[Genetic risk factors for hepatic fibrosis in chronic liver diseases]

Hepatic fibrosis is the result of chronic viral, toxic, autoimmune, or cholestatic liver injury. During the complex fibrotic response, hepatic stellate cells transdifferentiate into matrix-producing myofibroblasts, and interactions between multiple cytokines, receptors and extracellular matrix components modulate the fibrotic phenotypes. Of note, course and extent of hepatic fibrosis display significant variability among individual patients. These well-known differences in progression of hepatic fibrosis have been attributed to age, sex, and exogenous factors, e. g., coinfections or alcohol consumption. However, host genetic factors are likely to play key roles in the modulation of hepatic fibrosis and to contribute to the overall variability in disease progression. In recent years, different genetic polymorphisms that may influence the progression of hepatic fibrosis have been identified in animal models and human case-control studies. These findings indicate that variants of genes encoding immunoregulatory proteins as well as pro- and anti-inflammatory cytokines determine liver fibrosis in patients with chronic hepatitis C virus infection, alcoholic liver disease, and autoimmune liver diseases. However, the results of these studies are mixed and restricted to selected known genes. Therefore, definition of consensus criteria for association studies and multicenter studies are needed to increase statistical power. Genome-wide scans in experimental animal crosses should be employed to identify unknown gene loci that confer susceptibility to hepatic fibrosis (Hfib loci). In conclusion, genetic association studies have a great potential for identification of fibrogenic genes, but large-scale, well-designed studies are required to clarify their actual relevance and to provide a solid framework for future therapeutic strategies.