Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response.

Spontaneous clearance of hepatitis C virus (HCV) has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100,000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

High rate of spontaneous clearance of acute hepatitis C virus genotype 3 infection.

Treating acute hepatitis C with interferon alpha prevents chronicity in nearly all cases when therapy is initiated within 3 months after infection. However, 15-50% of untreated patients may clear the hepatitis C virus (HCV) spontaneously. Therefore, factors are needed to identify patients prior to therapy who have a higher or lower risk for developing a chronic course to avoid unnecessary treatment. The role of the HCV genotype for spontaneous recovery from acute hepatitis C has been discussed controversially. In the year 2002, all 1,176 new incoming prisoners in a Northern German prison for young men (age 16-24) were screened for anti-HCV antibodies and 92 tested positive. Ninety eight percent of these reported i.v.-drug abuse for a median of 32 months prior to imprisonment. HCV-RNA negative individuals (21%) were serotyped and HCV-RNA positive patients were genotyped. The prevalence of HCV genotype 3 was significantly higher among individuals who had cleared HCV spontaneously as compared to chronically infected patients (86% vs. 38%; P = 0.002). Ninety three percent of individuals exposed to HCV genotype 1 but only 63% of individuals exposed to genotype 3 experienced a chronic course of the infection (P = 0.006). Thus, acute infection in young Caucasian men with HCV genotype 3 leads more often to spontaneous clearance than infection with HCV genotype-1. Considering also the high chance of successful treatment of chronic HCV genotype 3 infection with pegylated-interferon in combination with ribavirin, we suggest not to treat acute hepatitis C genotype 3 infection early but rather to wait at least 3 months after the onset of symptoms when chronicity becomes likely.