2015 Hedgehog is a morphogen that regulates tissue patterning during development. In the fetal liver, the Hedgehog pathway is active in progenitor cells, arresting such cells in an immature phenotype. Hence, the pathway must be inhibited for progenitors to diff ... Full text Cite

Repair-related activation of hedgehog signaling in stromal cells promotes intrahepatic hypothyroidism.

Journal Article Endocrinology · November 2014 Thyroid hormone (TH) is important for tissue repair because it regulates cellular differentiation. Intrahepatic TH activity is controlled by both serum TH levels and hepatic deiodinases. TH substrate (T4) is converted into active hormone (T3) by deiodinase ... Full text Link to item Cite

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome.

Journal Article World J Gastroenterol · October 21, 2014 Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance (IR), early diabetes, hypertension and dyslipidemia. Recent studies have ... Full text Link to item Cite

Abstract 4117: Utilizing RNA aptamers for biomarker discovery in a novel cell culture system for hepatocellular carcinoma

Conference Cancer Research · October 1, 2014 AbstractIntroduction: Current serum biomarkers for hepatocellular carcinoma (HCC) lack the sensitivity and specificity to be effective screening tools. Aptamers are single-stranded RNA oligonucleotides that ... Full text Cite

Reply: To PMID 23913408.

Journal Article Hepatology · October 2014 Full text Link to item Cite

The β-adrenoceptor agonist isoproterenol rescues acetaminophen-injured livers through increasing progenitor numbers by Wnt in mice.

Journal Article Hepatology · September 2014 UNLABELLED: Acetaminophen (APAP)-induced acute liver injury (AILI) is a major health problem. Accumulating evidence suggests that the sympathetic nervous system (SNS) regulates neuronal and hematopoietic progenitors. SNS signaling affects hepatic progenito ... Full text Link to item Cite

Myofibroblastic cells function as progenitors to regenerate murine livers after partial hepatectomy.

Journal Article Gut · August 2014 OBJECTIVE: Smoothened (SMO), a coreceptor of the Hedgehog (Hh) pathway, promotes fibrogenic repair of chronic liver injury. We investigated the roles of SMO+ myofibroblast (MF) in liver regeneration by conditional deletion of SMO in α smooth muscle actin ( ... Full text Link to item Cite

Iron deficiency in patients with nonalcoholic Fatty liver disease is associated with obesity, female gender, and low serum hepcidin.

Journal Article Clin Gastroenterol Hepatol · July 2014 BACKGROUND & AIMS: Iron deficiency is often observed in obese individuals. The iron regulatory hormone hepcidin is regulated by iron and cytokines interleukin (IL) 6 and IL1β. We examine the relationship between obesity, circulating levels of hepcidin, and ... Full text Link to item Cite

Osteopontin is up-regulated in chronic hepatitis C and is associated with cellular permissiveness for hepatitis C virus replication.

Journal Article Clin Sci (Lond) · June 2014 OPN (osteopontin)) is a Hh (Hedgehog)-regulated cytokine that is up-regulated during chronic liver injury and directly promotes fibrosis. We have reported that Hh signalling enhances viral permissiveness and replication in HCV (hepatitis C virus)-infected ... Full text Link to item Cite

Gender and menopause impact severity of fibrosis among patients with nonalcoholic steatohepatitis.

Conference Hepatology · April 2014 UNLABELLED: Estrogens inhibit stellate cell activation and fibrogenesis. Thus, gender and reproductive states may influence the degree of fibrosis in patients with nonalcoholic steatohepatitis (NASH). To investigate the association between gender, menopaus ... Full text Link to item Cite

Reply: To PMID 23978500.

Journal Article Clin Gastroenterol Hepatol · March 2014 Full text Link to item Cite

Alcohol activates the hedgehog pathway and induces related procarcinogenic processes in the alcohol-preferring rat model of hepatocarcinogenesis.

Journal Article Alcohol Clin Exp Res · March 2014 BACKGROUND: Alcohol consumption promotes hepatocellular carcinoma (HCC). The responsible mechanisms are not well understood. Hepatocarcinogenesis increases with age and is enhanced by factors that impose a demand for liver regeneration. Because alcohol is ... Full text Link to item Cite

Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease.

Journal Article Hepatology · February 2014 UNLABELLED: Clinicians rely upon the severity of liver fibrosis to segregate patients with well-compensated nonalcoholic fatty liver disease (NAFLD) into subpopulations at high- versus low-risk for eventual liver-related morbidity and mortality. We compare ... Full text Link to item Cite

Potential role of Hedgehog signaling and microRNA-29 in liver fibrosis of IKKβ-deficient mouse.

Journal Article J Mol Histol · February 2014 Recent studies have reported that NF-κB mediated down-regulation of miRNA-29 and lower expression of miRNA-29 promoted the deposition of collagens in fibrotic liver. Our previous research demonstrated that the increased Hedgehog (Hh) signaling, a key regul ... Full text Link to item Cite

CYP2E1-dependent and leptin-mediated hepatic CD57 expression on CD8+ T cells aid progression of environment-linked nonalcoholic steatohepatitis.

Journal Article Toxicol Appl Pharmacol · January 1, 2014 Environmental toxins induce a novel CYP2E1/leptin signaling axis in liver. This in turn activates a poorly characterized innate immune response that contributes to nonalcoholic steatohepatitis (NASH) progression. To identify the relevant subsets of T-lymph ... Full text Link to item Cite

Liver renewal: detecting misrepair and optimizing regeneration.

Journal Article Mayo Clin Proc · January 2014 UNLABELLED: Cirrhosis and liver cancer, the main causes of liver-related morbidity and mortality, result from defective repair of liver injury. This article summarizes rapidly evolving knowledge about liver myofibroblasts and progenitors, the 2 key cell ty ... Full text Link to item Cite

TWEAK/Fn14 signaling is required for liver regeneration after partial hepatectomy in mice.

Journal Article PLoS One · 2014 BACKGROUND & AIMS: Pro-inflammatory cytokines are important for liver regeneration after partial hepatectomy (PH). Expression of Fibroblast growth factor-inducible 14 (Fn14), the receptor for TNF-like weak inducer of apoptosis (TWEAK), is induced rapidly a ... Full text Open Access Link to item Cite

Evidence for and against epithelial-to-mesenchymal transition in the liver.

Journal Article Am J Physiol Gastrointest Liver Physiol · December 2013 The outcome of liver injury is determined by the success of repair. Liver repair involves replacement of damaged liver tissue with healthy liver epithelial cells (including both hepatocytes and cholangiocytes) and reconstruction of normal liver structure a ... Full text Link to item Cite

Purinergic receptor X7 is a key modulator of metabolic oxidative stress-mediated autophagy and inflammation in experimental nonalcoholic steatohepatitis.

Journal Article Am J Physiol Gastrointest Liver Physiol · December 2013 Recent studies indicate that metabolic oxidative stress, autophagy, and inflammation are hallmarks of nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanisms that link these important events in NASH remain unclear. In this study, ... Full text Link to item Cite

Cross-talk between Notch and Hedgehog regulates hepatic stellate cell fate in mice.

Journal Article Hepatology · November 2013 UNLABELLED: Liver repair involves phenotypic changes in hepatic stellate cells (HSCs) and reactivation of morphogenic signaling pathways that modulate epithelial-to-mesenchymal/mesenchymal-to-epithelial transitions, such as Notch and Hedgehog (Hh). Hh stim ... Full text Link to item Cite

Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease.

Journal Article Gastroenterology · November 2013 BACKGROUND & AIMS: Cirrhosis and liver cancer are potential outcomes of advanced nonalcoholic fatty liver disease (NAFLD). It is not clear what factors determine whether patients will develop advanced or mild NAFLD, limiting noninvasive diagnosis and treat ... Full text Link to item Cite

MicroRNA expression differentiates squamous epithelium from Barrett's esophagus and esophageal cancer.

Journal Article Dig Dis Sci · November 2013 BACKGROUND: Current strategies fail to identify most patients with esophageal adenocarcinoma (EAC) before the disease becomes advanced and incurable. Given the dismal prognosis associated with EAC, improvements in detection of early-stage esophageal neopla ... Full text Link to item Cite

NAFLD, NASH and liver cancer.

Journal Article Nat Rev Gastroenterol Hepatol · November 2013 NAFLD affects a large proportion of the US population and its incidence and prevalence are increasing to epidemic proportions around the world. As with other liver diseases that cause cirrhosis, NAFLD increases the risk of liver cancer, a disease with poor ... Full text Link to item Cite

STAT3-mediated attenuation of CCl4-induced mouse liver fibrosis by the protein kinase inhibitor sorafenib.

Journal Article J Autoimmun · October 2013 There have been major advances in defining the immunological events associated with fibrosis in various chronic liver diseases. We have taken advantage of this data to focus on the mechanisms of action of a unique multi-kinase inhibitor, coined sorafenib, ... Full text Link to item Cite

Hedgehog signaling in human medullary thyroid carcinoma: a novel signaling pathway.

Journal Article Thyroid · September 2013 BACKGROUND: Locally or widely metastatic medullary thyroid carcinoma (MTC) is difficult to treat, and therapeutic options are limited. Recently, kinase inhibitors have shown partial efficacy in this cancer, but there is a continued need for the development ... Full text Link to item Cite

Associations of depression, anxiety and antidepressants with histological severity of nonalcoholic fatty liver disease.

Journal Article Liver Int · August 2013 BACKGROUND: Depression and anxiety are common in patients with nonalcoholic fatty liver disease (NAFLD). However, their associations with histological severity of NAFLD are unknown. AIM: This study examined the association(s) of depression, anxiety and ant ... Full text Link to item Cite

Environmental toxin-linked nonalcoholic steatohepatitis and hepatic metabolic reprogramming in obese mice.

Journal Article Toxicol Sci · August 2013 Obesity is associated with strong risks of development of chronic inflammatory liver disease and metabolic syndrome following a second hit. This study tests the hypothesis that free radical metabolism of low chronic exposure to bromodichloromethane (BDCM), ... Full text Link to item Cite

Smoothened is a master regulator of adult liver repair.

Journal Article J Clin Invest · June 2013 When regenerative processes cannot keep pace with cell death, functional epithelia are replaced by scar. Scarring is characterized by both excessive accumulation of fibrous matrix and persistent outgrowth of cell types that accumulate transiently during su ... Full text Link to item Cite

Hedgehog pathway and pediatric nonalcoholic fatty liver disease.

Journal Article Hepatology · May 2013 UNLABELLED: It is unclear why the histology of pediatric and adult nonalcoholic fatty liver disease (NAFLD) sometimes differs. In adults, severity of portal inflammation and fibrosis correlate with Hedgehog pathway activity. Hedgehog (Hh) signaling regulat ... Full text Link to item Cite

Underlying potential: cellular and molecular determinants of adult liver repair.

Journal Article J Clin Invest · May 2013 The liver has a unique and extraordinary capacity for regeneration, even in adult organisms. This regenerative potential has traditionally been attributed to the replicative capabilities of mature hepatocytes and cholangiocytes, though emerging evidence su ... Full text Link to item Cite

Genetic signatures in choline and 1-carbon metabolism are associated with the severity of hepatic steatosis.

Journal Article FASEB J · April 2013 Choline metabolism is important for very low-density lipoprotein secretion, making this nutritional pathway an important contributor to hepatic lipid balance. The purpose of this study was to assess whether the cumulative effects of multiple single nucleot ... Full text Link to item Cite

Leptin is key to peroxynitrite-mediated oxidative stress and Kupffer cell activation in experimental non-alcoholic steatohepatitis.

Journal Article J Hepatol · April 2013 BACKGROUND & AIMS: Progression from steatosis to steatohepatitic lesions is hypothesized to require a second hit. These lesions have been associated with increased oxidative stress, often ascribed to high levels of leptin and other proinflammatory mediator ... Full text Link to item Cite

Biochemistry of Liver Regeneration

Chapter · February 15, 2013 Epithelial injury stimulates repair mechanisms that replace dead epithelial cells in various adult organs, including the liver. Unlike other organs, however, the liver is capable of efficiently reconstructing the entire tissue without scarring (i.e., regen ... Full text Cite

Hedgehog signalling regulates liver sinusoidal endothelial cell capillarisation.

Journal Article Gut · February 2013 OBJECTIVE: Vascular remodelling during liver damage involves loss of healthy liver sinusoidal endothelial cell (LSEC) phenotype via capillarisation. Hedgehog (Hh) signalling regulates vascular development and increases during liver injury. This study there ... Full text Link to item Cite

Macrophage-derived Hedgehog ligands promotes fibrogenic and angiogenic responses in human schistosomiasis mansoni.

Journal Article Liver Int · January 2013 BACKGROUND: Schistosomiasis mansoni is a major cause of portal fibrosis and portal hypertension. The Hedgehog pathway regulates fibrogenic repair in some types of liver injury. AIMS: Determine if Hedgehog pathway activation occurs during fibrosis progressi ... Full text Link to item Cite

The benefits of restraint: a pivotal role for IL-13 in hepatic glucose homeostasis.

Journal Article J Clin Invest · January 2013 In response to feeding, insulin promotes the uptake of sugar in peripheral tissues and suppresses the production of sugar, a process called gluconeogenesis, in the liver. Recent research has shown that chronic inflammation promotes insulin resistance, and ... Full text Link to item Cite

Paracrine Hedgehog signaling drives metabolic changes in hepatocellular carcinoma.

Journal Article Cancer Res · December 15, 2012 Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that s ... Full text Link to item Cite

Alcoholic liver disease

Journal Article · December 1, 2012 Full text Cite

Hedgehog signaling blockade delays hepatocarcinogenesis induced by hepatitis B virus X protein.

Journal Article Cancer Res · November 15, 2012 The hepatitis B virus (HBV) encoded X protein (HBx) contributes centrally to the pathogenesis of hepatocellular carcinoma (HCC). Aberrant activation of the Hedgehog (Hh) pathway has been linked to many tumor types including HCC. Thus, experiments were desi ... Full text Link to item Cite

Hedgehog controls hepatic stellate cell fate by regulating metabolism.

Journal Article Gastroenterology · November 2012 BACKGROUND & AIMS: The pathogenesis of cirrhosis, a disabling outcome of defective liver repair, involves deregulated accumulation of myofibroblasts derived from quiescent hepatic stellate cells (HSCs), but the mechanisms that control transdifferentiation ... Full text Link to item Cite

Lower serum hepcidin and greater parenchymal iron in nonalcoholic fatty liver disease patients with C282Y HFE mutations.

Journal Article Hepatology · November 2012 UNLABELLED: Hepcidin regulation is linked to both iron and inflammatory signals and may influence iron loading in nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the relationships among HFE genotype, serum hepcidin level, hepatic ... Full text Link to item Cite

Relationship between adipose tissue insulin resistance and liver histology in nonalcoholic steatohepatitis: a pioglitazone versus vitamin E versus placebo for the treatment of nondiabetic patients with nonalcoholic steatohepatitis trial follow-up study.

Journal Article Hepatology · October 2012 UNLABELLED: The PIVENS (Pioglitazone versus Vitamin E versus Placebo for the Treatment of Nondiabetic Patients with Nonalcoholic Steatohepatitis [NASH]) trial demonstrated that pioglitazone and vitamin E improved liver histology to varying degrees, but the ... Full text Link to item Cite

Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines.

Journal Article BMC Cancer · September 10, 2012 BACKGROUND: Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluat ... Full text Link to item Cite

NKT-associated hedgehog and osteopontin drive fibrogenesis in non-alcoholic fatty liver disease.

Journal Article Gut · September 2012 OBJECTIVE: Immune responses are important in dictating non-alcoholic steatohepatitis (NASH) outcome. We previously reported that upregulation of hedgehog (Hh) and osteopontin (OPN) occurs in NASH, that Hh-regulated accumulation of natural killer T (NKT) ce ... Full text Link to item Cite

Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes.

Journal Article Hepatology · September 2012 UNLABELLED: Fructose consumption predicts increased hepatic fibrosis in those with nonalcoholic fatty liver disease (NAFLD). Because of its ability to lower hepatic adenosine triphosphate (ATP) levels, habitual fructose consumption could result in more hep ... Full text Link to item Cite

Mechanisms of disease progression in NASH: new paradigms.

Journal Article Clin Liver Dis · August 2012 The incidence of nonalcoholic fatty liver disease is increasing at an astonishing rate in the US population. Although only a small proportion of these patients develop steatohepatitis (NASH), those who do have a greater likelihood of developing end-stage l ... Full text Link to item Cite

Association between puberty and features of nonalcoholic fatty liver disease.

Journal Article Clin Gastroenterol Hepatol · July 2012 BACKGROUND & AIMS: Physiological changes that occur during puberty might affect pathologic features of nonalcoholic fatty liver disease (NAFLD). We investigated associations between pubertal development and clinical and histopathologic features of NAFLD. M ... Full text Link to item Cite

Costaining for keratins 8/18 plus ubiquitin improves detection of hepatocyte injury in nonalcoholic fatty liver disease.

Journal Article Hum Pathol · June 2012 Nonalcoholic fatty liver disease is a global health dilemma. The gold standard for diagnosis is liver biopsy. Ballooned hepatocytes are histologic manifestations of hepatocellular injury and are characteristic of steatohepatitis, the more severe form of no ... Full text Link to item Cite

Hedgehog pathway activation parallels histologic severity of injury and fibrosis in human nonalcoholic fatty liver disease.

Journal Article Hepatology · June 2012 UNLABELLED: The Hedgehog (HH)-signaling pathway mediates several processes that are deregulated in patients with metabolic syndrome (e.g., fat mass regulation, vascular/endothelial remodeling, liver injury and repair, and carcinogenesis). The severity of n ... Full text Link to item Cite

Diabetes and the Liver

Journal Article · April 19, 2012 Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in the western world. The syndrome encompasses a spectrum of histopathological changes in the liver ranging from benign fatty infiltration (steatosis) to steatosis w ... Full text Cite

Choline intake in a large cohort of patients with nonalcoholic fatty liver disease.

Journal Article Am J Clin Nutr · April 2012 BACKGROUND: There is significant histologic and biochemical overlap between nonalcoholic fatty liver disease (NAFLD) and steatohepatitis associated with choline deficiency. OBJECTIVE: We sought to determine whether subjects with biopsy-proven NAFLD and evi ... Full text Link to item Cite

Correlation of vitamin E, uric acid, and diet composition with histologic features of pediatric NAFLD.

Journal Article J Pediatr Gastroenterol Nutr · January 2012 OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children in the United States. Although changes in diet are often recommended to improve NAFLD, little is known regarding the influence of diet on histologic f ... Full text Link to item Cite

Up-regulation of Hedgehog pathway is associated with cellular permissiveness for hepatitis C virus replication.

Journal Article Hepatology · November 2011 UNLABELLED: Studies of the hepatitis C virus (HCV) life-cycle rely heavily on Huh7.5 cells, but the reasons why these cells are exceptionally permissive for HCV replication are not clear. Based on recent clinical observations, we hypothesized that the Hedg ... Full text Link to item Cite

Noninvasive evaluation of hepatic fibrosis using acoustic radiation force-based shear stiffness in patients with nonalcoholic fatty liver disease.

Journal Article J Hepatol · September 2011 BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease in developed countries, may progress to nonalcoholic steatohepatitis (NASH) in a minority of people. Those with NASH are at increased risk for cirrho ... Full text Link to item Cite

Increased production of sonic hedgehog by ballooned hepatocytes.

Journal Article J Pathol · July 2011 Ballooned hepatocytes distinguish non-alcoholic steatohepatitis (NASH) from steatosis. Such cells contain dilated endoplasmic reticulum and ubiquitin aggregates, characteristics of endoplasmic reticulum stress. Hepatocyte ballooning increases the risk for ... Full text Link to item Cite

Pathogenesis of alcohol-induced liver disease: classical concepts and recent advances.

Journal Article J Gastroenterol Hepatol · July 2011 Alcoholic liver disease (ALD) is a primary consequence of heavy and prolonged drinking. ALD contributes to the bulk of liver disease burden worldwide. Progression of ALD is a multifactorial and multistep process that includes many genetic and environmental ... Full text Link to item Cite

Hedgehog signaling in cholangiocytes.

Journal Article Curr Opin Gastroenterol · May 2011 PURPOSE OF REVIEW: Cells lining the biliary tree are targets of injury, but also orchestrate liver repair. The latter involves autocrine/paracrine signaling that enhances the viability and growth of residual ductular cells and promotes accumulation of infl ... Full text Link to item Cite

Hedgehog activity, epithelial-mesenchymal transitions, and biliary dysmorphogenesis in biliary atresia.

Journal Article Hepatology · April 2011 UNLABELLED: Biliary atresia (BA) is notable for marked ductular reaction and rapid development of fibrosis. Activation of the Hedgehog (Hh) pathway promotes the expansion of populations of immature epithelial cells that coexpress mesenchymal markers and ma ... Full text Link to item Cite

Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease.

Journal Article Am J Gastroenterol · March 2011 OBJECTIVES: Factors that determine disease severity in nonalcoholic fatty liver disease (NAFLD) are unclear, but exercise is a recommended treatment. We evaluated the association between physical activity intensity and histological severity of NAFLD. METHO ... Full text Link to item Cite

Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits.

Journal Article PLoS Genet · March 2011 Nonalcoholic fatty liver disease (NAFLD) clusters in families, but the only known common genetic variants influencing risk are near PNPLA3. We sought to identify additional genetic variants influencing NAFLD using genome-wide association (GWA) analysis of ... Full text Link to item Cite

Hedgehog signaling in the liver.

Journal Article J Hepatol · February 2011 Reactivation of Hedgehog (Hh), a morphogenic signaling pathway that controls progenitor cell fate and tissue construction during embryogenesis occurs during many types of liver injury in adult. The net effects of activating the Hedgehog pathway include exp ... Full text Link to item Cite

Paracrine modulation of cholangiocyte serotonin synthesis orchestrates biliary remodeling in adults.

Journal Article Am J Physiol Gastrointest Liver Physiol · February 2011 Paracrine signaling between cholangiocytes and stromal cells regulates biliary remodeling. Cholangiocytes have neuroepithelial characteristics and serotonin receptor agonists inhibit their growth, but whether they are capable of serotonin biosynthesis is u ... Full text Link to item Cite

The role of Hedgehog signaling in fibrogenic liver repair.

Journal Article Int J Biochem Cell Biol · February 2011 Repair of adult liver, like many tissues, involves the coordinated response of a number of different cell types. In adult livers, fibroblastic cells, ductular cells, inflammatory cells, and progenitor cells contribute to this process. Our studies demonstra ... Full text Link to item Cite

Osteopontin is induced by hedgehog pathway activation and promotes fibrosis progression in nonalcoholic steatohepatitis.

Journal Article Hepatology · January 2011 UNLABELLED: Nonalcoholic steatohepatitis (NASH) is a leading cause of cirrhosis. Recently, we showed that NASH-related cirrhosis is associated with Hedgehog (Hh) pathway activation. The gene encoding osteopontin (OPN), a profibrogenic extracellular matrix ... Full text Link to item Cite

Hedgehog signaling antagonist promotes regression of both liver fibrosis and hepatocellular carcinoma in a murine model of primary liver cancer.

Journal Article PLoS One · 2011 OBJECTIVE: Chronic fibrosing liver injury is a major risk factor for hepatocarcinogenesis in humans. Mice with targeted deletion of Mdr2 (the murine ortholog of MDR3) develop chronic fibrosing liver injury. Hepatocellular carcinoma (HCC) emerges spontaneou ... Full text Open Access Link to item Cite

Cancer stem cells: repair gone awry?

Journal Article J Oncol · 2011 Because cell turnover occurs in all adult organs, stem/progenitor cells within the stem-cell niche of each tissue must be appropriately mobilized and differentiated to maintain normal organ structure and function. Tissue injury increases the demands on thi ... Full text Link to item Cite

Sonic hedgehog pathway

Journal Article · December 1, 2010 The Hedgehog (Hh) Pathway, originally identified in Drosophila, [1-4] is a highly conserved signaling pathway which orchestrates multiple, disparate aspects of embryogenesis, development and tissue remodeling in a wide spectrum of systems [5-8]. This is us ... Full text Cite

Viral factors induce Hedgehog pathway activation in humans with viral hepatitis, cirrhosis, and hepatocellular carcinoma.

Journal Article Lab Invest · December 2010 Hedgehog (Hh) pathway activation promotes many processes that occur during fibrogenic liver repair. Whether the Hh pathway modulates the outcomes of virally mediated liver injury has never been examined. Gene-profiling studies of human hepatocellular carci ... Full text Open Access Link to item Cite

Regional anthropometric measures and hepatic fibrosis in patients with nonalcoholic Fatty liver disease.

Journal Article Clin Gastroenterol Hepatol · December 2010 BACKGROUND & AIMS: In overnourished individuals, impaired peripheral fat storage (ie, reduced fat mass in extremities) can increase delivery of surplus calories to the organs other than peripheral adipose tissues, including the liver (ie, lipid overload), ... Full text Link to item Cite

Leptin promotes the myofibroblastic phenotype in hepatic stellate cells by activating the hedgehog pathway.

Journal Article J Biol Chem · November 19, 2010 Trans-differentiation of quiescent hepatic stellate cells (Q-HSCs), which exhibit epithelial and adipocytic features, into myofibroblastic-HSC (MF-HSCs) is a key event in liver fibrosis. Culture models demonstrated that Hedgehog (Hh) pathway activation is ... Full text Link to item Cite

Effect of a 12-month intensive lifestyle intervention on hepatic steatosis in adults with type 2 diabetes.

Journal Article Diabetes Care · October 2010 OBJECTIVE: Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven. RESEARCH DESIGN AND METHODS: Look AHEAD (Action for Health in Diabetes) is a 1 ... Full text Link to item Cite

Clinical, laboratory and histological associations in adults with nonalcoholic fatty liver disease.

Journal Article Hepatology · September 2010 UNLABELLED: The Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) was formed to conduct multicenter studies on the etiology, contributing factors, natural history, and treatment of nonalcoholic steatohepatitis (NASH). The aim of this study ... Full text Link to item Cite

Activation of Rac1 promotes hedgehog-mediated acquisition of the myofibroblastic phenotype in rat and human hepatic stellate cells.

Journal Article Hepatology · July 2010 UNLABELLED: Hepatic accumulation of myofibroblastic hepatic stellate cells (MF-HSCs) is pivotal in the pathogenesis of cirrhosis. Two events are necessary for MF-HSCs to accumulate in damaged livers: transition of resident, quiescent hepatic stellate cells ... Full text Link to item Cite

Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease.

Journal Article Hepatology · June 2010 UNLABELLED: Liver inflammation is greater in nonalcoholic steatohepatitis (NASH) than steatosis, suggesting that immune responses contribute to nonalcoholic fatty liver disease (NAFLD) progression. Livers normally contain many natural killer T (NKT) cells ... Full text Link to item Cite

Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver disease.

Journal Article Hepatology · June 2010 UNLABELLED: The rising incidence of obesity and diabetes coincides with a marked increase in fructose consumption. Fructose consumption is higher in individuals with nonalcoholic fatty liver disease (NAFLD) than in age-matched and body mass index (BMI)-mat ... Full text Link to item Cite

Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis.

Journal Article N Engl J Med · May 6, 2010 BACKGROUND: Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis. Currently, there is no established treatment for this disease. METHODS: We randomly assigned 247 adults with nonalcoholic steatohepatitis and without diabete ... Full text Link to item Cite

Hedgehog signaling is critical for normal liver regeneration after partial hepatectomy in mice.

Journal Article Hepatology · May 2010 UNLABELLED: Distinct mechanisms are believed to regulate growth of the liver during fetal development and after injury in adults, because the former relies on progenitors and the latter generally involves replication of mature hepatocytes. However, chronic ... Full text Link to item Cite

Signals from dying hepatocytes trigger growth of liver progenitors.

Journal Article Gut · May 2010 OBJECTIVE: The death rate of mature hepatocytes is chronically increased in various liver diseases, triggering responses that prevent liver atrophy, but often cause fibrosis. Mice with targeted disruption of inhibitor kappa B kinase (Ikk) in hepatocytes (H ... Full text Link to item Cite

Epithelial-mesenchymal transitions and hepatocarcinogenesis.

Journal Article J Clin Invest · April 2010 Epithelial-mesenchymal transitions (EMTs) are believed to play a role in invasion and metastasis of many types of tumors. In this issue of the JCI, Chen et al. show that a gene that has been associated with aggressive biology in hepatocellular carcinomas i ... Full text Open Access Link to item Cite

Genetic susceptibility to hepatic steatosis.

Journal Article N Engl J Med · March 25, 2010 Full text Link to item Cite

Hepatic complications of obesity.

Journal Article Gastroenterol Clin North Am · March 2010 Obesity is associated with a spectrum of chronic liver disease. Because obesity increases the risk for advanced forms of liver disease (ie, cirrhosis and liver cancer), the obesity epidemic is emerging as a major factor underlying the burden of liver disea ... Full text Link to item Cite

Serum aminotransferase changes with significant weight loss: sex and age effects.

Journal Article Metabolism · February 2010 In obese subjects, the liver may be differentially affected by significant weight loss depending on as yet unknown factors. We explored clinical factors associated with serum alanine aminotransferase (ALT) changes during significant weight loss in a reside ... Full text Link to item Cite

Paradoxical Effects of Smo Proto-Oncogene Overexpression in Hepatocytes

Conference ANNALS OF SURGICAL ONCOLOGY · February 1, 2010 Link to item Cite

Treatment of nonalcoholic fatty liver disease in children: TONIC trial design.

Journal Article Contemp Clin Trials · January 2010 BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) in children can lead to steatohepatitis, cirrhosis, and end-stage liver disease. The cause of NAFLD is unknown, but it is commonly associated with obesity, insulin resistance, and dyslipidemia. OBJECTIVE ... Full text Link to item Cite

Non-alcoholic steatohepatitis pathogenesis: role of repair in regulating the disease progression.

Journal Article Dig Dis · 2010 BACKGROUND: Increased hepatocyte apoptosis distinguishes non-alcoholic steatohepatitis (NASH) from non-alcoholic fatty liver disease (NAFLD). Therefore, we postulated that outcomes of NASH depended upon whether or not hepatic regenerative responses could k ... Full text Link to item Cite

Hedgehog pathway activation and epithelial-to-mesenchymal transitions during myofibroblastic transformation of rat hepatic cells in culture and cirrhosis.

Journal Article Am J Physiol Gastrointest Liver Physiol · December 2009 Myofibroblastic hepatic stellate cells (MF-HSC) are derived from quiescent hepatic stellate cells (Q-HSC). Q-HSC express certain epithelial cell markers and have been reported to form junctional complexes similar to epithelial cells. We have shown that Hed ... Full text Link to item Cite

Epithelial-to-mesenchymal transitions in the liver.

Journal Article Hepatology · December 2009 The outcome of liver injury is dictated by the effectiveness of repair. Successful repair (i.e., regeneration) results in replacement of dead epithelial cells with healthy epithelial cells, and reconstructs normal hepatic structure and function. Liver rege ... Full text Link to item Cite

Domain 3 of hepatitis C virus core protein is sufficient for intracellular lipid accumulation.

Journal Article J Infect Dis · December 1, 2009 BACKGROUND: Hepatitis C virus (HCV) is a major cause of liver disease worldwide, with steatosis, or "fatty liver," being a frequent histologic finding. In previous work, we identified sequence polymorphisms within domain 3 (d3) of genotype 3 HCV core prote ... Full text Link to item Cite

Apoptosis and cytokines in non-alcoholic steatohepatitis.

Journal Article Clin Liver Dis · November 2009 Non-alcoholic fatty liver disease (NAFLD), one of the commonest causes of chronic liver disease in the United States, represents several overlapping clinicopathological states, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Although ... Full text Link to item Cite

Pan-caspase inhibitor VX-166 reduces fibrosis in an animal model of nonalcoholic steatohepatitis.

Journal Article Hepatology · November 2009 UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a potentially progressive liver disease that culminates in cirrhosis. Cirrhosis occurs more often in individuals with nonalcoholic steatohepatitis (NASH) than in those with steatosis (nonalcoholic fat ... Full text Link to item Cite

Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease.

Journal Article Clin Gastroenterol Hepatol · October 2009 BACKGROUND & AIMS: There is a need for a reliable and inexpensive noninvasive marker of hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the performance of the FIB4 index (based on age, aspartate aminotransferase [AST ... Full text Link to item Cite

Hedgehog-mediated epithelial-to-mesenchymal transition and fibrogenic repair in nonalcoholic fatty liver disease.

Journal Article Gastroenterology · October 2009 BACKGROUND & AIMS: Repair responses define the ultimate outcomes of liver disease. This study evaluated the hypothesis that fibrogenic repair in nonalcoholic fatty liver disease (NAFLD) is mediated by Hedgehog (Hh) pathway activation and consequent inducti ... Full text Link to item Cite

In vivo quantification of liver stiffness in a rat model of hepatic fibrosis with acoustic radiation force.

Journal Article Ultrasound Med Biol · October 2009 Liver fibrosis is currently staged using needle biopsy, a highly invasive procedure with a number of disadvantages. Measurement of liver stiffness changes that accompany progression of the disease may provide a quantitative and noninvasive method to assess ... Full text Link to item Cite

Genetic differences in oxidative stress and inflammatory responses to diet-induced obesity do not alter liver fibrosis in mice.

Journal Article Liver Int · September 2009 OBJECTIVE: To determine how genetic factors might influence the progression of nonalcoholic fatty liver disease (NAFLD). DESIGN/INTERVENTION: Beginning in adolescence, male C57BL6 (BL6) and 129/SVJ mice were fed control (n=15/group) or high-fat (HF) diets ... Full text Link to item Cite

Repair-related activation of hedgehog signaling promotes cholangiocyte chemokine production.

Journal Article Hepatology · August 2009 UNLABELLED: The mechanisms mediating hepatic accumulation of inflammatory cells in cholestatic liver disease remain enigmatic. Our thesis is that Hedgehog (Hh) pathway activation promotes hepatic accumulation of immune cells that interact with cholangiocyt ... Full text Link to item Cite

Activation of glycolysis and apoptosis in glycogen storage disease type Ia.

Journal Article Mol Genet Metab · August 2009 The deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia, growth retardation, renal fai ... Full text Link to item Cite

Co-medications that modulate liver injury and repair influence clinical outcome of acetaminophen-associated liver injury.

Journal Article Clin Gastroenterol Hepatol · August 2009 BACKGROUND & AIMS: Acetaminophen-induced liver injury is the most common cause of acute liver failure in the United States; it occurs inadvertently in approximately half of all cases. Concomitant use of other medications might impact susceptibility to acet ... Full text Link to item Cite

Role for hedgehog pathway in regulating growth and function of invariant NKT cells.

Journal Article Eur J Immunol · July 2009 Lymphocyte accumulation is characteristic of chronic hepatitis, but the mechanisms regulating lymphocyte numbers and their roles in liver disease progression are poorly understood. The Hedgehog (Hh) pathway regulates thymic development and lymphopoeisis du ... Full text Link to item Cite

Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network.

Journal Article Hepatology · June 2009 UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The association between NAFLD and quality of life (QOL) remains unclear. These data are important to estimate the burden of illness in NAFLD ... Full text Link to item Cite

REGULATION OF PROGENITOR RESPONSE TO ALCOHOL-INDUCED LIVER INJURY

Journal Article ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH · June 1, 2009 Link to item Cite

Similarities and differences in the pathogenesis of alcoholic and nonalcoholic steatohepatitis.

Journal Article Semin Liver Dis · May 2009 Subpopulations of individuals with alcohol-induced fatty livers and nonalcoholic steatosis develop steatohepatitis. Steatohepatitis is defined histologically: increased numbers of injured and dying hepatocytes distinguish this condition from simple steatos ... Full text Link to item Cite

Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network.

Journal Article Hepatology · March 2009 UNLABELLED: Adult nonalcoholic fatty liver disease (NAFLD) is characterized by absent or mild portal chronic inflammation (CI); in children, portal CI may be predominant. This study correlated clinical features with portal CI. Centrally-graded biopsies and ... Full text Link to item Cite

Sonic hedgehog ligand partners with caveolin-1 for intracellular transport.

Journal Article Lab Invest · March 2009 Prenatal alcohol exposure is the most common environmental factor leading to congenital birth defects in the United States. Although significant progress has been made in this field, the detailed molecular pathology of fetal alcohol syndrome (FAS) remains ... Full text Link to item Cite

Recruitment of host progenitor cells in rat liver transplants.

Journal Article Hepatology · February 2009 Despite major histocompatibility complex incompatibility, liver transplants from Lewis rats to dark agouti (DA) rats survive indefinitely without immunosuppression, and the studies we report sought the mechanism(s) responsible for this. At 1 year, most of ... Full text Link to item Cite

Novel Mutant Smoothened in Hepatomas Can Activate Hedgehog Signaling

Journal Article ANNALS OF SURGICAL ONCOLOGY · February 1, 2009 Link to item Cite

Liver cell-derived microparticles activate hedgehog signaling and alter gene expression in hepatic endothelial cells.

Journal Article Gastroenterology · January 2009 BACKGROUND & AIMS: Angiogenesis contributes to vascular remodeling during cirrhosis. In cirrhotic livers, cholangiocytes, and myofibroblastic hepatic stellate cells (MF-HSC) produce Hedgehog (Hh) ligands. During embryogenesis Hh ligands are released from l ... Full text Link to item Cite

Analysis of Hepatic Progenitor Populations in Methyl Deficient Liver Injury

Journal Article ANNALS OF SURGICAL ONCOLOGY · 2009 Cite

A genomic approach to colon cancer risk stratification yields biologic insights into therapeutic opportunities.

Journal Article Proc Natl Acad Sci U S A · December 9, 2008 Gene expression profiles provide an opportunity to dissect the heterogeneity of solid tumors, including colon cancer, to improve prognosis and predict response to therapies. Bayesian binary regression methods were used to generate a signature of disease re ... Full text Link to item Cite

Clinical correlates of histopathology in pediatric nonalcoholic steatohepatitis.

Journal Article Gastroenterology · December 2008 BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver disease in American children. Noninvasive means to discriminate between NAFLD and nonalcoholic steatohepatitis (NASH) might diminish the requirement for liver biopsy or ... Full text Link to item Cite

Mechanisms of disease progression in nonalcoholic fatty liver disease.

Journal Article Semin Liver Dis · November 2008 Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic pathology, ranging from simple steatosis (also called nonalcoholic fatty liver or NAFL) in its most benign form, to cirrhosis in its most advanced form. Nonalcoholic steatohepatitis ... Full text Link to item Cite

Hedgehog signaling regulates epithelial-mesenchymal transition during biliary fibrosis in rodents and humans.

Journal Article J Clin Invest · October 2008 Epithelial-mesenchymal transitions (EMTs) play an important role in tissue construction during embryogenesis, and evidence suggests that this process may also help to remodel some adult tissues after injury. Activation of the hedgehog (Hh) signaling pathwa ... Full text Link to item Cite

The hedgehog pathway regulates remodelling responses to biliary obstruction in rats.

Journal Article Gut · September 2008 Featured Publication BACKGROUND: Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following biliary decompression, suggesting that it may also be involved in the repair of biliary damage. The hedgeh ... Full text Link to item Cite

Fate-mapping evidence that hepatic stellate cells are epithelial progenitors in adult mouse livers.

Journal Article Stem Cells · August 2008 Featured Publication Liver injury activates quiescent hepatic stellate cells (Q-HSC) to proliferative myofibroblasts. Accumulation of myofibroblastic hepatic stellate cells (MF-HSC) sometimes causes cirrhosis and liver failure. However, MF-HSC also promote liver regeneration b ... Full text Link to item Cite

Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

Journal Article Curr Opin Lipidol · June 2008 PURPOSE OF REVIEW: Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride ... Full text Link to item Cite

Fructose consumption as a risk factor for non-alcoholic fatty liver disease.

Journal Article J Hepatol · June 2008 Featured Publication BACKGROUND/AIMS: While the rise in non-alcoholic fatty liver disease (NAFLD) parallels the increase in obesity and diabetes, a significant increase in dietary fructose consumption in industrialized countries has also occurred. The increased consumption of ... Full text Link to item Cite

Hepatic fat and adenosine triphosphate measurement in overweight and obese adults using 1H and 31P magnetic resonance spectroscopy.

Journal Article Liver Int · May 2008 Featured Publication BACKGROUND/AIMS: Magnetic resonance spectroscopy (MRS) measures hepatic fat and adenosine triphosphate (ATP), but magnetic resonance studies are challenging in obese subjects. We aimed to evaluate the inter- and intrarater reliability and stability of hepa ... Full text Link to item Cite

Accumulation of hedgehog-responsive progenitors parallels alcoholic liver disease severity in mice and humans.

Journal Article Gastroenterology · May 2008 Featured Publication BACKGROUND & AIMS: Improving outcomes in alcoholic liver disease (ALD) necessitates better understanding of how habitual ethanol (EtOH) consumption alters normal regenerative mechanisms within the liver. Hedgehog (Hh) pathway activation promotes expansion ... Full text Link to item Cite

Regulation of the Liver Cell Mass

Journal Article · April 15, 2008 Full text Cite

The adventures of sonic hedgehog in development and repair. II. Sonic hedgehog and liver development, inflammation, and cancer.

Journal Article Am J Physiol Gastrointest Liver Physiol · March 2008 Featured Publication Hedgehog (Hh) signaling modulates tissue remodeling by controlling the fate of Hh-responsive cells. Healthy adult livers exhibit little Hh activity. However, cells involved in adult liver repair, including myofibroblasts and progenitors, are capable of pro ... Full text Link to item Cite

Diacylglycerol acyltranferase 1 anti-sense oligonucleotides reduce hepatic fibrosis in mice with nonalcoholic steatohepatitis.

Journal Article Hepatology · February 2008 Featured Publication UNLABELLED: Retinyl ester (RE) stores decrease during hepatic stellate cell (HSC) activation and liver fibrosis. Although retinol esterification is mostly catalyzed by lecithin:retinol acyltransferase (LRAT), diacylglycerol acyltransferase (DGAT)1 also doe ... Full text Link to item Cite

Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation.

Journal Article J Infect Dis · January 15, 2008 BACKGROUND: Steatosis is a common histological finding and a poor prognostic indicator in patients with hepatitis C virus (HCV) infection. In HCV genotype 3-infected patients, the etiology of steatosis appears to be closely correlated with unknown viral fa ... Full text Link to item Cite

Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells.

Journal Article J Hepatol · January 2008 Featured Publication BACKGROUND/AIMS: Factors released during liver injury, such as platelet derived growth factor-BB (PDGF), promote accumulation of myofibroblastic hepatic stellate cells (MFB) that drive the pathogenesis of cirrhosis. The hedgehog (Hh) pathway regulates remo ... Full text Link to item Cite

The effect of a probiotic on hepatic steatosis.

Journal Article J Clin Gastroenterol · 2008 Full text Link to item Cite

Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging.

Journal Article Int J Obes (Lond) · January 2008 OBJECTIVE: To examine five available software packages for the assessment of abdominal adipose tissue with magnetic resonance imaging, compare their features and assess the reliability of measurement results. DESIGN: Feature evaluation and test-retest reli ... Full text Link to item Cite

Role of immune response in nonalcoholic fatty liver disease: Evidence in human and animal studies

Journal Article · December 1, 2007 Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic pathology ranging from nonalcoholic fatty liver (NAFL; steatosis) at the most clinically benign end of the spectrum to cirrhosis at the opposite extreme, where most liver-related morbidity a ... Full text Cite

Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice.

Journal Article Lab Invest · December 2007 Featured Publication Progenitors regenerate fatty livers but the mechanisms involved are uncertain. The Hedgehog pathway regulates mesendodermal progenitors and modulates mesenchymal-epithelial interactions during tissue remodeling. To determine if Hedgehog signaling increases ... Full text Link to item Cite

Dependence of in vivo, radiation force derived hepatic shear modulus estimates on imaging approach: Intercostal vs. subcostal

Journal Article Proceedings - IEEE Ultrasonics Symposium · December 1, 2007 The speed at which shear waves propagate can be used to quantify the shear modulus of tissue. Focused, impulsive, acoustic radiation force excitations can be used to generate transient displacement fields in soft tissue that create shear waves that propaga ... Full text Cite

In-vivo staging of liver fibrosis in a rat model using acoustic radiation force

Journal Article Proceedings - IEEE Ultrasonics Symposium · December 1, 2007 Liver fibrosis is currently staged using needle biopsy, a highly invasive procedure with a number of disadvantages. Measurement of liver stiffness changes which accompany progression of the disease may provide a quantitative and noninvasive method to asses ... Full text Cite

Nonalcoholic fatty liver disease as a complication of insulin resistance.

Journal Article Med Clin North Am · November 2007 Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis, advanced fibrosis, and rarely, progression to cirrhosis. The pathogenesis of NAFLD is thought to be related to insu ... Full text Link to item Cite

Targeting hedgehog signaling in medulloblastoma

Conference NEURO-ONCOLOGY · October 1, 2007 Link to item Cite

Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers.

Journal Article Lab Invest · September 2007 The liver regulates lipid homeostasis and is enriched with natural killer T (NKT) cells that respond to lipid antigens. Optimal maturation and activation of NKT cells requires their interaction with lipid antigens that are presented by cluster of different ... Full text Link to item Cite

De novo nonalcoholic fatty liver disease after liver transplantation.

Journal Article Liver Transpl · June 2007 Featured Publication Full text Link to item Cite

Inhibiting triglyceride synthesis improves hepatic steatosis but exacerbates liver damage and fibrosis in obese mice with nonalcoholic steatohepatitis.

Journal Article Hepatology · June 2007 Featured Publication UNLABELLED: In the early stages of nonalcoholic fatty liver disease (NAFLD), triglycerides accumulate in hepatocytes. Diacylglycerol acyltransferase 2 (DGAT2) catalyzes the final step in hepatocyte triglyceride biosynthesis. DGAT2 antisense oligonucleotide ... Full text Link to item Cite

Hedgehog-mediated mesenchymal-epithelial interactions modulate hepatic response to bile duct ligation.

Journal Article Lab Invest · May 2007 In bile duct-ligated (BDL) rodents, as in humans with chronic cholangiopathies, biliary obstruction triggers proliferation of bile ductular cells that are surrounded by fibrosis produced by adjacent myofibroblastic cells in the hepatic mesenchyme. The prox ... Full text Link to item Cite

Bile ductules and stromal cells express hedgehog ligands and/or hedgehog target genes in primary biliary cirrhosis.

Journal Article Hepatology · May 2007 Featured Publication UNLABELLED: Indian Hedgehog (Ihh) regulates tissue morphogenesis. Hedgehog (Hh) activity has been demonstrated in human cholangiocarcinoma and hepatocellular carcinoma lines, and in myofibroblasts and progenitors from adult rodent livers. We evaluated Hh p ... Full text Link to item Cite

Fetal alcohol exposure impairs Hedgehog cholesterol modification and signaling.

Journal Article Lab Invest · March 2007 Featured Publication Consumption of alcohol by pregnant women can cause fetal alcohol spectrum defects (FASD), a congenital disease, which is characterized by an array of developmental defects that include neurological, craniofacial, cardiac, and limb malformations, as well as ... Full text Link to item Cite

Mechanisms underlying nonalcoholic steatohepatitis

Journal Article Drug Discovery Today: Disease Mechanisms · December 1, 2006 Nonalcoholic fatty liver disease (NAFLD), a spectrum of liver damage, encompasses steatosis, steatohepatitis, an intermediate stage of liver disease and cirrhosis. Although NAFLD is the leading cause of chronic liver disease, no effective therapies current ... Full text Cite

PPARgamma agonists prevent TGFbeta1/Smad3-signaling in human hepatic stellate cells.

Journal Article Biochem Biophys Res Commun · November 17, 2006 Featured Publication PPARgamma agonists inhibit liver fibrosis, but the mechanisms involved are uncertain. We hypothesized that PPARgamma agonists inhibit transforming growth factor (TGF)beta1-activation of TGFbeta receptor (TGFbetaR)-1 signaling in quiescent stellate cells, t ... Full text Link to item Cite

Sustained activation of Rac1 in hepatic stellate cells promotes liver injury and fibrosis in mice.

Journal Article Hepatology · November 2006 Rac, a small, GTP-binding protein in the Rho family, regulates several cellular functions, including the activation of NADPH oxidase, a major intracellular producer of reactive oxygen species (ROS). Hepatic stellate cells (HSCs) isolated from mice that are ... Full text Link to item Cite

Evidence for epithelial-mesenchymal transitions in adult liver cells.

Journal Article Am J Physiol Gastrointest Liver Physiol · October 2006 Featured Publication Both myofibroblastic hepatic stellate cells (HSC) and hepatic epithelial progenitors accumulate in damaged livers. In some injured organs, the ability to distinguish between fibroblastic and epithelial cells is sometimes difficult because cells undergo epi ... Full text Link to item Cite

Interleukin-15 increases hepatic regenerative activity.

Journal Article J Hepatol · September 2006 BACKGROUND/AIMS: Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. However, IL-15's roles in liver are unknown. We aimed to determine if IL-15 influences hepatic in ... Full text Link to item Cite

Hedgehog signaling maintains resident hepatic progenitors throughout life.

Journal Article Am J Physiol Gastrointest Liver Physiol · May 2006 Hedgehog signaling through its receptor, Patched, activates transcription of genes, including Patched, that regulate the fate of various progenitors. Although Hedgehog signaling is required for endodermal commitment and hepatogenesis, the possibility that ... Full text Link to item Cite

Nonalcoholic steatohepatitis and nonalcoholic Fatty liver disease in young women with polycystic ovary syndrome.

Journal Article J Clin Endocrinol Metab · May 2006 Featured Publication CONTEXT: Nonalcoholic fatty liver disease and polycystic ovary syndrome (PCOS) are both associated with insulin resistance. Thus, women with PCOS may have an increased prevalence of nonalcoholic fatty liver disease, including nonalcoholic steatohepatitis ( ... Full text Link to item Cite

Dysregulation of the Hedgehog pathway in human hepatocarcinogenesis.

Journal Article Carcinogenesis · April 2006 Hedgehog (Hh) pathway activation promotes tumors in several endodermally derived tissues, but its role in the pathogenesis of hepatocellular carcinoma (HCC) is unknown. Although normal hepatocytes lack Hh signaling, activation of the Hh pathway in endoderm ... Full text Link to item Cite

Abnormal exhaled ethane concentrations in scleroderma.

Journal Article Biomarkers · 2006 Scleroderma (systemic sclerosis) is a chronic multisystem autoimmune disease in which oxidative stress is suspected to play a role in the pathophysiology. Therefore, it was postulated that patients with scleroderma would have abnormally high breath ethane ... Full text Link to item Cite

Breath biomarkers and non-alcoholic fatty liver disease: preliminary observations.

Journal Article Biomarkers · 2006 Breath biomarkers have the potential to offer information that is similar to conventional clinical tests or they are entirely unique. Preliminary data support the use of breath biomarkers in the study of liver disease, in particular non-alcoholic fatty liv ... Full text Link to item Cite

Role of insulin resistance and extrahepatic signalling in fatty liver disease

Conference Disease Progression and Disease Prevention in Hepatology and Gastroenterology · January 1, 2006 Link to item Cite

Role of inflammation in nonalcoholic steatohepatitis.

Journal Article Curr Opin Gastroenterol · November 2005 PURPOSE OF REVIEW: Products of hepatic macrophages and lymphocytes are acknowledged regulators of liver injury and repair. Recent studies have identified inflammatory modulators from sources within and outside the liver that are critical to the pathogenesi ... Full text Link to item Cite

Role for hedgehog signaling in hepatic stellate cell activation and viability.

Journal Article Lab Invest · November 2005 Hepatic stellate cells (HSC) have a complex phenotype that includes both neural and myofibroblastic features. The Hedgehog (Hh) pathway has been shown to direct the fate of neural and myofibroblastic cells during embryogenesis and during tissue remodeling ... Full text Link to item Cite

Lessons from animal models of NASH.

Journal Article Hepatol Res · October 2005 Studies of animals with obesity-related liver disease have taught us much about the mechanisms that mediate this pathology. Our work with genetically obese, insulin-resistant ob/ob mice demonstrates that hepatocytes become steatotic and die at increased ra ... Full text Link to item Cite

Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease.

Journal Article Hepatology · October 2005 Dietary factors promote obesity and obesity-related disorders, such as fatty liver disease. Natural killer T (NKT) cells are components of the innate immune system that regulate proinflammatory (Th-1) and anti-inflammatory (Th-2) immune responses. Previous ... Full text Link to item Cite

Insulin resistance and steatosis in hepatitis C virus infection.

Journal Article Gut · July 2005 The relationship between hepatitis C virus (HCV), steatosis, and insulin resistance is genotype specific, and steatosis and insulin resistance are closely linked to the progression of liver disease in HCV infected patients. ... Full text Link to item Cite

Roux-en-Y gastric bypass improves liver histology in patients with non-alcoholic fatty liver disease.

Journal Article Obes Res · July 2005 OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in the United States and is prevalent in morbidly obese patients. While weight loss and treatment of risk factors are recommended, the reported effects of baria ... Full text Link to item Cite

Hepatic 31P magnetic resonance spectroscopy: a hepatologist's user guide.

Journal Article Liver Int · June 2005 Hepatic phosphorus magnetic resonance spectroscopy (31P MRS) offers the exciting potential of studying metabolic processes in the human liver in vivo. Many investigators have utilized 31P MRS to research a broad range of metabolic questions, and there is o ... Full text Link to item Cite

A zebrafish model of Fetal Alcohol Syndrome parallels Hedgehog signaling defects

Conference ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH · May 1, 2005 Link to item Cite

Hepatic angiomyolipoma and hepatic stellate cells share a similar gene expression profile.

Journal Article Hum Pathol · April 2005 BACKGROUND AND AIMS: Angiomyolipomas (AMLs) of the liver are rare neoplasms composed of large epithelioid cells with intermixed fat and blood vessels. Hepatic AMLs have no clear normal-cell counterpart in the liver. However, AMLs and stellate cells both ar ... Full text Link to item Cite

Hepatic complications of obesity.

Journal Article Gastroenterol Clin North Am · March 2005 Obesity increases the risk and severity of liver disease. The most common form of liver disease that occurs in obesity is NAFLD. A better understanding of the basic disease mechanisms and natural histories ofNAFLD is needed to guide management and treatmen ... Full text Link to item Cite

Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients.

Journal Article Surg Obes Relat Dis · 2005 PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is a common and potentially serious form of chronic liver disease. Although NAFLD is known to be associated with obesity and some comorbid conditions, less is known about the severity of NAFLD among differe ... Full text Link to item Cite

Recent events in alcoholic liver disease V. effects of ethanol on liver regeneration.

Journal Article Am J Physiol Gastrointest Liver Physiol · January 2005 Liver regeneration is necessary to recover from alcoholic liver injury. Herein, we review evidence that ethanol interferes with liver regeneration. Briefly, alcoholic fatty livers demonstrate increased rates of hepatocyte death. The latter provides a regen ... Full text Link to item Cite

Arterial homeostasis, inflammation, and erythropoietic growth factors.

Journal Article Rev Cardiovasc Med · 2005 A neurohumoral link between kidneys and the heart has been established, particularly in the context of hypertension and cardiomyopathy. Beyond this neuro-endocrine pathway, another connecting system theoretically recruits growth factors that are selectivel ... Link to item Cite

Oxidative DNA damage and DNA repair enzyme expression are inversely related in murine models of fatty liver disease.

Journal Article Am J Physiol Gastrointest Liver Physiol · November 2004 Mitochondrial generation of reactive oxygen species (ROS) is increased in mice with fatty livers induced by genetic obesity, chronic consumption of ethanol, or methionine/choline-deficient diets. Both nuclear and mitochondrial (mt) DNA are targets for ROS- ... Full text Link to item Cite

Dietary composition and nonalcoholic fatty liver disease.

Journal Article Dig Dis Sci · October 2004 Nonalcoholic fatty liver disease (NAFLD) is a common and potentially serious form of chronic liver disease that occurs in patients who do not abuse alcohol. Present dietary recommendations for all Americans, including those with NAFLD, endorse a low-calori ... Full text Link to item Cite

Sympathetic nervous system regulation of liver repair.

Journal Article Anat Rec A Discov Mol Cell Evol Biol · September 2004 This chapter reviews recent evidence that the sympathetic nervous system (SNS) regulates liver repair by modulating the phenotypes of hepatic stellate cells (HSCs), the liver's principal fibrogenic cells, and hepatic epithelial progenitors, i.e., oval cell ... Full text Link to item Cite

Obesity and alcoholic liver disease.

Journal Article Alcohol · August 2004 Obesity potentiates the severity of alcohol-induced liver damage. Ethanol influences adipose tissue production of hormones and cytokines. The mechanisms by which adiposity and ethanol interact to produce hepatic steatosis and steatohepatitis are beginning ... Full text Link to item Cite

Tumor necrosis factor and its potential role in insulin resistance and nonalcoholic fatty liver disease.

Journal Article Clin Liver Dis · August 2004 Nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic pathology that resembles alcohol-induced fatty liver disease(AFLD), but which develops in individuals who are not heavy drinkers. In people, NAFLD is associated strongly with obesity,insulin ... Full text Link to item Cite

Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis.

Journal Article Hepatology · August 2004 It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activi ... Full text Link to item Cite

Overexpression of caspase-3 in hepatocellular carcinomas.

Journal Article Mod Pathol · July 2004 Caspase-3 is a downstream effector cysteine protease in the apoptotic pathway. It is ubiquitously expressed in normal human tissues including the liver. Overexpression and loss of expression of caspase-3 has been reported in diverse human malignancies. How ... Full text Link to item Cite

Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial.

Journal Article Aliment Pharmacol Ther · July 1, 2004 BACKGROUND: Insulin sensitizing agents may be useful in treatment of non-alcoholic fatty liver disease. AIM: A pilot study to evaluate the efficacy and safety of metformin in non-alcoholic fatty liver disease. METHODS: In an open labelled study, patients w ... Full text Link to item Cite

Fatty liver, hypertension, and the metabolic syndrome.

Journal Article Gut · July 2004 The prevalence of fatty liver in non-obese non-diabetic hypertensive patients is at least twice that of the general population and may be related to increases in insulin resistance and body weight. ... Full text Link to item Cite

Hematopoietic stem cells convert into liver cells within days without fusion.

Journal Article Nat Cell Biol · June 2004 Both plasticity and cell fusion have been suggested to have a role in germ-layer switching. To understand the mechanisms underlying cell fate changes, we have examined a highly enriched population of hematopoietic stem cells (HSCs) in vitro or in vivo in r ... Full text Link to item Cite

Alcoholic liver disease

Journal Article · April 23, 2004 Full text Cite

Hepatic fibrogenesis requires sympathetic neurotransmitters.

Journal Article Gut · March 2004 BACKGROUND AND AIMS: Hepatic stellate cells (HSC) are activated by liver injury to become proliferative fibrogenic myofibroblasts. This process may be regulated by the sympathetic nervous system (SNS) but the mechanisms involved are unclear. METHODS: We st ... Full text Link to item Cite

Oval cells compensate for damage and replicative senescence of mature hepatocytes in mice with fatty liver disease.

Journal Article Hepatology · February 2004 Hepatic steatosis may have a generally benign prognosis, either because most hepatocytes are not significantly injured or mechanisms to replace damaged hepatocytes are induced. To determine the relative importance of these mechanisms, we compared hepatocyt ... Full text Link to item Cite

Innate immunity in the liver.

Journal Article Curr Opin Gastroenterol · November 2003 PURPOSE OF REVIEW: The liver is constantly exposed to large varieties of antigens that are derived from the gastrointestinal tract, including dietary antigens, pathogens, and toxins. Its function as a major immune organ is now being appreciated. The liver ... Full text Link to item Cite

Oxidative stress and oval cell accumulation in mice and humans with alcoholic and nonalcoholic fatty liver disease.

Journal Article Am J Pathol · October 2003 In animals, the combination of oxidative liver damage and inhibited hepatocyte proliferation increases the numbers of hepatic progenitors (oval cells). We studied different murine models of fatty liver disease and patients with nonalcoholic fatty liver dis ... Full text Link to item Cite

Sympathetic nervous system inhibition increases hepatic progenitors and reduces liver injury.

Journal Article Hepatology · September 2003 Recovery from liver damage might be enhanced by encouraging repopulation of the liver by endogenous hepatic progenitor cells. Oval cells are resident hepatic stem cells that promote liver regeneration and repair. Little is known about the mediators that re ... Full text Link to item Cite

Norepinephrine induces hepatic fibrogenesis in leptin deficient ob/ob mice.

Journal Article Biochem Biophys Res Commun · August 22, 2003 Leptin's actions on certain cells require a leptin-inducible neurotransmitter, norepinephrine (NE). NE modulates hepatic fibrosis. Therefore, decreased NE may explain why leptin deficiency inhibits hepatic fibrosis. We manipulated adrenergic activity in le ... Full text Link to item Cite

In vitro interleukin-6 treatment prevents mortality associated with fatty liver transplants in rats.

Journal Article Gastroenterology · July 2003 BACKGROUND & AIMS: Orthotopic liver transplantation is currently the only curative therapy for chronic end-stage liver disease and acute liver failure. However, a scarcity of cadaveric donors has led to a critical shortage of organs available for transplan ... Full text Link to item Cite

Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis.

Journal Article JAMA · June 11, 2003 Cryptogenic cirrhosis is a common cause of liver-related morbidity and mortality in the United States. Nonalcoholic fatty liver disease (NAFLD) is now recognized as the most common cause of cryptogenic cirrhosis. However, the diagnosis of cirrhosis in pati ... Full text Link to item Cite

Elevated hepatocyte levels of the Forkhead box A2 (HNF-3beta) transcription factor cause postnatal steatosis and mitochondrial damage.

Journal Article Hepatology · June 2003 The Forkhead box (Fox) transcription factor Foxa2 (HNF-3beta) and related family members Foxa1 (HNF-3alpha) and Foxa3 (HNF-3gamma) act in concert with other hepatocyte nuclear factors (HNF) to coordinately regulate liver-specific gene expression. To circum ... Full text Link to item Cite

Hyperlactataemia syndromes associated with HIV therapy.

Journal Article Lancet Infect Dis · June 2003 Hyperlactataemia is seen in 8-18.3% of HIV-infected patients taking nucleoside-analogue reverse transcriptase inhibitors (NRTIs). Recent epidemiological studies suggest that most episodes are transient and subclinical. However, symptomatic and occasionally ... Full text Link to item Cite

The prevalence and etiology of elevated aminotransferase levels in the United States.

Journal Article Am J Gastroenterol · May 2003 Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown. We analyzed data on adults ages 17 yr and older (N = ... Full text Link to item Cite

Hepatic allograft-derived Kupffer cells regulate T cell response in rats.

Journal Article Liver Transpl · May 2003 In liver transplantation, the development of tolerance is associated with an increased rate of apoptosis of T lymphocytes in the portal inflammatory infiltrate and the presence of an intragraft Th2-like T cell population. Underlying mechanisms are poorly u ... Full text Link to item Cite

Norepinephrine and neuropeptide Y promote proliferation and collagen gene expression of hepatic myofibroblastic stellate cells.

Journal Article Biochem Biophys Res Commun · March 21, 2003 The mechanisms initiating and perpetuating the fibrogenic response in the injured liver are not well understood. Hepatic stellate cells are activated by liver injury to become proliferative and fibrogenic myofibroblasts. Emerging evidence suggests that the ... Full text Link to item Cite

Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.

Journal Article Hepatology · February 2003 Ob/ob mice, a model for nonalcoholic fatty liver disease (NAFLD), develop intestinal bacterial overgrowth and overexpress tumor necrosis factor alpha (TNF-alpha). In animal models for alcoholic fatty liver disease (AFLD), decontaminating the intestine or i ... Full text Link to item Cite

Hepatic ATP reserve and efficiency of replenishing: comparison between obese and nonobese normal individuals.

Journal Article Am J Gastroenterol · February 2003 OBJECTIVE: Although obesity-associated fatty liver disease is emerging as one of the most common diseases in hepatology practice, it is unclear why liver disease prevalence increases with obesity. Because impaired energy homeostasis enhances the susceptibi ... Full text Link to item Cite

Acetylcholine promotes the proliferation and collagen gene expression of myofibroblastic hepatic stellate cells.

Journal Article Biochem Biophys Res Commun · January 3, 2003 The mechanisms that initiate and perpetuate the fibrogenic response, during liver injury, are unclear. Animal studies, however, strongly support a role for the autonomic nervous system (ANS) in wound healing. Therefore, the ANS may also mediate the develop ... Full text Link to item Cite

The liver in obesity and type 2 diabetes mellitus.

Journal Article Clin Liver Dis · November 2002 Obesity and type 2 diabetes are associated strongly with NAFLD. It is not clear if one of these conditions causes the others, or if all are consequences of another process. Although NAFLD is known to occur in overly lean individuals, which indicates that e ... Full text Link to item Cite

Ethanol induces redox-sensitive cell-cycle inhibitors and inhibits liver regeneration after partial hepatectomy.

Journal Article Alcohol Clin Exp Res · November 2002 BACKGROUND: Doses of ethanol (EtOH) that are not overtly cytotoxic inhibit mitogen-induced hepatocyte proliferation and delay liver regeneration after 70% partial hepatectomy (PH). The mechanisms for this are poorly understood. This study evaluates the hyp ... Full text Link to item Cite

Murine leptin deficiency alters Kupffer cell production of cytokines that regulate the innate immune system.

Journal Article Gastroenterology · October 2002 BACKGROUND & AIMS: ob/ob mice are used to study the mechanisms that regulate the progression from steatosis to nonalcoholic steatohepatitis. The livers of ob/ob mice are depleted of CD4-positive natural killer cells, components of the innate immune system ... Full text Link to item Cite

Animal models of steatohepatitis.

Journal Article Best Pract Res Clin Gastroenterol · October 2002 Animal models of hepatic steatosis and steatohepatitis have improved our understanding of the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Three models, genetically obese ob/ob mice, lipoatrophic mice and normal rats fed choline-deficient, me ... Full text Link to item Cite

STAT-3 overexpression and p21 up-regulation accompany impaired regeneration of fatty livers.

Journal Article Am J Pathol · July 2002 Fatty liver is an important cause of morbidity in humans and is linked to impaired liver regeneration after liver injury, but the mechanisms for impaired liver regeneration remain unknown. In the normal liver, the interleukin (IL)-6/STAT-3 pathway is thoug ... Full text Link to item Cite

Liver regeneration.

Journal Article Front Biosci · July 1, 2002 Unlike other vital organs, the liver typically regenerates after injury. Indeed, the very factors that cause liver injury initiate a reparative process in the residual liver that includes the induction of cytoprotective mechanisms, deletion of mortally wou ... Full text Link to item Cite

Hepatic steatosis and type 2 diabetes mellitus.

Journal Article Curr Diab Rep · June 2002 Type 2 diabetes is strongly associated with nonalcoholic fatty liver disease (NAFLD), a spectrum of liver damage that ranges from relatively benign hepatic steatosis to potentially fatal cirrhosis. The severities of insulin resistance and liver damage para ... Full text Link to item Cite

Nonalcoholic fatty liver disease.

Journal Article Gastroenterology · May 2002 Full text Link to item Cite

Liver disease in alcohol abusers: clinical perspective.

Journal Article Alcohol · May 2002 Alcoholic liver disease remains one of the most common causes of chronic liver disease in the world. The severity of liver damage related to alcohol varies among different individuals and even within any given individual at different times. Certain symptom ... Full text Link to item Cite

Chronic ethanol exposure potentiates lipopolysaccharide liver injury despite inhibiting Jun N-terminal kinase and caspase 3 activation.

Journal Article J Biol Chem · April 12, 2002 Although ethanol is known to sensitize hepatocytes to tumor necrosis factor (TNF) lethality, the mechanisms involved remain controversial. Recently, others have shown that adding TNFalpha to cultures of ethanol-pretreated hepatocytes provokes the mitochond ... Full text Link to item Cite

Fat and the liver--a molecular overview.

Journal Article Semin Gastrointest Dis · January 2002 Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that occurs in nondrinkers but which cannot be distinguished from alcohol-induced liver disease histologically. There are no diagnostic blood tests for NAFLD but the disease is associated ... Link to item Cite

Molecular pathology and clinical aspects of alcohol-induced tissue injury.

Journal Article Alcohol Clin Exp Res · January 2002 Proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada; organized and co-chaired by Patricia E. Molina and Manuela Neuman. The presentations were (1) Mechanisms of alcohol-induced cell injury by Craig McClain; (2) Cytokines in alcoholic ste ... Link to item Cite

Nonalcoholic steatosis and steatohepatitis IV. Nonalcoholic fatty liver disease abnormalities in macrophage function and cytokines.

Journal Article Am J Physiol Gastrointest Liver Physiol · January 2002 Macrophage products, such as cytokines, prostanoids, nitric oxide, and reactive oxygen intermediates, influence the function and viability of macrophages and neighboring cells. Given that the liver has one of the largest resident macrophage populations in ... Full text Link to item Cite

Disrupted signaling and inhibited regeneration in obese mice with fatty livers: implications for nonalcoholic fatty liver disease pathophysiology.

Journal Article Hepatology · October 2001 The impaired regenerative capacity of fatty livers might promote the progression of nonalcoholic fatty liver disease (NAFLD). To identify mechanisms involved, regenerative responses were compared in normal mice and ob/ob mice (a model for NAFLD) after part ... Full text Link to item Cite

Fatty liver vulnerability to endotoxin-induced damage despite NF-kappaB induction and inhibited caspase 3 activation.

Journal Article Am J Physiol Gastrointest Liver Physiol · August 2001 Fatty livers are sensitive to lipopolysaccharide (LPS) damage. This study tests the hypothesis that this vulnerability occurs because protective, antiapoptotic mechanisms are not upregulated appropriately. Genetically obese, leptin-deficient ob/ob mice, a ... Full text Link to item Cite

Hepatic hyperplasia in noncirrhotic fatty livers: is obesity-related hepatic steatosis a premalignant condition?

Journal Article Cancer Res · July 1, 2001 It is not known whether obesity increases the risk for hepatocellular carcinoma (HCC) simply because it promotes cirrhosis, a general risk factor for HCC, or via some other mechanism that operates independently of cirrhosis. If the latter occurs, then hepa ... Link to item Cite

Nonalcoholic fatty liver disease: implications for alcoholic liver disease pathogenesis.

Journal Article Alcohol Clin Exp Res · May 2001 This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The presentation was Nonalcoholic fatty liver disease: Implications for alcoholic liver disease pathogenesis, by Anna Mae Diehl. ... Full text Link to item Cite

Obesity and female gender increase breath ethanol concentration: potential implications for the pathogenesis of nonalcoholic steatohepatitis.

Journal Article Am J Gastroenterol · April 2001 OBJECTIVES: Similarities between histological features of alcoholic hepatitis and obesity-related liver disease suggest a common pathogenic mechanism. Because intestinal bacteria can produce ethanol, it is conceivable that intestinally derived alcohol may ... Full text Link to item Cite

Animal models of steatosis.

Journal Article Semin Liver Dis · 2001 The lipid content of hepatocytes is regulated by the integrated activities of cellular enzymes that catalyze lipid uptake, synthesis, oxidation, and export. When "input" of fats into these systems (either because of increased fatty acid delivery, hepatic f ... Full text Link to item Cite

Increased gastrointestinal ethanol production in obese mice: implications for fatty liver disease pathogenesis.

Journal Article Gastroenterology · November 2000 BACKGROUND & AIMS: Similarities in the hepatic responses to obesity and ethanol exposure suggest that these conditions evoke common pathogenic mechanisms. Thus, it is possible that ethanol exposure is increased in obesity. Given that intestinal bacteria ca ... Full text Link to item Cite

Metformin reverses fatty liver disease in obese, leptin-deficient mice.

Journal Article Nat Med · September 2000 There is no known treatment for fatty liver, a ubiquitous cause of chronic liver disease. However, because it is associated with hyperinsulinemia and insulin-resistance, insulin-sensitizing agents might be beneficial. To evaluate this possibility, insulin- ... Full text Link to item Cite

Mitochondrial adaptations to obesity-related oxidant stress.

Journal Article Arch Biochem Biophys · June 15, 2000 It is not known why viable hepatocytes in fatty livers are vulnerable to necrosis, but associated mitochondrial alterations suggest that reactive oxygen species (ROS) production may be increased. Although the mechanisms for ROS-mediated lethality are not w ... Full text Link to item Cite

Cytokine regulation of liver injury and repair.

Journal Article Immunol Rev · April 2000 By comparing the hepatic responses to tumor necrosis factor (TNF)-alpha that occur during situations that promote liver injury (such as obesity or chronic exposure to ethanol) with those that occur after stimuli (such as partial hepatectomy) that lead to l ... Full text Link to item Cite

Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage.

Journal Article Hepatology · March 2000 Although obesity-related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure. The purpose of this study was to determine if immunologic priming might be involved by determining if fatty livers resemble normal livers ... Full text Link to item Cite

Kupffer cell depletion by CI2MDP-liposomes alters hepatic cytokine expression and delays liver regeneration after partial hepatectomy.

Journal Article Liver · February 2000 BACKGROUND: Although Kupffer cells (KCs) are capable of producing important growth-stimulating cytokines, their role in liver regeneration following partial hepatectomy (PH) remains poorly understood. METHODS: In the present study liver regeneration was st ... Full text Link to item Cite

Chronic ethanol consumption induces the production of tumor necrosis factor-α and related cytokines in liver and adipose tissue

Journal Article Alcoholism: Clinical and Experimental Research · December 1, 1999 Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-α (TNF-α), parallel the evolution of liver injury in rats and humans with alcoholic liver disease. However, the possibility that TNF-α expression may be indu ... Cite

Alterations in liver ATP homeostasis in human nonalcoholic steatohepatitis: a pilot study.

Journal Article JAMA · November 3, 1999 CONTEXT: The mechanisms that drive progression from fatty liver to steatohepatitis and cirrhosis are unknown. In animal models, obese mice with fatty livers are vulnerable to liver adenosine triphosphate (ATP) depletion and necrosis, suggesting that altere ... Full text Link to item Cite

Effect of ethanol on tumor necrosis factor signaling during liver regeneration.

Journal Article Clin Biochem · October 1999 OBJECTIVES: The liver has tremendous regenerative capacity but can be damaged by toxins, such as ethanol (EtOH). It has long been known that EtOH inhibits liver regeneration. Recent work demonstrates that the proinflammatory cytokine, tumor necrosis factor ... Full text Link to item Cite

Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control "the benefits of losing control".

Journal Article J Bioenerg Biomembr · October 1999 Uncoupling proteins, a subgroup of the mitochondrial anion transporter superfamily, have been identified in prokaryotes, plants, and mammalian cells. Evolutionary conservation of these molecules reflects their importance as regulators of two critical mitoc ... Full text Link to item Cite

Cytokines and the molecular mechanisms of alcoholic liver disease.

Journal Article Alcohol Clin Exp Res · September 1999 This manuscript was given as a plenary lecture at the annual meeting of the Research Society on Alcoholism in July of 1999. It describes the general mechanisms by which tumor necrosis factor (TNF) alpha, an injury-related cytokine, promotes liver regenerat ... Link to item Cite

Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes.

Journal Article Gastroenterology · May 1999 BACKGROUND & AIMS: Hepatic steatosis reflects the accumulation of triglycerides and free fatty acids in hepatocytes. Although lipids and their metabolites are potentially hepatotoxic, the absence of overt injury in fatty livers suggests that adaptive respo ... Full text Link to item Cite

Mitochondrial proteins that regulate apoptosis and necrosis are induced in mouse fatty liver.

Journal Article Hepatology · April 1999 Fatty liver is common in nonalcoholic, obese individuals and in lean people who consume alcohol chronically. Although fatty liver is typically benign, a subset of individuals with steatosis develop steatohepatitis and eventually cirrhosis. The disparate ou ... Full text Link to item Cite

Tumor necrosis factor increases mitochondrial oxidant production and induces expression of uncoupling protein-2 in the regenerating mice [correction of rat] liver.

Journal Article Hepatology · March 1999 The growth-stimulatory actions of tumor necrosis factor alpha (TNF-alpha) after partial hepatectomy (PH) are difficult to reconcile with its well-established role in the genesis of liver injury. The lethal actions of TNF are thought to involve the inductio ... Full text Link to item Cite

Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion.

Journal Article J Biol Chem · February 26, 1999 Uncoupling protein 2 (UCP2) uncouples respiration from oxidative phosphorylation and may contribute to obesity through effects on energy metabolism. Because basal metabolic rate is decreased in obesity, UCP2 expression is predicted to be reduced. Paradoxic ... Full text Link to item Cite

Phenotypic abnormalities in macrophages from leptin-deficient, obese mice.

Journal Article Am J Physiol · February 1999 Obesity is a complex syndrome that involves defective signaling by a number of different factors that regulate appetite and energy homeostasis. Treatment with exogenous leptin reverses hyperphagia and obesity in ob/ob mice, which have a mutation that cause ... Full text Link to item Cite

Nonalcoholic steatohepatitis.

Journal Article Semin Liver Dis · 1999 Nonalcoholic steatohepatitis (NASH) is an hepatic disorder with histologic features of alcohol-induced liver disease that occurs in individuals who do not consume significant alcohol. NASH is believed to be one of the most common explanations for abnormal ... Full text Link to item Cite

Roles of CCAAT/enhancer-binding proteins in regulation of liver regenerative growth.

Journal Article J Biol Chem · November 20, 1998 The expressions and activities of several CCAAT/enhancer-binding proteins (C/EBP) isoforms fluctuate in the regenerating liver. The physiological implications of these variations in C/EBP function remain poorly characterized in the setting of regeneration. ... Full text Link to item Cite

Impaired liver regeneration in inducible nitric oxide synthasedeficient mice.

Journal Article Proc Natl Acad Sci U S A · November 10, 1998 The mechanisms that permit adult tissues to regenerate when injured are not well understood. Initiation of liver regeneration requires the injury-related cytokines, tumor necrosis factor (TNF) alpha and interleukin (IL) 6, and involves the activation of cy ... Full text Link to item Cite

Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism.

Journal Article Biochem Biophys Res Commun · October 9, 1998 The liver is a target for bacterial lipopolysaccharide (LPS) and participates in the metabolic response to endotoxemia. Recently published evidence indicates that LPS increases the expression of mitochondrial uncoupling protein-2 (UCP-2) mRNAs in several t ... Full text Link to item Cite

Effects of chronic ethanol consumption on cytokine regulation of liver regeneration.

Journal Article Am J Physiol · October 1998 Ethanol ingestion may interrupt the proregenerative signal transduction that is initiated by injury-related cytokines such as tumor necrosis factor (TNF)-alpha and TNF-alpha- inducible cytokines including interleukin (IL)-6. To test this theory, liver rege ... Full text Link to item Cite

Chronic ethanol consumption induces the production of tumor necrosis factor-alpha and related cytokines in liver and adipose tissue.

Journal Article Alcohol Clin Exp Res · August 1998 Increases in monocyte/macrophage production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), parallel the evolution of liver injury in rats and humans with alcoholic liver disease. However, the possibility that TNF-alpha expression ... Full text Link to item Cite

Tumor necrosis factor-alpha stimulates the maturation of sterol regulatory element binding protein-1 in human hepatocytes through the action of neutral sphingomyelinase.

Journal Article J Biol Chem · February 27, 1998 The mechanism by which genes involved in cholesterol biosynthesis and import are preferentially up-regulated in response to sterol depletion was elucidated with the cloning of sterol regulatory element binding protein-1 (SREBP-1). SREBP-1 is a transcriptio ... Full text Link to item Cite

Alcoholic liver disease.

Journal Article Clin Liver Dis · February 1998 Alcohol has been implicated in the genesis of liver disease for centuries. Significant progress has been made in our understanding of the pathogenesis of ALD. It is now apparent that both the consumption and the metabolism of alcohol promote the production ... Full text Link to item Cite

Leptin regulates proinflammatory immune responses.

Journal Article FASEB J · January 1998 Obesity is associated with an increased incidence of infection, diabetes, and cardiovascular disease, which together account for most obesity-related morbidity and mortality. Decreased expression of leptin or of functional leptin receptors results in hyper ... Link to item Cite

Altered cyclic AMP-dependent human chorionic gonadotropin production in cultured human placental trophoblasts exposed to ethanol.

Journal Article Biochem Pharmacol · January 1, 1998 Chronic ethanol abuse during pregnancy can cause fetal injury, including the fetal alcohol syndrome (FAS). A contributing factor in this fetal injury may be the effect of ethanol on placental function. Previous studies have shown that ethanol treatment inc ... Full text Link to item Cite

Bile ducts and portal and central veins are major producers of tumor necrosis factor alpha in regenerating rat liver.

Journal Article Gastroenterology · June 1997 BACKGROUND & AIMS: Tumor necrosis factor (TNF) alpha mediates both liver injury and regeneration. Kupffer cells are thought to produce TNF because gadolinium chloride (GdCl), a drug that depletes Kupffer cells, prevents TNF-mediated injury. However, GdCl i ... Full text Link to item Cite

Alcoholic liver disease: natural history.

Journal Article Liver Transpl Surg · May 1997 Alcohol has been implicated in the genesis of liver disease for centuries. Modern epidemiological data from many societies corroborate the correlation between per capita consumption of alcohol and deaths from cirrhosis. Although significant progress has be ... Link to item Cite

Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver.

Journal Article Hepatology · April 1997 Tumor necrosis factor alpha (TNF), initiates a cytokine cascade that promotes hepatocyte proliferation after 70% partial hepatectomy (PH) but the mechanisms regulating TNF production after PH are unknown. We previously reported that gadolinium chloride (Gd ... Full text Link to item Cite

Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis.

Journal Article Proc Natl Acad Sci U S A · March 18, 1997 Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive t ... Full text Link to item Cite

The role of cytokines in hepatic regeneration

Journal Article Current Opinion in Gastroenterology · January 1, 1997 Regulation of the regenerative response to liver injury is a complex process. Recent work from several groups demonstrates that cytokines, including tumor necrosis factor-α and tumor necrosis factor-regulated cytokines, such as interleukin-6, play a critic ... Full text Cite

Liver transplantation for alcoholic liver disease.

Journal Article Clin Transplant · December 1996 UNLABELLED: Orthotopic liver transplantation (OLT) for individuals with alcoholic liver disease (ALD) remains controversial. This review was designed to evaluate the survival, recidivism, and rehabilitation of the alcoholic liver transplant recipient in a ... Link to item Cite

Alcohol and cytokine-inducible transcription factors.

Journal Article Alcohol Clin Exp Res · December 1996 Cytokines, such as TNF alpha, modulate the behavior of many cells by regulating the expression of a wide array of genes. When a cytokine binds to its receptor on the cell surface, the receptor becomes activated and activates signal transduction cascades. T ... Full text Link to item Cite

Differential regulation of hepatocyte DNA synthesis by cAMP in vitro in vivo.

Journal Article Am J Physiol · November 1996 Adenosine 3',5'-cyclic monophosphate (cAMP) prevents epidermal growth factor (EGF)-induced DNA synthesis in many types of cultured cells, including hepatocytes, but its effects on cellular proliferation in vivo are unknown. This study compares the effects ... Full text Link to item Cite

Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines.

Journal Article Shock · October 1996 Gadolinium chloride (GdCl3) is commonly used to deplete the liver of Kupffer cells (KC) and has been shown to decrease hepatic phagocytic activity and to abolish hepatic expression of certain KC-specific antigens. However, the exact fate of the KCs after G ... Full text Link to item Cite

Tumor necrosis factor alpha promotes nuclear localization of cytokine-inducible CCAAT/enhancer binding protein isoforms in hepatocytes.

Journal Article J Biol Chem · July 26, 1996 Hepatocytes were cultured in the presence of recombinant tumor necrosis factor (TNF) alpha or mutated TNF alpha peptides that specifically activate either p55 or p75 TNF receptors to determine if TNF alpha can activate cytokine-inducible CCAAT/enhancer bin ... Full text Link to item Cite

Ethanol exposure alters the phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element binding activity in rat cerebellum.

Journal Article J Pharmacol Exp Ther · July 1996 The purpose of the present study was to track the acute effects of ethanol on the cerebellar adenylyl cyclase cascade from membrane to nucleus and to determine how this important signaling pathway neuroadapts during chronic ethanol exposure. An acute ethan ... Link to item Cite

Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats.

Journal Article Am J Physiol · June 1996 Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl ... Full text Link to item Cite

Adenovirus-mediated transfer of CCAAT/enhancer-binding protein-alpha identifies a dominant antiproliferative role for this isoform in hepatocytes.

Journal Article J Biol Chem · March 29, 1996 CCAAT/enhancer-binding protein (C/EBP) isoforms are thought to be important regulators of the hepatocyte phenotype. However, the specific physiological roles of different isoforms are poorly understood because hepatocytes express multiple C/EBPs, and vario ... Full text Link to item Cite

Liver regeneration 3: Regulation of signal transduction during liver regeneration.

Journal Article FASEB J · February 1996 The liver has a tremendous capacity to regenerate. For example, after extensive hepatic resection, remaining hepatocytes proliferate to restore the mass of the organ within days to weeks. This proliferative response is fascinating because hepatocytes rarel ... Full text Link to item Cite

REVIEW: Regulation of liver regeneration by pro-inflammatory cytokines

Journal Article Journal of Gastroenterology and Hepatology (Australia) · January 1, 1996 The liver has tremendous regenerative capacity. This distinguishes it from other vital organs (e.g. the brain, heart and lungs) that cannot replace functional tissue once it has been destroyed. Although hepatocytes rarely proliferate in the healthy adult l ... Full text Cite

Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding.

Journal Article Hepatology · November 1995 Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been ... Link to item Cite

Tumor necrosis factor-alpha modulates CCAAT/enhancer binding proteins-DNA binding activities and promotes hepatocyte-specific gene expression during liver regeneration.

Journal Article Hepatology · July 1995 Injury-related cytokines, such as tumor necrosis factor-alpha (TNF), may preserve liver-specific gene expression during the subsequent regenerative response by modulating the activity of transcription factors, including CCAAT/enhancer binding proteins (C/E ... Full text Link to item Cite

Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding

Journal Article Hepatology · 1995 Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-κB) activity, and NF-κB activity has been shown to ... Cite

Intrahepatic, extramedullary hematopoiesis mimicking hemangioma on technetium-99m red blood cell SPECT examination.

Journal Article Clin Imaging · 1995 Cavernous hemangiomas are the most common lesion of the liver. Because of the risk of hemorrhage inherent in percutaneous biopsy of such lesions, noninterventional modalities (such as CT, ultrasound, MRI and Technetium-99m red blood cell imaging) have been ... Full text Link to item Cite

Tumor necrosis factor-alpha induces c-jun during the regenerative response to liver injury.

Journal Article Am J Physiol · October 1994 After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with a ... Full text Link to item Cite

Altered levels of prothymosin immunoreactive peptide, a growth-related gene product, during liver regeneration after chronic ethanol feeding.

Journal Article Alcohol Clin Exp Res · June 1994 Liver regeneration is regulated by the orderly activation of growth-related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol-associated differences in the hepatic mRNA levels of several ... Full text Link to item Cite

Selective induction of CCAAT/enhancer binding protein isoforms occurs during rat liver development.

Journal Article Gastroenterology · June 1994 BACKGROUND/AIMS: Recent evidence suggests that CCAAT/enhancer binding protein (C/EBP) transcription factors may regulate hepatocyte terminal differentiation. METHODS: To explore this possibility, the present study looked for variations in the expression or ... Full text Link to item Cite

Regenerative changes in C/EBP alpha and C/EBP beta expression modulate binding to the C/EBP site in the c-fos promoter.

Journal Article Hepatology · February 1994 CCAAT/enhancer binding proteins are a family of basic zipper DNA binding proteins that regulate transcription of several liver-specific genes and certain growth-related genes. Growth-related variations in the nuclear expression of one or more of the CCAAT/ ... Link to item Cite

A 30-kDa alternative translation product of the CCAAT/enhancer binding protein alpha message: transcriptional activator lacking antimitotic activity.

Journal Article Proc Natl Acad Sci U S A · October 15, 1993 Full-length (42 kDa) CCAAT/enhancer binding protein alpha (C/EBP alpha) (p42) has been implicated in the transcriptional activation of adipocyte genes including the 422(aP2) and C/EBP alpha genes during differentiation of 3T3-L1 preadipocytes. We have iden ... Full text Link to item Cite

Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-alpha.

Journal Article Hepatology · June 1993 The pathogenesis of chronic alcoholic liver disease is uncertain, but it may reflect an impaired wound healing response to ethanol-induced liver injury. Cell-to-cell communication such as that mediated by the cytokine tumor necrosis factor is necessary for ... Link to item Cite

Cytokines and alcoholic liver disease.

Journal Article Semin Liver Dis · May 1993 It is clear that cytokines cause metabolic disturbances that are similar to known complications of AH. TNF appears to be a proximal mediator of multiple types of experimental liver injury and TNF activity is elevated in ALD, as are the levels of certain ot ... Full text Link to item Cite

Gallstones and Laparoscopic Cholecystectomy

Journal Article JAMA: The Journal of the American Medical Association · February 24, 1993 Full text Cite

Chronic ethanol treatment increases expression of inhibitory G-proteins and reduces adenylylcyclase activity in the central nervous system of two lines of ethanol-sensitive mice.

Journal Article J Biol Chem · February 5, 1993 The possibility that a 7-day period of ethanol exposure could regulate expression of specific GTP-binding regulatory proteins was investigated in two distinct brain regions from two different lines of ethanol-sensitive mice. Following ethanol treatment, pl ... Link to item Cite

Chronic ethanol consumption disturbs G-protein expression and inhibits cyclic AMP-dependent signaling in regenerating rat liver.

Journal Article Hepatology · November 1992 Evidence suggests that ethanol desensitizes hepatocytes to the trophic effects of hormones. Cyclic AMP-dependent signals are important regulators of intermediary metabolism, cellular proliferation and differentiation, and modulate liver growth during hepat ... Link to item Cite

Antibodies to tumor necrosis factor-alpha inhibit liver regeneration after partial hepatectomy.

Journal Article Am J Physiol · October 1992 Certain cytokines that are produced in liver may act as growth factors to facilitate wound healing and, hence, may influence liver regeneration. However, this hypothesis has not been directly tested. To determine whether the cytokine response evoked by par ... Full text Link to item Cite

Differential expression of guanine nucleotide-binding proteins enhances cAMP synthesis in regenerating rat liver.

Journal Article J Clin Invest · June 1992 Events leading to cAMP accumulation after partial hepatectomy (PH) and effects of cAMP on hormonal induction of DNA synthesis in hepatocytes were characterized. Hepatic cAMP peaked biphasically post-PH and paralleled changes in adenylyl cyclase activity. F ... Full text Link to item Cite

Alcohol-related trafficking accidents.

Journal Article Hepatology · May 1992 Full text Link to item Cite

Ethanol-associated alterations in the kinetics of putrescine uptake and metabolism by the regenerating liver.

Journal Article Alcohol Clin Exp Res · February 1992 Biosynthesis of the polyamines, putrescine, spermidine, and spermine is required for DNA synthesis and liver regeneration after partial hepatectomy. We have previously reported that chronic ethanol consumption impairs polyamine synthesis and significantly ... Full text Link to item Cite

Antibodies to hepatitis B virus and hepatitis C virus in alcoholic hepatitis and cirrhosis: their prevalence and clinical relevance. The VA Cooperative Study Group (No. 119).

Journal Article Hepatology · October 1991 Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis ... Full text Link to item Cite

Ethanol interferes with regeneration-associated changes in biotransforming enzymes: a potential mechanism underlying ethanol's carcinogenicity?

Journal Article Hepatology · April 1991 The effects of chronic ethanol consumption on enzyme systems involved in carcinogen activation and detoxification were studied in a rat model of liver regeneration. In control rats, steady-state messenger RNAs of cytochrome P450j decreased 12 to 24 hr afte ... Link to item Cite

Antibodies to hepatitis B virus and hepatitis C virus in alcoholic hepatitis and cirrhosis: Their prevalence and clinical relevance

Journal Article Hepatology · January 1, 1991 Patients with overt alcoholic liver disease who had participated in a multicenter therapeutic trial and subgroups of controls (i.e., alcoholic patients without liver disease and patients with neither alcoholism nor liver disease) were tested for hepatitis ... Full text Cite

Ethanol inhibits liver regeneration in rats without reducing transcripts of key protooncogenes.

Journal Article Gastroenterology · October 1990 The mechanisms responsible for ethanol-associated inhibition of liver regeneration are poorly understood but may involve the modulation of protooncogene expression. To test this hypothesis, the steady-state messenger RNA levels of several protooncogenes in ... Full text Link to item Cite

Supplemental putrescine reverses ethanol-associated inhibition of liver regeneration.

Journal Article Hepatology · October 1990 Biosynthesis of the polyamines, putrescine, spermidine and spermine, is required for DNA synthesis and liver regeneration after partial hepatectomy. Chronic ethanol consumption impairs polyamine synthesis during the prereplicative phase after partial hepat ... Full text Link to item Cite

Effect of ethanol on polyamine synthesis during liver regeneration in rats.

Journal Article J Clin Invest · February 1990 Ethanol consumption retards the hepatic regenerative response to injury. This may contribute to the pathogenesis of liver injury in alcoholic individuals. The mechanisms responsible for ethanol-associated inhibition of liver regeneration are poorly underst ... Full text Link to item Cite

Liver enzymes and liver biopsy (I: Reply)

Journal Article Annals of Internal Medicine · January 1, 1990 Cite

Treatment of chronic hepatitis B

Journal Article Practical Gastroenterology · December 1, 1989 Chronic hepatitis B is a problem of great magnitude worldwide. In China, Southeast Asia, and sub-Saharan Africa, where the bulk of carriers reside, the disease is transmitted predominantly perinatally by a carrier mother. Infected newborn babies almost inv ... Cite

Is liver biopsy useful in the evaluation of patients with chronically elevated liver enzymes?

Journal Article Ann Intern Med · September 15, 1989 STUDY OBJECTIVE: To determine the diagnostic usefulness of percutaneous liver biopsy in evaluating patients with chronically elevated liver-associated enzymes. DESIGN: Comparison of diagnosis made before biopsy by one physician on the basis of a noninvasiv ... Full text Link to item Cite

Alcoholic liver disease.

Journal Article Med Clin North Am · July 1989 Liver injury may develop in some people who consume alcohol. The pathogenesis of liver damage in such subjects remains obscure. Major histopathologic features of alcohol-associated liver injury include steatosis, steatonecrosis, and cirrhosis. The clinical ... Full text Link to item Cite

Methylprednisolone therapy in patients with severe alcoholic hepatitis. A randomized multicenter trial.

Journal Article Ann Intern Med · May 1, 1989 STUDY OBJECTIVE: To determine the efficacy of a corticosteroid in reducing the short-term mortality of patients with severe alcoholic hepatitis. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. SETTING: Four university teaching hospi ... Full text Link to item Cite

Alcohollike liver disease in nonalcoholics. A clinical and histologic comparison with alcohol-induced liver injury.

Journal Article Gastroenterology · October 1988 Individuals who deny alcohol consumption may develop liver injury that histologically resembles the liver injury found in alcoholic patients. To determine whether any clinical or histologic features distinguish alcoholic and nonalcoholic subjects with "alc ... Link to item Cite

Alcohol and dietary intake in the development of chronic pancreatitis and liver disease in alcoholism.

Journal Article Am J Clin Nutr · July 1988 Alcohol and dietary intake were determined in alcoholic patients with chronic pancreatitis and alcoholic liver disease. Patients with chronic pancreatitis, alcoholic hepatitis, and cirrhosis ingested approximately 50% of their calories as alcohol, and all ... Full text Link to item Cite

The effect of chronic ethanol feeding on ornithine decarboxylase activity and liver regeneration.

Journal Article Hepatology · 1988 The effects of ethanol on liver regeneration are poorly understood. Acute and chronic exposure to ethanol have been found to exert opposite effects on the induction of ornithine decarboxylase, the rate-limiting enzyme for polyamine biosynthesis. Polyamines ... Full text Link to item Cite

A study of patient acceptance of double-contrast barium enema and colonoscopy. Which procedure is preferred by patients?

Journal Article Arch Intern Med · December 1987 To our knowledge, no previous study has addressed the question of which method of evaluation of the lower gastrointestinal tract is preferred by patients, air-contrast barium enema or colonoscopy. Over a four-month period, we asked 189 consecutive patients ... Full text Link to item Cite

Serum angiotensin converting enzyme activity in evaluation of patients with liver disease.

Journal Article Am J Med · August 1987 This study was undertaken to evaluate angiotensin converting enzyme activity in patients with liver disease, and to explore its relationship to thyroid function in patients with liver disease. Serum angiotensin converting enzyme activity and thyroid hormon ... Full text Link to item Cite

Pyridoxine deficiency and ethanol-induced liver injury.

Journal Article Alcohol Clin Exp Res · August 1987 It has been suggested that pyridoxine deficiency may potentiate ethanol-induced liver injury. Our purpose was to clarify the effect of pyridoxine deficiency on ethanol-associated liver injury by comparing liver histology, serum liver enzymes, and the viabi ... Full text Link to item Cite

Changes in plasma amino acids during sobriety in alcoholic patients with and without liver disease.

Journal Article Am J Clin Nutr · October 1986 Plasma amino acid profiles of alcoholic subjects without clinically apparent liver disease, alcoholic patients with biopsy-proven alcoholic hepatitis, and nonalcoholic controls were compared. Differences in the plasma aminograms of alcoholic subjects with ... Full text Link to item Cite

Depression of alcohol dehydrogenase activity in rat hepatocyte culture by dihydrotestosterone.

Journal Article Biochem Pharmacol · January 15, 1986 Hepatocytes harvested from castrated rats retained a higher alcohol dehydrogenase (EC 1.1.1.1) activity than hepatocytes harvested from normal rats during 7 days of culture. Dihydrotestosterone (1 microM) decreased the enzyme activity, after 2 and 5 days o ... Full text Link to item Cite

Crohn's disease and systemic lupus erythematosus.

Journal Article Am J Gastroenterol · November 1985 A 28-year-old man with inflammatory bowel disease with complex extraintestinal involvement was found to have diagnostic features of both systemic lupus erythematosus and Crohn's disease. Although some of the systemic complications of these diseases may ove ... Link to item Cite

Effect of parenteral amino acid supplementation in alcoholic hepatitis.

Journal Article Hepatology · 1985 A controlled randomized study was performed in 15 patients with biopsy-proven alcoholic hepatitis to determine the effect of the administration of a parenteral amino acid-glucose solution for 1 month on nutritional, clinical, biochemical and histological p ... Full text Link to item Cite

Cholestatic hepatitis from erythromycin ethylsuccinate. Report of two cases.

Journal Article Am J Med · May 1984 Cholestatic hepatitis developed in two patients while they were receiving erythromycin ethylsuccinate. Both patients had received the drug without apparent problem within two months of the episode of drug-related cholestatic injury. In both, there was comp ... Full text Link to item Cite

Relationship between pyridoxal 5'-phosphate deficiency and aminotransferase levels in alcoholic hepatitis.

Journal Article Gastroenterology · April 1984 The relationship between pyridoxal phosphate deficiency and activities of serum and liver aminotransferases was studied in 12 patients with alcoholic hepatitis. Plasma pyridoxal phosphate and the activities of liver aminotransferases were initially decreas ... Link to item Cite

Septic arthritis caused by Propionibacterium acnes.

Journal Article JAMA · October 8, 1982 The traditional view that Propionibacterium acnes is nonpathogenic for man, except as an agent associated with acne vulgaris, has been refuted. Propionibacterium acnes has been shown to cause endocarditis, meningitis, and other serious infections. We repor ... Link to item Cite