Significance of Microvesicular Steatosis in Nonalcoholic Fatty Liver Disease (NAFLD)

Abstract

Purpose: NAFLD is associated with accumulation of excess fat in hepatocytes visualized as macrovesicular steatosis. Some patients with NAFLD also have nonzonal aggregates of microvesicular steatosis but its significance is unknown. Diffuse microvesicular steatosis is associated with mitochondrial injury; a factor that plays an important role in the disease progression. We evaluated the frequency of microvesicular steatosis and assessed its association with histologic markers of severity in patients with NAFLD. Methods: All adult patients' biopsies in the NAFLD Database Study or pre-treatment PIVENS Trial in the NASH Clinical Research Network in the US were evaluated in a cross sectional study. Liver biopsies were reviewed centrally by the Pathology subcommittee. Microvesicular steatosis is defined as discrete, nonzonal patches of “foamy” hepatocytes with central nucleus and too numerous to count small droplets of fat. The relationship between microvesicular steatosis and different NAFLD histological features was tested by multiple logistic regression analysis after controlling for age, gender, race, BMI and diabetes. Results: 1022 liver biopsy samples were studied. 102 (10%) had documented microvesicular steatosis. Patients with and without microvesicular steatosis were comparable in age (50.2±12.5 vs. 49.5±11.9 years, p=0.56), female gender (66% vs. 63%, p=0.59), BMI (36.1±7.6 vs. 34.5±6.4 kg/m2, p=0.07) and diabetes (25% vs. 30%, p=0.36). Microvesciular steatosis was associated with higher grades of steatosis and ballooning, presence of Mallory bodies and advanced fibrosis. NAFLD patients with NASH had significantly higher microvesicular steatosis than those without NASH. Conclusion: The presence of microvesicular steatosis in liver biopsies of NAFLD was associated with greater overall degrees of activity and fibrosis. These observations suggest that microvesicular steatosis may play an important role in mediating cell injury and disease progression in NAFLD.Table: Table. Relationship between microvesicular steatosis and different histological features of NASH from multiple logistic regression analysis