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

Abstract

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 HCVspecific 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.

Immunological determinants of the outcomes from primary hepatitis C infection

“…The first evidence for this phenotype was the report of sustained viremia and subsequent clearance in association with HCV-specific cellular immune responses, but without seroconversion in high risk Australian prison inmates [194]. This phenotype was confirmed in a subsequent report [195]. Subjects that have undergone viral clearance in such a manner may represent a group with seronegative immune phenotype [196].…”

Selection of high-avidity CD8 T cells correlates with control of hepatitis C virus infection

“…This could reflect prior exposure to HCV along cryptic infection or transient seroconversion. 28,29 Alternatively, because all donors included in our study were not presumably at risk, HCV-specific T cells might also represent memory T cells cross-reactive to other environmental agents. 30,31 Lack of in vitro crossreactivity of HCV-specific T cells to previously described Flu epitopes, which is in agreement with a recent study showing that the NA 231 Flu epitope was a weak agonist for NS3 1073 -specific T cell lines, 32 and enrichment for HCVspecific T cells within the naive compartment in several donors argue against this possibility, but suggest instead a repertoire bias directly linked to positive selection or peripheral homeostatic processes.…”

Occult hepatitis B virus and hepatitis C virus infections

“…In addition, spontaneous seroreversion has been observed during the natural course of HCV infection in the general immune competent population [106] including multitransfused individuals [107]. Furthermore, 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 [108].…”