Liver fibrosis: from animal models to mapping of human risk variants.

Liver fibrosis is the sequel of chronic liver diseases and the main reason for increased mortality in affected patients. The extent of liver fibrosis displays great interindividual variation, even after controlling for exogenous factors. Thus, host genetic factors are considered to play an important role in the process of liver scarring. From a genetic perspective, liver fibrosis is a complex trait with many genes contributing to the expression of the phenotype. In genetically manipulated and inbred animals several risk loci for liver fibrosis have been identified. Some of these loci have been replicated in case-control studies of patients with hepatitis C infection. In humans, genetic risk loci were identified by single marker studies, haplotype studies or the combination of single markers. Recently, the first genome-wide association studies have also been performed in patients with liver diseases. Some of the identified gene variants have been functionally characterized in vitro, thereby opening the potential for novel therapeutic approaches and risk stratification.