PATTERNS OF ANTIBODIES TO HEPATITIS-C VIRUS IN PATIENTS WITH CHRONIC NON-A, NON-B HEPATITIS AND THEIR RELATIONSHIP TO VIRAL REPLICATION AND LIVER-DISEASE

Patients with hepatitis C virus infection may have circulating antibodies to various structural and nonstructural antigens of the virus. To assess whether the antibody profile is related to epidemiological or clinical features of chronic infection or to viral replication, sera from 172 consecutive patients with biopsy-proven chronic non-A, non-B hepatitis were studied for antibodies to nonstructural and structural hepatitis C virus antigens and for serum hepatitis C virus RNA with the polymerase chain reaction using primers derived from the 5' noncoding region. Three subgroups could be identified on the basis of their seroreactivity to hepatitis C virus: 133 cases (77.3% [group A]) were positive on first- and second-generation assays and had antibodies to C 100-3 and to C22, C33c or both identified on recombinant immunoblot assay; 23 cases (13.4% [group B]) were positive only on second-generation assay and reacted with C22, C33c or both but not with C 100-3; and 26 cases (9.3% [group C]) were negative for all hepatitis C virus antibodies. Mean age and sex distributions were similar among the three groups; a history of transfusion was more frequent among cases in group B (p = 0.06). These patients also had the highest serum aminotransferase values (p = 0.001). Liver histological studies showed active necroinflammatory changes in 69.2% of patients in group A and 52.2% of those in group B but only in 25% of cases in group C. Serum hepatitis C virus RNA was frequently detected in patients of groups A and B, independent of their recombinant immunoblot assay profiles. Hepatitis C virus RNA was also detected in 5 7% of cases with indeterminate patterns of reactivity on recombinant immunoblot assay. However, none of the patients without hepatitis C virus antibody reactivity had detectable hepatitis C virus RNA in serum. These results identify different subgroups of patients with chronic hepatitis C and indicate that chronic non-A, non-B, non-C hepatitis does exist in our region and that it appears to cause less severe liver injury than does documented hepatitis C.