Progressive loss of hepatocyte nuclear factor 4 alpha activity in chronic liver diseases in humans.

ABSTRACT:

Background and aims

Hepatocyte nuclear factor 4 alpha (HNF4α) is indispensable for hepatocyte differentiation and critical for maintaining liver health. Here, we demonstrate that loss of HNF4α activity is a crucial step in the pathogenesis of chronic liver diseases (CLDs) that lead to development of HCC.

Approach and results

We developed an HNF4α target gene signature, which can accurately determine HNF4α activity, and performed an exhaustive in silico analysis using hierarchical and K-means clustering, survival, and rank-order analysis of 30 independent data sets containing over 3500 individual samples. The association of changes in HNF4α activity to CLD progression of various etiologies, including HCV- and HBV-induced liver cirrhosis (LC), NAFLD/NASH, and HCC, was determin

SUBMITTER: Gunewardena S 

PROVIDER: S-EPMC9762158 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature