Seroreversion from Hepatitis C after Needlestick Injury

SIR—We read with great interest the case report by Morand et al. [1], which described the lack of seroconversion after early treatment of acute hepatitis C following needlestick injury, despite the normal cellular and humoral responses of the host. Because few reports are available on the course of the immune response to hepatitis C virus (HCV) after early treatment of acute hepatitis C, we present a case report that may contribute to discussion of this topic. In January 1997, a 34-year-old nurse who had tested negative for both HIV and HCV sustained a superficial wound caused by a venipuncture needle. The donor patient was HIV negative, was infected with an HCV isolate of genotype 1a (identified by Inno-LiPA HCV II; InGeN), and had a high virus load (7.00 log10 copies/mL) detected in serum samples (Cobas Monitor HCV; Roche Diagnostic System). Follow-up examination of the nurse included determination of the alanine aminotransferase (ALT) level, monthly testing for HCV RNA by the use of reverse-transcriptase PCR (Cobas Amplicor HCV; Roche Diagnostic System), and anti-HCV testing with the use of 2 third-generation ELISAs (AxSYM HCV, version 3.0 [Abbott Laboratories], and Monolisa HCV Plus [Bio-Rad]). Specific antibody response was analyzed by strip immunoassay (SIA); analysis was done in 1997, by use of the Deciscan assay (Bio-Rad), and then retrospectively, by use of the RIBA HCV 3.0 assay (Chiron). The results of these analyses are shown in table 1. Findings from clinical and biological follow-up of a nurse who had blood exposure to hepatitis C virus (HCV) after a needlestick injury. During the first month after exposure (month 1), HCV RNA was detected in the nurse's serum, and her ALT level increased to up to 3.5 times greater than the normal level. The nurse was found to have the same HCV genotype as the donor patient. Treatment with IFN-α (3 million U given 3 times per week for 3 months) was initiated immediately. Treatment continued pragmatically for a total of 6 months, because HCV RNA was still detectable after 1 month and because it became undetectable only after 3 months of therapy. A prolonged response was obtained; a normal ALT level and the absence of detectable RNA were noted 4 years after the needlestick injury. Anti-HCV antibodies were detected by ELISA only at and after month 2. An isolated reactivity against HCV core protein was detected by RIBA during month 1, and the response increased until month 4. Specific anti–HCV core protein response rapidly decreased at the end of treatment. Four years after the needlestick injury occurred, ELISA reactivity had decreased, SIA reactivity against HCV core protein had disappeared, and SIA reactivity against NS3 and NS4 proteins had decreased (table 1). Evolution of the HCV status showed that the nurse was recovering from her infection. In the case report by Morand et al. [1], complete seroconversion never occurred, despite weak ELISA reactivity at week 5. A short period (1 month) of viral replication was associated with a high ALT level. In our experience, seroconversion occurred and was followed by seroreversion that included a 2–3-month replication period and a transiently moderate elevation of the ALT level. These 2 cases outline the fact that absence of seroconversion or rapid seroreversion is strongly related to quick virus eradication, either spontaneously or with treatment [1–3, 5]; a recent report by Jaeckel et al. [4] supports this finding. Further studies of T cell response in such treated patients might help us improve our understanding of the mechanisms of early virus elimination. In our experience, follow-up with SIA is a useful tool for prognosis. Finally, the sustained response obtained with IFN-α therapy in our patient, despite the persistence of virus replication at 1 month of treatment and a genotype 1a virus, outlines the different virological response profile of primary and chronic infection with HCV. All parameters—virological, biochemical, and immunological—are of importance when making decisions regarding adaptation of postexposure treatment (i.e., type, dose, and duration of treatment). In conclusion, acute hepatitis C is often associated with the absence of seroconversion or seroreversion, as demonstrated by the case reports presented here and elsewhere [1, 3, 4]. This may lead to underestimation of the global prevalence of hepatitis C, and, moreover, the chronic evolution of hepatitis C may be overestimated.