Seronegative Chronic Hepatitis C Virus Infection
Seronegative Chronic Hepatitis C Virus Infection
ABSTRACT & COMMENTARY
Source: Maggiore G, et al. Antibody-negative chronic hepatitis C virus infection in immunocompetent children. J Pediatr 1998;132:1048-1050.
Maggiore and colleagues in pavia report two apparently immunocompetent children with chronic hepatitis C viremia who had no detectable antibody to this flavivirus. One was a 13-year-old girl whose only known potential exposure was the receipt of immunoglobulin imtramuscularly at 1 year of age. Although asymptomatic, she was found to have persistently elevated serum transaminase levels, and liver biopsy revealed abnormalities consistent with chronic viral hepatitis. Although no antibody to hepatitis C virus (HCV) could be detected using a third-generation assay, HCV RNA was repeatedly detected in plasma. Antibody to HCV E2 viral envelope polypeptide was not detectable. The patient did not have hypogammaglobulinemia and was HIV-1 seronegative. Her virus was genotype 1b.
A 14-month-old boy, who had received red blood cell transfusions as a neonate because of anemia, was found to have elevated serum aminotranferase levels. Third-generation ELISA and RIBA-3 for HCV were each negative, but plasma HCV RNA was detected on two of three occasions over an eight-month period. Anti-HCV by third-generation ELISA was undetectable in the donated blood and in both parents.
COMMENT BY STAN DERESINSKI, MD, FACP
Maggiore et al define seronegative HCV infection as "the presence of HCV viremia, as determined by at least two PCR determinations during a six-month period, in the absence of a serologic response to HCV polypeptides incorporated in a third-generation assay." Seronegative HCV infection is infrequent but is not rare, especially among immunocompromised patients. It has been reported to occur in 15% of children who are long duration survivors of leukemia; these children were infected prior to the screening of blood products with HCV-specific tests.1 Some HIV-infected and hemodialysis patients, as well as some recipients of orthoptic liver transplants, may also fail to mount a serological response to HCV detectable with the available commercial reagents.
These assays detect antibody responses to the core (C), and nonstructural NS3, NS4, and NS5 antigens of HCV. E1 and E2, not contained in commercial assays, are envelope proteins that are also immunogenic. In one study, 3.4% of individuals with seronegative HCV infection had antibody to E2.2 Separately, nine (10.6%) of 85 anti-HCV seronegative (by ELISA) chronic hemodialysis patients had antibody to E2, and six of the nine had detectable viremia.3
The implications of seronegative HCV infection for clinical practice are great. Should assays for plasma HCV RNA be performed in all HCV seronegative immunocompromised patients with persistent elevation of serum transaminase concentrations, in the absence of an alternative explanation for the abnormality? Many health care workers have become aware of the frequent delayed seroconversion after transmission of HCV, a time which can be thought of as a (usually) temporary period of seronegative HCV infection. These exposed health care workers are now requesting that instead of monitoring them for seroconversion, they be monitored with repeated assays for plasma HCV RNA. Should we accede to this request?
References
1. Arico M, et al. Hepatitis C infection in children treated for acute lymphoblastic leukemia. Blood 1994;84: 2919-2922.
2. Cerino A, et al. Antibody responses to the hepatitis C virus E2 protein: Relationship to viremia and prevalence in anti-HCV seronegative subjects. J Med Virol 1997;51:1-5.
3. Lee DS, et al. Significance of anti-E2 in the diagnosis of HCV infection in patients on maintenance hemodialysis: Anti-E2 is frequently detected among anti-HCV antibody-negative patients. J Am Soc Nephrol 1996; 7:2409-2413.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.