Prospective study of hepatitis C viral load after community-acquired infection

Hepatitis C virus (HCV) infection generally results in chronic hepatitis. However, the dynamics of viral replication after acute infection and the frequency of persistence are poorly understood. Between 1988 and 1996, new HCV infections were identified and followed semiannually in a prospective study of Baltimore injection drug users. HCV seroconversion was detected in 43 persons, all of whom were also HCV RNA positive. To prospectively assess viral dynamics, serum HCV RNA was measured by quantitative PCR (Roche Molecular Systems) in a median of 9 samples per subject. HCV RNA was persistently detectable in 37 cases (86%), of which 5 had one or two transiently undetectable levels. In 6 individuals (14%), HCV RNA was detected (median duration of RNA detection after seroconversion =18.5 months), then fell and remained below the level of detection (500 copies/mL) for a median of 40 months. HCV antibody remained detectable in all subjects. There were no elevated serum ALT levels among the 6 subjects after HCV clearance, whereas 46% of those with RNA persistence had abnormal ALTs (p<.05). The peak and first HCV viral load levels were higher among the 37 persons with RNA persistence, compared to the 6 with apparent clearance (p=.01 and .09, respectively), although the duration of follow-up after seroconversion was similar (74 vs 68 months; p >.10). Approximately 15 percent of individuals with community-acquired hepatitis C appear to clear viremia and have no subsequent biochemical evidence of liver disease. Further investigation of acute infection may elucidate the basis for viral persistence and suggest predictors of clearance or response to treatment.