recently published data on human immunodeficiency vi-In about 30% to 40% of patients with chronic hepatitis rus type 1 (HIV-1) suggesting that both RNA viruses rep-C, treatment with recombinant interferon alfa (r-IFNa) licate continuously and highly productive in vivo. The causes a decrease of serum aminotransferases and hepaturnover rates explain the rapid generation of viral dititis C virus (HCV) RNA. The antiviral mechanism of versity and the opportunity for viral escape phenomena interferon alfa (IFNa) in vivo is unknown. From serial from the host immune surveillance. (HEPATOLOGY measurements of serum HCV-RNA concentrations fol-1996;23:366-371.) lowing IFNa induced perturbation of the balance between virus production and clearance, we obtained kinetic information on the pretreatment steady-state of
The hepatitis C virus (HCV) is an enveloped positive-HCV. In patients with chronic hepatitis C responding to stranded RNA virus that preferentially replicates in IFNa, HCV-RNA declined exponentially with a half life hepatocytes. Infection with HCV often progresses to of approximately 2 days. Modeling of the data predicts chronic hepatitis, liver cirrhosis, and possibly, hepatothat in patients with chronic hepatitis C responding to cellular carcinoma. [1][2][3][4] Treatment of chronically infected
IFNa this cytokine predominantly acts as an inhibitor
patients with recombinant interferon alfa (r-IFNa) can of de novo infection of susceptible cells. HCV is released from infected cells with a mean half life of 2.7 { 1.3 days, achieve initial (and less frequently sustained) clearwhereas the clearance rate from serum is faster (mean ance of HCV from serum. [5][6][7] Interferon alfa (IFNa) inhalf life, 0.7 { 0.4 days). The minimum virus production duces several direct and indirect antiviral mechanisms and clearance per day in patients with chronic hepatitis such as intracellular viral RNA degradation, inhibition C was calculated to be 6.7 1 10 10 virions/d (range, 0.2 to of viral RNA translation, activation of key components 43.8 1 10 10 virions/d). These values showed no correlaof the cellular immune system important in viral recogtion with the HCV genotype, aminotransferase levels, or nition, and prevention of viral infection of susceptible the histological activity as assessed before the adminiscells. 8,9 However, the predominant in vivo antiviral tration of r-IFNa. Simultaneous kinetic analysis of semechanism of IFNa in patients with chronic hepatitis rum aminotransferases as surrogate markers of hepato-C is unknown.
cyte integrity revealed half lifes for the release of alanine aminotransferase (ALT) and aspartate amino-
In the present study, we administered r-IFNa to patransferase (AST) from hepatocytes of 4.7 { 3.8 and 3.0 tients chronically infected with HCV to perturb the { 3.5 days, respectively. The half life data for HCV in balance between virus production and clearance. From chronically infected patients are remarkably similar to serial measurements of changes in viremia in patients responding to r-IFNa, we obtained kinetic information on the dynamics of HCV replication in vivo. Modeling Abbreviations: HCV, hepatitis C virus; r-IFNa, recombinant interferon alfa;
of the data was performed to obtain information on the IFNa, interferon alfa; HIV-1, human immunodeficiency virus type 1; RT, repredominant antiviral effect of r-IFNa in patients with verse transcription; PCR, polymerase chain reaction; ALT, alanine aminochronic hepatitis C.