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.