PREVALENCE AND SEROLOGICAL MANIFESTATION OF HEPATITIS-C VIRUS-INFECTION IN PATIENTS WITH HEPATITIS NON-A, NON-B - A FOLLOW-UP-STUDY

Objectives: Sera of patients with acute hepatitis non-A, non-B prospectively followed for a mean of 11.4 years (range 9 to 15 years) were assayed for anti-hepatitis C virus (HCV) by first- and second-generation enzyme-linked immunosorbent assay (ELISA) and second-generation recombinant immunoblot assay (RIBA) to study the patterns of antibody response in relation to the outcome of disease. Methods: From 1974 through 1981, 112 patients with acute hepatitis non-A, non-B were enrolled in a prospective study. Sera of 45 patients taken during the acute phase of hepatitis, as well as taken during follow-up in 1983 and 1990 were still available for evaluation. Sera were assayed by first- (ELISA-1) and second-generation (ELISA-2) anti-HCV ELISA, second-generation RIBA (RIBA-2) and HCV RNA by RT-polymerase chain reaction (PCR). Results: Based on anti-HCV seropositivity by RIBA-2 in acute hepatitis and/or during follow-up, a total of 22/45 patients with HNANB (48.8%) were considered to have confirmed HCV infection. By ELISA-1, 11/22-patients with HCV infection (50%) were positive for anti-HCV within 6 weeks of the onset of illness, 18/22 sera (82%) were reactive by ELISA-2. Confirmation by RIBA-2 was obtained in 12 (55%) cases, while one additional patient was RIBA-2 indeterminate. In 1983, a disappearance of anti-HCV tested by RIBA-2 was observed in 7/12 resolved patients but in none of the patients with chronic hepatitis (p = 0.0018) while loss of anti-HCV was observed in 2/12 cases with resolved hepatitis and none with chronic hepatitis by ELISA (not significant). In 1990, all patients with chronic hepatitis were still positive by either ELISA or RIBA-2 but 9/12 (75%), 6/12 (50%) and 10/11 (91%) patients with resolved hepatitis had lost anti-HCV serepositivity tested by ELISA-1 (p = 0.0004), ELISA-2 (p = 0.0124) or RIBA-2 (p < 0.0001), respectively. Mostly, RIBA-2 reactivity was lost prior to ELISA-2 reactivity during follow-up. Rates of antibody loss as detected by ELISA-1, EL1SA-2 and RIBA-2 were 4.1, 2.9 and 5.8 per 100 person years, respectively. Conclusions: This study shows that the continuing presence of HCV is necessary to maintain anti-HCV seropositivity. In contrast, anti-HCV reactivity is progressively lost over time in resolved patients. In addition, albeit more specific, the RIBA-2 is less sensitive than the ELISA and RIBA seroconversion to negative seems to be the earliest serological marker of a resolved HCV infection.