Genetic Determinants in Hepatic Fibrosis: From Experimental Models to Fibrogenic Gene Signatures in Humans

Hepatic fibrosis, or scarring of the liver, is a nonspecific reaction to chronic liver injury. Hepatic fibrosis is commonly caused by exogenous factors such as viral hepatitis or alcohol abuse, but recent studies also indicate a genetic predisposition. Although some patients who have chronic liver diseases show only minor morphologic and functional alterations of the liver and are characterized by slow progression of disease with mild clinical symptoms, others develop pronounced hepatic fibrosis rapidly, culminating in cirrhosis, liver failure, or hepatocellular carcinoma, respectively. These well known differences in progression of hepatic fibrosis persist when controlling for age (at infection), gender, and exogenous factors in multivariate analysis, indicating that genetic factors might play important roles in the modulation of hepatic fibrosis and contribute to the variability in fibrosis progression. This review summarizes genetic determinants in hepatic fibrosis.