Molecular connections between non-alcoholic fatty liver disease (NAFLD), NASH and steatohepatitic HCC (SH-HCC)

Sasha Stoddard

Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome and is a growing cause of liver disease. Global prevalence of NAFLD is currently at 25%, and is expected to increase as a major public health concern due to the current worldwide obesity epidemic. The spectrum of NAFLD includes nonalcoholic steatohepatitis (NASH) and steatohepatitic hepatocellular carcinoma (SH-HCC). Not all patients with NAFLD progress to NASH, and the diagnosis and grading of NAFLD/NASH is dependent on the "gold standard" of liver biopsy, an invasive procedure which is also not ideal for screening populations. Molecular mechanisms behind the development and progression of this disease are poorly understood, and this study attempts to correlate serum biomarkers and adipocyte gene expression with quantified fibrotic liver changes in NAFLD patients.

Liver biopsies from obese non-NAFLD, NAFLD, and NASH patients previously diagnosed by a single histopathologist will be analyzed via computerized morphometry as a novel and sensitive approach to quantify levels of steatosis and fibrosis. Immunoassays of serum samples will be performed on key cytokines and proteins implicated as markers for NAFLD such as IL-13, FABP4, and COL4A1. RNA of adipose tissue from the same patients will be extracted and relative gene expression levels analyzed for further understanding of this disease process. Correlation of serum biomarker levels with amount of fibrosis as determined by computerized morphometry will be analyzed to assess potential biomarkers for use as a diagnostic or prognostic tool.