Skip to main content
Journal cover image

Mechanisms of disease progression in nonalcoholic fatty liver disease.

Publication ,  Journal Article
Jou, J; Choi, SS; Diehl, AM
Published in: 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 (NASH) is an intermediate level of hepatic pathology. Hepatocyte accumulation of triglyceride is a hallmark of NAFL and NASH, but this sometimes subsides once cirrhosis has developed. Triglyceride storage per se is not hepatotoxic. Rather, it is a marker of increased exposure of hepatocytes to potentially toxic fatty acids. NAFL progresses to NASH when adaptive mechanisms that protect hepatocytes from fatty acid-mediated lipotoxicity become overwhelmed and rates of hepatocyte death begin to outstrip mechanisms that normally regenerate dead hepatocytes. This triggers repair responses that involve activation of hepatic stellate cells to myofibroblasts. The myofibroblasts generate excessive matrix and produce factors that stimulate expansion of liver progenitor populations. The progenitor cells produce chemokines to attract various kinds of inflammatory cells to the liver. They also differentiate to replace the dead hepatocytes. The intensity of these repair responses generally parallel the degree of hepatocyte death, resulting in variable distortion of the hepatic architecture with fibrosis, infiltrating immune cells, and regenerating epithelial nodules. As in other types of chronic liver injury, cirrhosis ensues in patients with NAFLD when repair is extreme and sustained, but ultimately unsuccessful, at reconstituting healthy hepatic epithelia.

Duke Scholars

Published In

Semin Liver Dis

DOI

ISSN

0272-8087

Publication Date

November 2008

Volume

28

Issue

4

Start / End Page

370 / 379

Location

United States

Related Subject Headings

  • Oxidation-Reduction
  • Liver Neoplasms
  • Liver Cirrhosis
  • Liver
  • Insulin Resistance
  • Humans
  • Hepatocytes
  • Gastroenterology & Hepatology
  • Fatty Liver
  • Fatty Acids, Nonesterified
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jou, J., Choi, S. S., & Diehl, A. M. (2008). Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis, 28(4), 370–379. https://doi.org/10.1055/s-0028-1091981
Jou, Janice, Steve S. Choi, and Anna Mae Diehl. “Mechanisms of disease progression in nonalcoholic fatty liver disease.Semin Liver Dis 28, no. 4 (November 2008): 370–79. https://doi.org/10.1055/s-0028-1091981.
Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008 Nov;28(4):370–9.
Jou, Janice, et al. “Mechanisms of disease progression in nonalcoholic fatty liver disease.Semin Liver Dis, vol. 28, no. 4, Nov. 2008, pp. 370–79. Pubmed, doi:10.1055/s-0028-1091981.
Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liver Dis. 2008 Nov;28(4):370–379.
Journal cover image

Published In

Semin Liver Dis

DOI

ISSN

0272-8087

Publication Date

November 2008

Volume

28

Issue

4

Start / End Page

370 / 379

Location

United States

Related Subject Headings

  • Oxidation-Reduction
  • Liver Neoplasms
  • Liver Cirrhosis
  • Liver
  • Insulin Resistance
  • Humans
  • Hepatocytes
  • Gastroenterology & Hepatology
  • Fatty Liver
  • Fatty Acids, Nonesterified