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

Publication ,  Journal Article
Moylan, CA; Pang, H; Dellinger, A; Suzuki, A; Garrett, ME; Guy, CD; Murphy, SK; Ashley-Koch, AE; Choi, SS; Michelotti, GA; Hampton, DD ...
Published in: 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 compared hepatic gene expression profiles in high- and low-risk NAFLD patients to identify processes that distinguish the two groups and hence might be novel biomarkers or treatment targets. Microarray analysis was used to characterize gene expression in percutaneous liver biopsies from low-risk, "mild" NAFLD patients (fibrosis stage 0-1; n = 40) and high-risk, "severe" NAFLD patients (fibrosis stage 3-4; n = 32). Findings were validated in a second, independent cohort and confirmed by real-time polymerase chain reaction and immunohistochemistry (IHC). As a group, patients at risk for bad NAFLD outcomes had significantly worse liver injury and more advanced fibrosis (severe NAFLD) than clinically indistinguishable NAFLD patients with a good prognosis (mild NAFLD). A 64-gene profile reproducibly differentiated severe NAFLD from mild NAFLD, and a 20-gene subset within this profile correlated with NAFLD severity, independent of other factors known to influence NAFLD progression. Multiple genes involved with tissue repair/regeneration and certain metabolism-related genes were induced in severe NAFLD. Ingenuity Pathway Analysis and IHC confirmed deregulation of metabolic and regenerative pathways in severe NAFLD and revealed overlap among the gene expression patterns of severe NAFLD, cardiovascular disease, and cancer. CONCLUSION: By demonstrating specific metabolic and repair pathways that are differentially activated in livers with severe NAFLD, gene profiling identified novel targets that can be exploited to improve diagnosis and treatment of patients who are at greatest risk for NAFLD-related morbidity and mortality.

Duke Scholars

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Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

February 2014

Volume

59

Issue

2

Start / End Page

471 / 482

Location

United States

Related Subject Headings

  • Transcriptome
  • Tissue Array Analysis
  • Severity of Illness Index
  • Risk Factors
  • Prognosis
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Metabolism
  • Male
  • Liver Regeneration
 

Citation

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Moylan, C. A., Pang, H., Dellinger, A., Suzuki, A., Garrett, M. E., Guy, C. D., … Diehl, A. M. (2014). Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease. Hepatology, 59(2), 471–482. https://doi.org/10.1002/hep.26661
Moylan, Cynthia A., Herbert Pang, Andrew Dellinger, Ayako Suzuki, Melanie E. Garrett, Cynthia D. Guy, Susan K. Murphy, et al. “Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease.Hepatology 59, no. 2 (February 2014): 471–82. https://doi.org/10.1002/hep.26661.
Moylan CA, Pang H, Dellinger A, Suzuki A, Garrett ME, Guy CD, et al. Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease. Hepatology. 2014 Feb;59(2):471–82.
Moylan, Cynthia A., et al. “Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease.Hepatology, vol. 59, no. 2, Feb. 2014, pp. 471–82. Pubmed, doi:10.1002/hep.26661.
Moylan CA, Pang H, Dellinger A, Suzuki A, Garrett ME, Guy CD, Murphy SK, Ashley-Koch AE, Choi SS, Michelotti GA, Hampton DD, Chen Y, Tillmann HL, Hauser MA, Abdelmalek MF, Diehl AM. Hepatic gene expression profiles differentiate presymptomatic patients with mild versus severe nonalcoholic fatty liver disease. Hepatology. 2014 Feb;59(2):471–482.
Journal cover image

Published In

Hepatology

DOI

EISSN

1527-3350

Publication Date

February 2014

Volume

59

Issue

2

Start / End Page

471 / 482

Location

United States

Related Subject Headings

  • Transcriptome
  • Tissue Array Analysis
  • Severity of Illness Index
  • Risk Factors
  • Prognosis
  • Non-alcoholic Fatty Liver Disease
  • Middle Aged
  • Metabolism
  • Male
  • Liver Regeneration