Abstract
BACKGROUND: A mass of visceral adipose tissue is one of the most important determinants of progressive liver injury in nonalcoholic fatty liver disease (NAFLD). In accordance, nonalcoholic steatohepatitis (NASH) and fibrosis are believed to occur more commonly in morbidly obese patients compared with nonobese NAFLD patients. AIM OF THE STUDY: Comparative analysis of NAFLD histopathologic features and angiogenesis activity in morbidly obese and nonobese subjects. MATERIALS AND METHODS: Biopsy samples from 40 severely obese (BMI ≥40 kg m(-2)) and 30 nonobese (BMI ≤30 kg m(-2)) NAFLD patients were examined. Kleiner's classification was used to diagnose NASH by grading steatosis, cytoplasmatic ballooning of hepatocytes, and lobular inflammation. The severity of fibrosis was evaluated according to the liver fibrosis staging system. Qualitative and quantitative immunohistochemical analyses of VEGF A, Flk-1, and CD34 were performed to study angiogenesis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was used to study hepatocyte apoptosis. RESULTS: Severely obese patients did not differ from nonobese patients with respect to age and sex distribution. NASH was diagnosed in nine (22.5%) severely obese patients and in seven (23.3%) nonobese patients. Fibrosis was more common in morbidly obese patients (82.5 vs. 43.5%, χ(²) = 11.71, p = 0.003) and was not associated with NASH. Moreover, the severity of fibrosis was greater in obese patients, as advanced fibrosis (bridging fibrosis and cirrhosis) occurred in six (15%) severely obese patients and in two (6.7%) nonobese patients. In morbidly obese individuals, angiogenesis was independent of NASH and was activated at the stage of simple steatosis. In severe obesity, there was a positive relationship between the stage of fibrosis and angiogenic activity. CONCLUSION: In severely obese patients, fibrosis is probably promoted by mechanisms independent of NASH. In these patients, angiogenesis is activated early in the natural history of NAFLD and correlates with the severity of fibrosis.