Clinical

Ribavirin's antiviral effect aids interferon in hepatitis C therapy

Last Updated: 2004-03-19 16:03:37 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In patients with chronic hepatitis C, ribavirin improves the effectiveness of interferon alpha treatment. The mechanism that underlies the combined effect of the two drugs is unclear, however.

In the March issue of Gastroenterology, an international team led by Dr. Jean-Michel Pawlotsky of Hopital Henri Mondor in Paris, France, sheds some light on this mechanism with the results of its analysis of viral kinetics and ribavirin pharmacokinetics in patients with chronic hepatitis C.

Thirty-eight patients received either ribavirin or interferon monotherapy, or interferon and ribavirin in combination. Seven patients served as controls.

Of the 7 patients who received ribavirin alone, 4 had "a significant, moderate, early and transient viral load decrease" at days 2 and 3, according to the researchers. This effect was associated with longer ribavirin clearance half-lives and higher serum concentrations.

In the 8 patients treated with the standard 3-times-per-week interferon injections plus daily ribavirin, the antiviral effect of ribavirin partly reduced the viral load rebound that preceded the second injection. "The magnitude of the rebound was inversely related to ribavirin concentrations," the investigators point out.

After the viral load rebound, patients receiving the standard interferon regimen in combination with ribavirin had "a slow, but significant, second slope of viral decrease and cleared HCV RNA." Patients on ribavirin monotherapy, however, did not experience a second decline in either viral level or HCV RNA clearance.

The authors concede that the mechanisms underlying their observations "remain hypothetical." They conclude that ribavirin's transient antiviral effect "helps explain the better initial and end-of-treatment response when ribavirin is added to interferon alpha."

Gastroenterology 2004;126:703-714.