Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo. NLM AIDSLINE Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

Click here to return to AIDSLINE main menu
DonateNow
Print this Article


Effect of interferon alfa on the dynamics of hepatitis C virus turnover in vivo.

Hepatology. 1996 Feb;23(2):366-71. Unique Identifier : AIDSLINE MED/96162064
Zeuzem S; Schmidt JM; Lee JH; Ruster B; Roth WK; Medizinische Klinik II, Klinikum der Johann Wolfgang; Goethe-Universitat, Frankfurt am Main, Germany.

Abstract: In about 30% to 40% of patients with chronic hepatitis C, treatment with recombinant interferon alfa (r-IFN alpha) causes a decrease of serum aminotransferases and hepatitis C virus (HCV) RNA. The antiviral mechanism of interferon alfa (IFN alpha) in vivo is unknown. From serial measurements of serum HCV-RNA concentrations following IFN alpha induced perturbation of the balance between virus production and clearance, we obtained kinetic information on the pretreatment steady-state of HCV. In patients with chronic hepatitis C responding to IFN alpha, HCV-RNA declined exponentially with a half life of approximately 2 days. Modeling of the data predicts that in patients with chronic hepatitis C responding to IFN alpha this cytokine predominantly acts as an inhibitor of de novo infection of susceptible cells. HCV is released from infected cells with a mean half life of 2.7 +/- 1.3 days, whereas the clearance rate from serum is faster (mean half life, 0.7 +/- 0.4 days). The minimum virus production and clearance per day in patients with chronic hepatitis C was calculated to be 6.7 x 10(10) virions/d (range, 0.2 to 43.8 x 10(10) virions/d). These values showed no correlation with the HCV genotype, aminotransferase levels, or the histological activity as assessed before the administration of r-IFN alpha. Simultaneous kinetic analysis of serum aminotransferases as surrogate markers of hepatocyte integrity revealed half lifes for the release of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from hepatocytes of 4.7 +/- 3.8 and 3.0 +/- 3.5 days, respectively. The half life data for HCV in chronically infected patients are remarkably similar to recently published data on human immunodeficiency virus type 1 (HIV-1) suggesting that both RNA viruses replicate continuously and highly productive in vivo. The turnover rates explain the rapid generation of viral diversity and the opportunity for viral escape phenomena from the host immune surveillance.
Keywords: Alanine Aminotransferase/METABOLISM Antiviral Agents/*PHARMACOLOGY Aspartate Aminotransferase/METABOLISM Chronic Disease Hepatitis C/BLOOD/ENZYMOLOGY/THERAPY/*VIROLOGY Hepatitis C Viruses/GENETICS/*PHYSIOLOGY Human Interferon Alfa, Recombinant/*PHARMACOLOGY Liver/ENZYMOLOGY/PATHOLOGY/VIROLOGY Models, Biological RNA, Viral/METABOLISM Support, Non-U.S. Gov't Viremia Virus Replication JOURNAL ARTICLE

KWDalanineaminotransferase/metabolismantiviralagents/KWDpharmacologyaspartateaminotransferase/metabolismchronicdiseasehepatitisc/blood/enzymology/therapy/KWDvirologyhepatitiscviruses/genetics/KWDphysiologyhumaninterferonalfa,recombinant/KWDpharmacologyliver/enzymology/pathology/virologymodels,biologicalrna,viral/metabolismsupport,non-uKWDsKWDgov'tviremiavirusreplicationjournalarticle
960630
M9660752

Copyright © 1996 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

AEGiS is a 501(c)3, not-for-profit, tax-exempt, educational corporation. AEGiS is made possible through unrestricted funding from Boehringer Ingelheim, Bridgestone/Firestone Charitable Trust, Bristol-Myers Squibb Company, Elton John AIDS Foundation, Gill Foundation, the National Library of Medicine, Quest Diagnostics, Roche and Trimeris, and donations from users like you. Always watch for outdated information. This article first appeared in 1996. This material is designed to support, not replace, the relationship that exists between you and your doctor.

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1996. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .