HEPATITIS-C VIRUS IN AUTOIMMUNE LIVER-DISEASE IN THE UK - ETIOLOGIC AGENT OR ARTIFACT

Hepatitis C virus antibody titres (anti-HCV) were measured in serum fr om 122 patients with autoimmune liver disease (96 with primary biliary cirrhosis and 26 with autoimmune chronic active hepatitis using three generations of enzyme immunoassay (EIA): first generation - Ortho, EI A1; second generation - Abbott, EIA2; and third generation - Murex, EI A3. Anti-HCV was below the positive cut-off level in all 26 autoimmune chronic active hepatitis patients for all tests, while seropositivity values in primary biliary cirrhosis were 31% (EIA1), 14% (EIA2), and 0% (EIA3). In primary biliary cirrhosis, anti-HCV values as measured b y all three tests correlated positively with serum IgG concentrations, serum storage time, and a number of other indices of hepatic dysfunct ion. Multiple regression analysis showed that anti-HCV values were ind ependently affected by both serum IgG and the length of storage time, although the magnitude of the effects varied between tests. When all t hree multiple regression models were applied to an extreme clinical ex ample, however, EIA3 was least likely to give a false-positive result. The difference in test performance was emphasised further by examinat ion of anti-HCV values in nine primary biliary cirrhosis patients (con firmed negative by recombinant immunoblot assay 2) in whom serial samp les were tested (seven to 14 per patient, stored for one to 138 months ). Apparent anti-HCV values (EIA1 and EIA2) increased with increasing serum storage time, but were unchanged when measured by EIA3. A simila r pattern was evident in a limited study of five autoimmune chronic ac tive hepatitis patients. Thus, in the largest study reported to date, there is no evidence of an important aetiological role for HCV in auto immune chronic active hepatitis or primary biliary cirrhosis in the UK . The third generation of anti-HCV EIAs is the most reliable screening test, will avoid costly and unnecessary confirmatory testing, and may partly clarify the existing geographical heterogeneity in anti-HCV se roprevalence. An accurate diagnosis of past HCV infection is an import ant determinant in the choice of treatment in autoimmune chronic activ e hepatitis. As the second generation EIA is in widespread use and con firmatory testing is not always available, the effect of serum storage in addition to hyperglobulinaemia should be considered in the interpr etation of positive results in autoimmune and in other types of chroni c liver disease.