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Suppression of hepatitis C virus (HCV) replication by hepatitis D virus (HDV) in HIV-infected hemophiliacs with chronic hepatitis B and C
Authors:Dr M Elaine Eyster MD  Jeffrey C Sanders MS  Manuel Battegay MD  Adrian M Di Bisceglie MD
Institution:(1) Division of Hematology, Department of Medicine, Pennsylvania State University School of Medicine, Hershey, Pennsylvania;(2) The Liver Diseases Section, National Institute of Digestive Diseases and Kidney, National Institutes of Health, Bethesda, Maryland;(3) Milton S. Hershey Medical Center, P.O. Box 850, 17033 Hershey, Pennsylvania
Abstract:Most hemophiliacs who are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have high serum levels of HCV RNA. To study the impact of multiple hepatitis virus infections, we evalated all eight chronic carriers of hepatitis B surface antigen (HBsAg) from a previously studied cohort of 99 hemophiliacs with chronic HIV and HCV infections. Stored serum or plasma samples were tested for antibody to hepatitis D virus (anti-HDV) by ELISA; qualitatively for HCV RNA, HBV DNA, and HDV RNA by the polymerase chain reaction (PCR); and quantitively for HIV RNA, HCV RNA, and hepatitis B virus (HBV) DNA by a quantitative branched DNA signal amplification assay. HCV RNA was detected in only one of five patients with HDV infections on a cross-sectional study, and this individual had low levels (<3.5×105 genome eq/ml) of HCV RNA. In contrast, all three without HDV infections had high levels (>1.5×107 genome eq/ml) of HCV RNA. HIV RNA was present in all eight patients. There was no correlation between the level of HIV RNA and the presence of hepatitis viruses. Three of the eight patients (38%) died of liver failure and another has hypersplenism with hypoprothrombinemia. We conclude that HDV infection appears to suppress HCV replication and that liver failure is common in adult HIV-infected hemophiliacs with chronic HCV and HBV infections. These findings have implications for the therapy of HCV-infected hemophiliacs who are HBsAg positive.This study was supported by the Brandywine Valley Hemophilia Foundation, and the Alice Livingston Trout Family Fund.Dr. Battegay was supported by the Swiss National Science Foundation, the Conrad Gessner Stipendium, and the Schweizerische Stiftung fur medizinisch biologische stipendien.
Keywords:hepatitis C  HIV  hepatitis D  delta virus  hepatitis B  hemophilia  liver failure
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