Characterization of pathogenic and prognostic factors of nonalcoholic steatohepatitis associated with obesity

J Hepatol. 2000 Nov;33(5):716-24. doi: 10.1016/s0168-8278(00)80301-3.


Background/aims: Nonalcoholic steatohepatitis is an emerging clinical problem among the obese population. However, risk factors of progression to advanced forms of liver disease in this particular group of patients remain to be defined.

Methods: The demographics and clinical and histologic features of 46 obese patients were evaluated. The intrahepatic immunological phenotype was assessed in all liver biopsy samples by immunohistochemistry.

Results: Histologic findings of nonalcoholic steatohepatitis were observed in 69.5% of the obese population studied and significant fibrosis was evident in 41% of patients with nonalcoholic steatohepatitis. Age (p=0.003), degree of steatosis (p=0.000002), and grade of inflammation (p=0000) at liver biopsy were independent variables positively associated with fibrosis. Intrahepatic expression levels of several immunologic markers of inflammation as well as nitric oxide derivatives were significantly higher in the severe forms of nonalcoholic steatohepatitis than in the mildest forms.

Conclusions: Obese persons with higher age, with greater degrees of hepatic steatosis, and specially those with increased grades of intrahepatic inflammation have the greatest risk for progression to fibrotic liver disease. An oxidative stress-triggered intrahepatic inflammatory response appears to be important in the pathogenesis of nonalcoholic steatohepatitis in obesity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Antigens, Differentiation, T-Lymphocyte / analysis
  • Endoglin
  • Female
  • Hepatitis / etiology*
  • Hepatitis / immunology
  • Hepatitis / pathology
  • Humans
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / analysis
  • Lectins, C-Type
  • Liver / pathology
  • Liver / physiopathology
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Obesity / complications*
  • Prognosis
  • Receptors, Cell Surface
  • Tyrosine / analogs & derivatives
  • Tyrosine / analysis
  • Vascular Cell Adhesion Molecule-1 / analysis


  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • ENG protein, human
  • Endoglin
  • Lectins, C-Type
  • Receptors, Cell Surface
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • 3-nitrotyrosine
  • Tyrosine
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II