Genomics and proteomics in liver fibrosis and cirrhosis

Liver fibrosis results from a wound-healing response to chronic injury, which leads to excessive matrix, or scar deposition. This scar tissue can restrict blood flow due to contraction of the organ, leading to progressive liver damage and cirrhosis (the end stage of fibrosis), complicated by liver failure, portal hypertension and/or hepatocellular carcinoma [1]. Fibrosis is prominent in chronic liver diseases, including viral hepatitis, alcoholic and non-alcoholic steatohepatitis, toxic liver injury, auto-immune diseases and several genetic diseases. There have been two major priorities for therapy to reduce fibrosis: 1) to establish treatments for the diseases that lead to liver fibrosis; and, 2) to identify agents that directly slow or reverse fibrogenesis independent of the underlying disease.A key discovery in understanding fibrosis has been the role of hepatic stellate cells (HSCs), vitamin A storing cells in the space of Disse, which, when activated, transform into myofibroblast-like cells, shedding their vitamin A content, and producing fibrogenic proteins, including collagens and tissue inhibitor of metalloproteinases-1 (TIMP-1) [2]. This review will focus on the contribution of high-throughput genomic and proteomic approaches to the study of fibrogenesis and fibrosis progression, concentrating on the most prevalent human chronic liver diseases and findings from animal models in liver tissue, isolated liver cells, cell lines and serum.Genetic diseases can be classified as chromosomal abnormalities (for example, trisomy 21), Mendelian disorders (single gene alterations with typical inheritance patterns, like autosomal dominant/recessive or X-linked), and complex diseases that are influenced by many genetic and environmental components. Degenerative diseases like liver fibrosis are complex illnesses [3]. The genetic contributions to these disorders are not attributable to a single gene alteration, but rather to a host of genetic susceptibilities defined by sin