Clinical—Liver, Pancreas, and Biliary TractRibavirin Improves Early Responses to Peginterferon Through Improved Interferon Signaling
Section snippets
Materials and Methods
Treatment-naïve patients infected with HCV genotype 1 evaluated at the Clinical Center of the National Institutes of Health were recruited for study participation. For study inclusion, patients had to be at least 18 years of age with chronic HCV infection and a liver biopsy within 2 years of study entry. Patients with hepatitis B or human immunodeficiency virus coinfection were excluded, as were those with other causes of chronic liver disease or comorbidities precluding interferon therapy. The
Results
Baseline characteristics were similar between the 2 groups (Table 1). Two patients, 1 from each group, were excluded from the analysis. One patient who was initially reported to have genotype 1 infection was found to have genotype 6 infection by sequencing of the NS5B region. The second patient suffered a cerebrovascular accident during the 2nd week of therapy and stopped treatment early, precluding viral kinetic calculations.
Discussion
Despite the major contribution that ribavirin provides in improving treatment outcomes in chronic HCV infection, the mechanism by which it acts has been hard to tease apart. The poor understanding of its mechanism of action has made development of ribavirin analogues difficult. A close examination of early viral kinetics, mutagenesis, and cytokine levels during peginterferon therapy with and without ribavirin offers some clues to understanding the action of this important adjunctive agent.
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Conflicts of interest This author discloses the following: Dr Feld reports being a member of the advisory board for Roche Canada and Schering-Plough Canada. The remaining authors disclose no conflicts.
Funding This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases.