EFFECT OF RIBAVIRIN ON VIRUS LOAD AND QUASI-SPECIES DISTRIBUTION IN PATIENTS INFECTED WITH HEPATITIS-C VIRUS

Background/Aims: The combination of ribavirin and interferon alfa has potent synergistic effects in the treatment of chronic hepatitis C. Th e antiviral mechanism of ribavirin is unknown. We investigated whether a transient initial antiviral effect of ribavirin was sufficient to i mprove the response to interferon. Methods: Fifteen HCV-infected patie nts (ten male, five female; mean age 45.4+/-11.0 years) treated with r ibavirin (1000-1200 mg) and 17 untreated patients with chronic hepatit is C (11 male, six female; mean age 45.6+/-9.9 years) were investigate d. All patients were either non-responders to (n=19) or relapsed after (n=13) previous interferon treatment. Serum HCV-RNA concentrations an d HCV quasispecies distribution were serially measured over 4 weeks by quantitative reverse transcription-polymerase chain reaction and sing le-strand conformation polymorphism analysis, respectively. Results: I n six of the 15 patients treated with ribavirin, but in none of the co ntrols, serum alanine aminotransferase levels declined by at least 30% . Pretreatment HCV-RNA levels ranged from 5.0 x 10(5)-5.0 x 10(7) copi es/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 t en and five patients, respectively. In HCV-infected patients without t reatment 7/17 patients had minor and 10/17 no changes in viremia, Poly merase chain reaction amplification of the hypervariable region-1 of H CV was successful in 13/15 treated and in 17/17 untreated patients. Ch anges in HCV quasispecies according to the single-strand conformation polymorphism band pattern occurred in only one patient treated with ri bavirin and in three of the untreated patients. Conclusions: Ribavirin monotherapy has no initial antiviral effect on total hepatitis C vire mia nor on HCV quasispecies, Unlike the rapid emergence of antiviral d rug-resistant strains in HIV-infected patients, no viral escape phenom ena are observed in HCV-infected patients treated with ribavirin.