title: Autoantibodies in alcoholic liver disease.
abstract: Despite many decades of research, the reasons why only a relatively small proportion of individuals who consume excessive quantities of alcohol develop clinically significant liver disease remain unknown. The association with features of autoimmune diseases, including hypergammaglobulinaemia, circulating autoantibodies, inheritance of certain immunogenetic (HLA) markers and response to corticosteroid therapy in some patients has led to a persistent impression that altered immune regulation with a relative loss of self-tolerance underlies susceptibility to the development of the more severe forms of alcoholic liver disease (alcoholic hepatitis and/or cirrhosis). However, review of the data from the numerous studies that have been conducted over the past 30 years fails to reveal sufficiently convincing evidence that autoimmunity plays a primary role in alcohol-related liver damage. In particular, most of the wide range of circulating autoantibodies that have been reported in patients are found mainly at low titres, are not confined to those with severe liver injury, and are probably more likely to be a response to the hepatic insult than causally related to liver damage. Additionally, an association with various HLA phenotypes has not been confirmed by meta-analysis. Interpretation is complicated by evidence that alcohol may have direct effects on some components of the immune system but, if there is an immunogenetic basis for alcoholic liver disease, the present evidence suggests that this might be related more to cytokine gene polymorphisms than to a predisposition to autoimmunity per se.
authors.affiliation: Institute of Liver Studies, King's College Hospital, London, UK. ian.mcfarlane@kcl.ac.uk
authors.forename: I G
authors.initials: IG
authors.lastname: McFarlane