The virological and histological states of anti-hepatitis C virus–positive subjects with normal liver biochemical values



We investigated anti-hepatitis C virus (HCV) titers, HCV RNA levels in liver and serum, genetic variability in the hypervariable region of the genome, the form of the virus in the circulation, and liver histology in 21 anti-HCV-positive subjects with sustained normal liver biochemical values. Titer of anti-HCV was determined by second generation anti-HCV-passive hemagglutination assay, and HCV RNA levels were semiquantitated by reverse transcriptase polymerase chain reaction (PCR). In 19 (90%) of the 21 subjects who had a higher titer of anti-HCV (⩾214), HCV RNA was detected in both serum and liver, and histological examination showed minimal or mild chronic hepatitis in all. In the remaining 2 patients who had a lower titer of anti-HCV, HCV RNA was not detected in serum and liver, and liver histology was normal. Anti-HCV titers and HCV RNA levels in serum and liver in the 19 HCV RNA-positive subjects were compared with those levels in the 41 patients with biopsy-proven chronic hepatitis C and elevated serum aminotransferase levels as a control group. There were no significant differences in viral levels in serum and liver between the two groups. To further investigate virological differences between the two groups with regard to degree of genetic variability and the form in the circulation, we performed the PCR-single strand conformation polymorphism (PCR-SSCP) of the hypervariable region 1 and the immunoprecipitation analyses. PCR-SSCP showed that the anti-HCV-positive subjects with normal liver biochemical values had quasispecies nature of the HCV genome similar to the patients with chronic hepatitis C, and the immunoprecipitation analysis showed that the virus circulated both in immune complexes and in the free form in both groups. These findings indicated that both groups had similar virological characteristics but showed different patterns of serum aminotransferase levels and histological findings, suggesting that the two groups may have different immune responses to the virus. (Hepatology 1995; 22: 418–425.)