Hepatitis C infection and autoimmunity.

Since the first tests for antibodies to components of the hepatitis C virus became widely available there has been considerable interest in evidence linking HCV infection with autoimmune liver diseases and other autoimmune conditions. With respect to autoimmune hepatitis, it is now clear that the early tests were quite non-specific and that it was the abnormalities in serum globulins in autoimmune hepatitis which led to such high positivity rates in this disease. Careful surveys across Europe have now made it clear that there are true associations between HCV infection and autoimmune liver diseases, but that their frequency is much higher in the south than the north. This is particularly striking for that variety of autoimmune hepatitis positive for antibodies to the liver/kidney microsomal antigen (cytochrome P450 2D6). Here there are distinct subgroups; one a "true" autoimmune group of younger females with more active disease, and a second, containing older patients with a more even sex distribution, where the virus seems to be driving an autoimmune reaction. The mechanisms underlying these associations are not yet clear, although analysis of the amino-acid sequences of selected virus and host proteins has shown some significant homology. Interestingly, and surprisingly, the overall incidence of periportal hepatitis is lower in HCV infection than in acute or chronic HBV infection, or acute HAV hepatitis. There is a parallel distribution in the frequency and titre of antibodies to the asialoglycoprotein receptor, one of the important targets for autoimmune reactions on the liver cell membrane. There are many reports of associations between HCV infection and other immune-mediated conditions, and although the strength of such associations is always difficult to judge, HCV infection in some conditions, such as cryglobulinaemia, is clearly an important driving force. Here, treatment of the HCV infection with interferon may led to striking remission in associated vascular lesions. Clinically, it can be very difficult to distinguish between liver disease due to HCV infection and autoimmune hepatitis co-existing with HCV infection, but because the treatment for these two conditions is quite different, the distinction is important. Alpha-interferon, the current treatment of choice for HCV infection, often induces a relapse in autoimmune hepatitis, while steroids, the treatment of choice for autoimmune hepatitis, may be permissive for HCV replication, and thus, at least in theory, may militate against the success of a subsequent course of alpha-interferon. A pragmatic approach to the choice of a first therapeutic agent is recommended based on the relative local prevalence of the two conditions, the use of readily available clinical tests, and the results of appropriate specialised assays in the most difficult cases.