Autoimmunity and extrahepatic manifestations in hepatitis C virus infection

Hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations: mixed cryoglobulinaemia, membranoproliferative glomerulonephritis and, in southern Europe, to some extent with porphyria cutanea tarda. The association of haplotype HLA B-8 and DR-3 mixed cryoglobulinaemia and HCV infection has recently been demonstrated. Interferon alpha therapy decreases hepatitis C viraemia and improves the clinical signs and biochemical abnormalities of cryoglobulinaemia. There seems to be a south-north gradient in the prevalence of HCV-associated cryoglobulinaemia. The rare combination of hepatitis C and panarteritis nodosa has still not been confirmed. The sicca syndrome also seems to be associated with hepatitis C virus, but this is not the typical Sjogren syndrome. Existing studies have not answered the question of whether HCV plays a pathogenic role in the development of thyroid dysfunction and autoimmune thyroiditis. There seems to be a genetic predisposition for the manifestations of thyroid disease in the case of hepatitis C infection and interferon therapy. This predominantly affects women with haplotype HLA DR-3. Before beginning interferon therapy, these patients often show thyroid autoantibodies against the thyroid peroxidase and/or thyroglobulin. It is still unclear whether the rare combination of hepatitis C with aplastic anaemia and lymphoma has pathogenic aspects. These haematological manifestations are thought to be induced by the infection of haematopoetic cells with the hepatitis C virus. In rare cases, a stimulated HCV-induced interferon gamma synthesis by haematopoetic stem cells has been shown. Although an epidemiological association of hepatitis C with lichen planus, neuropathies and other diseases has been observed, the aetiological role and the pathogenic involvement of the hepatitis C infection remains unclear. Furthermore, the question of whether these extrahepatic diseases are autoimmune has not been clarified. On the other hand, a number of autoantibodies may be observed during the course of hepatitis C. Of particular interest are liver/kidney microsomal antibodies (LKM). Their occurrence in viral hepatitis may indicate an increased risk for treatment with interferons. In the clinical setting, the presence of these diseases should suggest hepatitis C infection and hepatitis C antibodies should be tested and, if positive, hepatitis C-RNA is indicated. If there is any evidence of an aetiological association of replicative hepatitis C infection and the above-mentioned extrahepatic diseases, antiviral treatment should be considered.