Scholars@Duke
Cynthia Dianne Guy

Cynthia Dianne Guy

Professor of Pathology
Pathology
cynthia.guy@duke.edu
Duke Box 3712, Durham, NC 27710
206 A Davison Bldg, Durham, NC

Selected Publications

Identification of Potential Therapeutic Targets Against Anthrax-Toxin-Induced Liver and Heart Damage.

Journal Article Toxins (Basel) · January 24, 2025 Anthrax represents a disease resulting from infection by toxin-secreting bacteria, Bacillus anthracis. This research aimed to identify new therapeutic targets to combat anthrax. We performed assays to assess cell viability, apoptosis, glycogen consumption, ... Full text Link to item Cite

MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls.

Journal Article Aliment Pharmacol Ther · November 2024 BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis sta ... 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

A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis.

Journal Article N Engl J Med · February 8, 2024 BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive liver disease with no approved treatment. Resmetirom is an oral, liver-directed, thyroid hormone receptor beta-selective agonist in development for the treatment of NASH with liver fibrosis. ... Full text Link to item Cite

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

Journal Article Ann Hepatol · 2024 The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favor of a change in ... Full text Link to item Cite

A multisociety Delphi consensus statement on new fatty liver disease nomenclature.

Journal Article J Hepatol · December 2023 The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in ... Full text Link to item 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

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 & AIMS: There 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 progressio ... Full text Link to item 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

MRI Quantification of Placebo Effect in Nonalcoholic Steatohepatitis Clinical Trials.

Journal Article Radiology · March 2023 Background Several early-phase clinical trials for the treatment of nonalcoholic steatohepatitis (NASH) use liver fat content as measured with the MRI-derived proton density fat fraction (PDFF) for a primary outcome. These trials have shown relative reduct ... Full text Open Access Link to item Cite

The nonalcoholic steatohepatitis extended hepatocyte ballooning score: histologic classification and clinical significance.

Journal Article Hepatol Commun · February 1, 2023 BACKGROUND AND AIMS: The NAFLD activity score was developed to measure histologic changes in NAFLD during therapeutic trials. Hepatocyte ballooning (HB) is the most specific feature in steatohepatitis diagnosis, yet the impact of variations in HB has not b ... 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

Aldafermin in patients with non-alcoholic steatohepatitis (ALPINE 2/3): a randomised, double-blind, placebo-controlled, phase 2b trial.

Journal Article Lancet Gastroenterol Hepatol · July 2022 BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation, and injury, and is associated with an increased risk of liver transplantation and death. NASH affects more than 16 million people in the USA, and there is ... Full text Link to item Cite

Complexity of ballooned hepatocyte feature recognition: Defining a training atlas for artificial intelligence-based imaging in NAFLD.

Journal Article J Hepatol · May 2022 BACKGROUND & AIMS: Histologically assessed hepatocyte ballooning is a key feature discriminating non-alcoholic steatohepatitis (NASH) from steatosis (NAFL). Reliable identification underpins patient inclusion in clinical trials and serves as a key regulato ... Full text Link to item Cite

Perceptions of Exercise and Its Challenges in Patients With Nonalcoholic Fatty Liver Disease: A Survey-Based Study.

Journal Article Hepatol Commun · February 2022 Exercise is a foundational treatment for nonalcoholic fatty liver disease (NAFLD); however, the majority of patients are unable to initiate and maintain effective exercise habits and remain at increased risk for progressive liver disease. Barriers and limi ... Full text Link to item Cite

Primary hepatic neoplasms arising in cirrhotic livers can have a variable spectrum of neuroendocrine differentiation.

Journal Article Hum Pathol · October 2021 Primary hepatic neoplasms with neuroendocrine differentiation are extremely rare. Their clinicopathological features and molecular genetic basis are largely unknown. We identified four cases of primary hepatic neoplasms with neuroendocrine differentiation. ... 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

Point-of-Care Assessment of DCD Livers During Normothermic Machine Perfusion in a Nonhuman Primate Model.

Journal Article Hepatol Commun · September 2021 Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investig ... 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

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

Reduced MFAP5 expression in stroma of gallbladder adenocarcinoma and its potential diagnostic utility.

Journal Article Virchows Arch · March 2021 The diagnosis of invasive adenocarcinoma of the gallbladder can sometimes be challenging. The presence of true desmoplastic reaction facilitates the diagnosis of invasion. However, desmoplasia-like changes can be observed in benign gallbladder conditions, ... 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

"Bull's eye" appearance of hepatocellular adenomas in patients with glycogen storage disease type I - atypical magnetic resonance imaging findings: Two case reports.

Journal Article World J Clin Cases · February 6, 2021 BACKGROUND: Hepatocellular adenomas are rare tumors that can occur in patients with glycogen storage disease type I. CASE SUMMARY: We herein report two cases of histologically proven hepatocellular adenomas in patients with glycogen storage disease type I. ... Full text Link to item Cite

Efficacy and Safety of Aldafermin, an Engineered FGF19 Analog, in a Randomized, Double-Blind, Placebo-Controlled Trial of Patients With Nonalcoholic Steatohepatitis.

Journal Article Gastroenterology · January 2021 BACKGROUND & AIMS: Aldafermin, an engineered analog of fibroblast growth factor 19, inhibits bile acid synthesis and regulates metabolic homeostasis. We report results from a 24-week, phase 2 study, with serial liver biopsies, of patients with nonalcoholic ... 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

Regenerative hepatic pseudotumor: a new pseudotumor of the liver.

Journal Article Hum Pathol · May 2020 Cases of new pseudotumors of the liver were collected from multiple medical centers. Four resection and 4 biopsy specimens were collected, including 4 women and 4 men at an average age of 48 ± 15 years (range: 28-73 years). The lesions were visible on imag ... Full text Link to item Cite

NGM282 Improves Liver Fibrosis and Histology in 12 Weeks in Patients With Nonalcoholic Steatohepatitis.

Journal Article Hepatology · April 2020 NGM282, an engineered fibroblast growth factor 19 analogue, rapidly and significantly reduced liver fat content in a multicenter, randomized, double-blind, placebo-controlled study in patients with biopsy-confirmed nonalcoholic steatohepatitis (NASH). Howe ... Full text 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

Impact of obeticholic acid on the lipoprotein profile in patients with non-alcoholic steatohepatitis.

Journal Article J Hepatol · January 2020 BACKGROUND & AIMS: Obeticholic acid (OCA), a farnesoid X receptor agonist, increases total and low-density lipoprotein cholesterol (LDL-C) in patients with non-alcoholic steatohepatitis. In the present study, we aimed to evaluate the impact of OCA therapy ... 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

Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

Journal Article Lancet · November 30, 2019 BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterised by hepatic steatosis, inflammation, hepatocellular injury, and progressive liver fibrosis. Resmetirom (MGL-3196) is a liver-directed, orally active, selective thyroid hormone receptor-β agon ... 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

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

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

SENP3-mediated host defense response contains HBV replication and restores protein synthesis.

Journal Article PLoS One · 2019 Certain organs are capable of containing the replication of various types of viruses. In the liver, infection of Hepatitis B virus (HBV), the etiological factor of Hepatitis B and hepatocellular carcinoma (HCC), often remains asymptomatic and leads to a ch ... 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

Serum Interleukin-8, Osteopontin, and Monocyte Chemoattractant Protein 1 Are Associated With Hepatic Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

Journal Article Hepatol Commun · November 2018 The severity of hepatic fibrosis is the primary predictor of liver-related morbidity and mortality in patients with nonalcoholic fatty liver disease (NAFLD). Unfortunately, noninvasive serum biomarkers for NAFLD-associated fibrosis are limited. We analyzed ... Full text Link to item Cite

Reply.

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

Whole-Exome Sequencing Study of Extreme Phenotypes of NAFLD.

Journal Article Hepatol Commun · September 2018 Nonalcoholic fatty liver disease (NAFLD) is a heterogeneous disease with highly variable outcomes. Patients with simple steatosis typically experience a benign course, whereas those with more advanced liver injury, nonalcoholic steatohepatitis (NASH), and ... 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

Nonalcoholic Steatohepatitis: Histopathology Basics Within a Broader Context.

Journal Article Surg Pathol Clin · June 2018 Nonalcoholic fatty liver disease (NAFLD) is a major health concern and the prevalence continues to increase in many industrialized and developing countries around the world. NAFLD affects adults and children. NAFLD-related cirrhosis is expected to become t ... Full text Link to item Cite

Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis.

Journal Article Aliment Pharmacol Ther · March 2018 BACKGROUND: In a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight. AIMS: Because weight lo ... Full text Link to item Cite

Overexpression of SOX11 and TFE3 in Solid-Pseudopapillary Neoplasms of the Pancreas.

Journal Article Am J Clin Pathol · December 20, 2017 OBJECTIVES: To characterize the expression of SOX11 and TFE3 proteins in solid-pseudopapillary neoplasms (SPNs) and their histologic mimickers. METHODS: Immunohistochemistry for SOX11, TFE3, and β-catenin was performed on 31 cases of surgically resected SP ... 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

Reply to Kim et al.

Journal Article Am J Gastroenterol · May 2017 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

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

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

Mixed Adenoneuroendocrine Carcinoma, Amphicrine Type, of the Small Bowel.

Journal Article Am J Clin Pathol · May 2016 OBJECTIVES: Amphicrine-type mixed adenoneuroendocrine carcinomas are exceedingly rare lesions of the gastrointestinal tract, comprising tumor cells simultaneously demonstrating both neuroendocrine and exocrine features. To date, only 14 cases of amphicrine ... 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

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

Hedgehog Signaling is Associated with Liver Response to Fractionated Irradiation in Mice.

Journal Article Cell Physiol Biochem · 2016 BACKGROUND/AIMS: Radiation-induced liver disease (RILD) is a major obstacle in treating liver cancer; however, the mechanisms underlying RILD development remain unclear. Hedgehog (Hh) orchestrates liver response to injury. Herein, we investigated the liver ... Full text Link to item Cite

Giant esophageal lipoma: endoscopic resection.

Journal Article Gastrointest Endosc · October 2015 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

Reply: To PMID 24849310.

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

Reply: To PMID 24123276.

Journal Article Hepatology · March 2015 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

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

Derivation and analysis of viscoelastic properties in human liver: impact of frequency on fibrosis and steatosis staging.

Journal Article IEEE Trans Ultrason Ferroelectr Freq Control · January 2015 Commercially-available shear wave imaging systems measure group shear wave speed (SWS) and often report stiffness parameters applying purely elastic material models. Soft tissues, however, are viscoelastic, and higher-order material models are necessary to ... 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

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

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

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

Retroperitoneal cystic lymphangioma diagnosed by endoscopic ultrasound-guided fine needle aspiration.

Journal Article Clin Endosc · September 2013 Retroperitoneal cystic lymphangiomas are rare tumors of the lymphatic system. These tumors usually present in childhood and are often diagnosed incidentally with imaging procedures. Although benign, they can grow to large sizes and become symptomatic due t ... 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

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

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

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

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

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

Resected pancreatic neuroendocrine tumors: patterns of failure and disease-related outcomes with or without radiotherapy.

Journal Article Int J Radiat Oncol Biol Phys · July 15, 2012 PURPOSE: Pancreatic neuroendocrine tumors (NET) are rare and have better disease-related outcomes compared with pancreatic adenocarcinoma. Surgical resection remains the standard of care, although many patients present with locally advanced or metastatic d ... 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

Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biologic signatures and predicts patient outcomes.

Journal Article J Am Coll Surg · April 2012 BACKGROUND: Treatment of peritoneal metastases from appendiceal and colon cancer with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) shows great promise. Although long-term disease-free survival is achieved in some cases with t ... 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

Beneficial IL28B genotype associated with lower frequency of hepatic steatosis in patients with chronic hepatitis C.

Journal Article J Hepatol · December 2011 BACKGROUND & AIMS: IL28B polymorphisms have been associated with both treatment induced and spontaneous clearance of hepatitis C virus (HCV). We previously found that LDL cholesterol levels were higher in chronic hepatitis C (CHC) patients with the CC geno ... Full text Link to item Cite

Detection of intestinal dysplasia using angle-resolved low coherence interferometry.

Journal Article J Biomed Opt · October 2011 Angle-resolved low coherence interferometry (a/LCI) is an optical biopsy technique that allows for depth-resolved, label-free measurement of the average size and optical density of cell nuclei in epithelial tissue to assess the tissue health. a/LCI has pre ... 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

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

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

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

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

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

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

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

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

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

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

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

Use of the ThinPrep method in bile duct brushings: analysis of morphologic parameters associated with malignancy and determination of interobserver reliability.

Journal Article Diagn Cytopathol · September 2008 Recent work suggests the ThinPrep method can improve diagnostic sensitivity and accuracy in bile duct brushings. However, the proportion of atypical and suspicious diagnoses remains high. The aim of this study was to identify the most useful morphologic fe ... Full text Link to item Cite

Image of the month. Syphilitic proctitis.

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

Image of the month. Syphilitic proctitis.

Journal Article Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · April 1, 2008 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

Spindle-cell lesions of the liver: diagnosis by fine-needle aspiration biopsy.

Journal Article Diagn Cytopathol · August 2001 Rarely, spindle-cell lesions in liver fine-needle aspiration biopsies (FNABs) are encountered. A retrospective review of our experience with lesions that are mesenchymal in origin or appearance was undertaken to elucidate the frequency and spectrum of thes ... Full text Link to item Cite

Long term response in a patient with neoplastic meningitis secondary to melanoma treated with (131)I-radiolabeled antichondroitin proteoglycan sulfate Mel-14 F(ab')(2): a case study.

Journal Article Cancer · May 1, 2001 Even with novel chemotherapeutic agents and external beam radiation therapy, the prognosis of neoplastic meningitis secondary to malignant melanoma is still dismal. The authors report a case study of a 46-year-old white female who presented with progressiv ... Link to item Cite

Abdominal fat pad aspiration biopsy for tissue confirmation of systemic amyloidosis: specificity, positive predictive value, and diagnostic pitfalls.

Journal Article Diagn Cytopathol · March 2001 Abdominal fat pad fine-needle aspiration biopsy (FNAB) is considered the method of choice for confirmation of systemic amyloidosis. Due to our impression that positive results are rare in our FNA service, we retrospectively analyzed our results. Forty-five ... Full text Link to item Cite

Percutaneous fine-needle aspiration of gastrointestinal wall lesions with image guidance.

Journal Article Diagn Cytopathol · January 2001 The fear of complications related to transgression of the bowel wall has limited the application of fine-needle aspiration (FNA) in gastrointestinal wall masses. We have undertaken a study examining our use of image-guided FNA in this setting, and evaluate ... Full text Link to item Cite

Fine needle aspiration biopsy of the liver.

Journal Article Adv Anat Pathol · November 1999 The liver is a commonly targeted deep-seated organ in which fine-needle aspiration biopsy (FNAB) is performed. By far, the most frequently encountered lesions on FNAB of the liver are metastases; however, a wide variety of other lesions have been described ... Full text Link to item Cite

Rhabdoid tumors of the kidney in children: CT findings.

Journal Article AJR Am J Roentgenol · March 1995 OBJECTIVE: The purpose of this study was to identify CT characteristics of rhabdoid tumor of the kidney, a rare, aggressive, malignant neoplasm of unknown origin that occurs mainly in infants and young children. MATERIALS AND METHODS: CT scans of eight chi ... Full text Link to item Cite