Spontaneous Viral Clearance Following Acute Hepatitis C Infection: A Systematic Review of Longitudinal Studies

J. M. Micallef; J. M. Kaldor; G. J. Dore


J Viral Hepat. 2006;13(1):34-41. 

In This Article

Summary and Introduction

A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely. To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies. Factors associated with viral clearance were also examined. Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C. Information on study population, and factors that may influence viral clearance were extracted from each study. Viral clearance was defined among individuals with at least 6 months follow-up following acute hepatitis C. The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated. A total of 31 studies were examined. Study populations included nine studies of post-transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero-incident cases. In total, data was available for 675 subjects and the mean study population was 22 (range 4–67). The proportion with viral clearance ranged from 0.0 to 0.8, with a weighted mean of 0.26 (95% CI 0.22–0.29). Factors associated with viral clearance were female gender and acute clinical hepatitis C study population. Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies.

Soon after the hepatitis C virus (HCV) was identified, a number of cross-sectional studies in people with antibodies to the virus demonstrated that some appeared to have spontaneously cleared the infection, while others maintained a state of viraemia, that was subsequently defined as chronic hepatitis C infection.[1–3] Since then, a number of investigators have endeavoured to characterize the pathogenesis of hepatitis C infection, including the rate, time course and predictors of spontaneous viral clearance.[4–11] Estimates of clearance rates have ranged from 10 to 50%,[4–6] and the duration of time to clearance has been found to be as long as 3 years in some cases.[7] Authoritative clinical reviews have generally quoted clearance rates as low as 10–15%.

Factors proposed as being associated with viral clearance in various studies include ethnicity,[7,8] icteric clinical presentation,[7] absence of HIV infection,[8] short incubation period,[12] rapid decline in HCV RNA levels,[13] specific HLA type II alleles,[14,15] and the strength and pattern of HCV-specific CD4 cell responses.[16–19]

Interpretability of findings from most studies of viral clearance in acute hepatitis C infection has been limited by the small numbers of reported cases. The largely asymptomatic nature of acute infection has made it difficult to identify cases for investigation, particularly as they are commonly associated with injecting drug use, illegal and stigmatized behaviour, in many countries.[20–22] In order to provide more precise estimates of viral clearance rates, and better define the factors that predict clearance, we undertook a systematic review of acute hepatitis C studies.


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