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.