Autoimmunity and the female liver

In common with several other autoimmune diseases, there is a marked female preponderance in both autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC). Whether this is due to gender differences relating specifically to the liver or more generally to the female constitution is unknown. The clinical expression of these disorders provides few clues to explain their predilection for females. Sexual dimorphism in the metabolic functions of the liver is well recognised, and several studies have suggested that donor-recipient gender matching/mismatching has a major impact on the outcome of orthotopic liver transplantation (OLT) but, overall, the available evidence does not support the concept that the female liver is inherently more susceptible to immune mediated damage. Since the majority of patients present peri-menopausally and endocrinopathy is frequently associated with these conditions, it seems more likely that hormonal factors may be involved. Review of the available information about hormonal effects on the immune system and how they might impact on what is known about the pathogenetic mechanisms, and interact with genetic factors, in the two conditions unfortunately provides no definitive explanation for the predilection of these disorders for females. However, this is clearly a potentially fruitful area for further research.