Hepatitis Central

Studies in chimpanzees have raised the chilling possibility that blood transfusions may still be transmitting hepatitis C virus.

The animal studies suggest that silent carriers of hepatitis C virus HCV) may represent potentially infectious blood donors.

"An estimated 20 percent of HCV infected humans are expected to convalesce, in contrast to approximately 60 percent of HCV infected chimpanzees in this study," Suzanne E. Bassett and colleagues of the University of Texas Health Science Center wrote ("Analysis of Hepatitis C Virus Inoculated Chimpanzees Reveals Unexpected Clinical Profiles," Journal of Virology, April 1998;72(4):2589-2599).

"If the percentage of chimpanzees that convalesce can be extrapolated to the human population, the frequency of humans that clear the virus may be several times higher than estimated. Since most HCV infections are asymptomatic, and many individuals have normal alanine aminotransferase levels throughout the infection, humans that clear the virus and become antibody negative would not be detected in clinical studies or as HCV exposed blood donors."

Bassett et al. examined the clinical course of HCV infections in a chimpanzee cohort to better characterize the outcome in this valuable animal model. Results of a cross-sectional study revealed that a low percentage (39 percent) of HCV inoculated chimpanzees were viremic based on reverse transcription (RT-PCR) analysis.

A correlation was observed between viremia and the presence of anti-HCV antibodies. The pattern of antibodies was dissimilar among viremic chimpanzees and chimpanzees that cleared the virus. Viremic chimpanzees had a higher prevalence of antibody reactivity to NS3, NS4, and NS5.

Since an unexpectedly low percentage of chimpanzees were persistently infected with HCV, a longitudinal analysis of the virological profile of a small panel of HCV infected chimpanzees was performed to determine the kinetics of viral clearance and loss of antibody.

It was determined that a low percentage (33 percent) of HCV inoculated chimpanzees were persistently viremic. Analysis of serial bleeds from six HCV infected animals revealed four different clinical profiles. Viral clearance with either gradual or rapid loss of anti-HCV antibody was observed in four animals within five months postinoculation.

A chronic-carrier profile characterized by persistent HCV RNA and anti-HCV antibody was observed in two animals. One of these chimpanzees was RT-PCR positive, antibody negative for five years and thus represented a silent carrier.

The authors noted that it was unclear if the lower percentage of chimpanzees with persistent HCV infection compared to the human population was due to differences in the clinical courses or if the full clinical spectrum of HCV infected humans is not observed in studies that select individuals based on disease status and high-risk activities.

"The frequency of HCV infection may also be underestimated in the human population if similarities in antibody profiles exist between humans and chimpanzees that clear the virus," Bassett et al. wrote. "Both rapid and gradual loss of anti-HCV antibody titer was observed in the chimpanzees that cleared the virus. If rapid loss of antibody occurs in the human population, as in the chimpanzees, the duration of time that HCV infection could be detected would be greatly reduced, and the frequency of HCV infection and viral clearance may be underestimated.

"Resolved HCV infections in seronegative humans may he more common than is generally suspected, since the loss of anti-HCV antibody has been observed in HCV infected humans, and since HCV specific cytotoxic T-lymphocyte responses are occasionally detected in the normal control population."

The authors noted that the frequency of HCV infection may also be underestimated if a significant percentage of silent carriers exist within the human population. They added, however, that it is difficult to determine the actual percentage of silent carriers in the human population without performing longitudinal RT-PCR studies on thousands of individuals or at least numerous high-risk individuals.

"Regardless of whether HCV infected chimpanzees are truly representative of HCV infection in humans, the chimpanzee animal model will be valuable in understanding the mechanism of viral clearance," Bassett et al. wrote.

"Early vaccine trials for HCV in chimpanzees attributed clearance of viremia to attenuation of the infection due to partial protection by the vaccine. Such interpretations are surely complicated by the findings presented in this study."

The corresponding author for this study is Robert E. Lanford, Department of Virology and Immunology, Southwest Foundation for Biomedical Research, 7620 N.W. Loop 410, San Antonio, Texas 78228.

- by Salynn Boyles, Senior Editor

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