Abstract
Background/Aims: The combination of ribavirin and interferon alfa has potent synergistic effects in the treatment of chronic hepatitis C. The antiviral mechanism of ribavirin is unknown. We investigated whether a transient initial antiviral effect of ribavirin was sufficient to improve the response to interferon. Methods: Fifteen HCV-infected patients (ten male, five female; mean age 45.4±11.0 years) treated with ribavirin (1000–1200 mg) and 17 untreated patients with chronic hepatitis C (11 male, six female; mean age 45.6±9.9 years) were investigated. All patients were either non-responders to ( n=19) or relapsed after ( n=13) previous interferon treatment. Serum HCV-RNA concentrations and HCV quasispecies distribution were serially measured over 4 weeks by quantitative reverse transcription-polymerase chain reaction and single-strand conformation polymorphism analysis, respectively. Results: In six of the 15 patients treated with ribavirin, but in none of the controls, serum alanine amino-transferase levels declined by at least 30%. Pretreatment HCV-RNA levels ranged from 5.0×10 5-5.0×10 7 copies/ml. After initiation of ribavirin treatment, minor (0.5–1.0 log) or no changes (<0.5 log) in total hepatitis C viremia were observed in ten and five patients, respectively. In HCV-infected patients without treatment 7 17 patients had minor and 10 17 no changes in viremia. Polymerase chain reaction amplification of the hypervariable region-1 of HCV was successful in 13 15 treated and in 17 17 untreated patients. Changes in HCV quasispecies according to the single-strand conformation polymorphism band pattern occurred in only one patient treated with ribavirin and in three of the untreated patients. Conclusions: Ribavirin monotherapy has no initial antiviral effect on total hepatitis C viremia nor on HCV quasispecies. Unlike the rapid emergence of antiviral drug-resistant strains in HIV-infected patients, no viral escape phenomena are observed in HCV-infected patients treated with ribavirin.
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