Soon after the discovery of HCV, high frequencies of anti-HCV (>50%) were reported among patients with autoimmune hepatitis (Esteban et al., 1989; Lenzi et al., 1990) and, later, among patients with other autoimmune diseases (Table 7.1 and Section 1.5). Further work among patients with HCV-associated autoimmune hepatitis showed that many anti-HCV results were caused by false positives generated by hypergammaglobulinemia (McFarlane et al., 1990) and by immune complexes (McFarlane et al., 1983), which interfered with first-generation anti- HCV ELISAs. False-positive anti-HCV results were also noted in patients with other autoimmune diseases (Fusconi et al., 1990), although the frequency of anti-HCV correlated directly with the levels of gammaglobulin in sera (Schwarcz, von Sydow & Weiland, 1990) (Section 1.5). The introduction of second-generation anti-HCV testing and RT/PCR, however, still showed that 20–40% of patients with autoimmune hepatitis had detectable markers of HCV infection (Cassani et al., 1992; Nishiguchi et al., 1992). Independent work showed that the frequency of anti-HCV among patients with primary biliary cirrhosis or primary sclerosing cholangitis was low (<5%) and similar to that of the general population (Lohse et al., 1995), suggesting that HCV infection is not closely linked with autoimmune diseases. Likewise, anti-HCV was found in 3–5% of patients with liver–kidney microsomal autoantibodies (Abuaf et al., 1993), a non-organ specific marker of autoimmunity, although the titers in patients with HCV-associated hepatitis are usually much lower than in patients with autoimmune hepatitis (Strassburg et al., 1996).