Genetics of Autoimmune Liver Disease: A Brief Summary for Clinicians

Abstract

Autoimmune liver diseases are rare chronic immune-mediated liver injuries in which the consequences of hepatic and biliary inflammation are cirrhosis and end-stage liver disease. Epidemiological surveys of individuals, families and populations strongly support a model of disease for which environmental and genetic influences are highly relevant to why any individual develops disease. The overlapping clinical presentations of primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis further highlight the likelihood for shared pathways to disease. Of late, the application of high-throughput genetic technology, paralleled by large patient cohort development, has led to new insights into the nature of the host genetic risk. This risk is now robustly demonstrable for the HLA locus as well as in various non-HLA loci and is summarized in this brief review article.

Association of CARD10 rs6000782 and TNF rs1799724 variants with paediatric-onset autoimmune hepatitis

“…Among the scant literature discussing the onset of paediatric-onset autoimmune hepatitis (pAIH), a recent Chinese study reported an incidence of 0.4 per 100,000 children [6]. Overall, the pathogenesis of AIH remains incompletely understood; however, genetics, represented by single-nucleotide polymorphisms (SNPs), and environmental factors are involved [7]. The most investigated genes are those located within the human leukocyte antigen (HLA) region, though evaluation of the non-HLA genetics of AIH may provide novel targets for diagnosis, treatment, and prevention [8].…”

Review article: experimental therapies in autoimmune hepatitis

“…Autoimmune hepatitis (AIH) manifests as an inflammatory disorder of the liver parenchyma and is associated with hypergammaglobulinaemia, circulating autoantibodies, specific HLA‐DR alleles and characteristic histological changes 1‐5 . AIH may result in a chronic, fluctuating hepatitis, potentially leading to progressive fibrosis, cirrhosis and chronic liver failure.…”