Early Treatment of Acute Hepatitis C with Pegylated Interferon Monotherapy Produces Better Results than Delayed Combination Therapy

By Liz Highleyman

Acute hepatitis C virus (HCV) infection -- within the first 6 months -- is much easier to treat with interferon-based therapy than chronic infection, but the optimal time for starting therapy, length of treatment, and need for ribavirin are not clearly established.

In a late-breaker presentation at the 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009) last month in Copenhagen, K. Deterding and colleagues with the HEP-NET Acute HCV Study Group described findings from a randomized trial of early versus delayed treatment of acute hepatitis C.

ACUTE HEPATITIS C

Early treatment of acute hepatitis C with interferon monotherapy is highly effective, producing sustained virological response (SVR) rates of 85% or higher, the investigators noted as background. An alternative strategy might be to delay treatment for 3 months, and only treat those patients who did not spontaneously clear the virus during that time.

The HEP-NET Acute HCV-III study was a prospective trial of patients with symptomatic or asymptomatic acute hepatitis C. Eligible individuals were either HCV antibody positive, had elevated ALT (> 10 x upper limit of normal), or were exposed to HCV within the past 4 months. None had hepatitis A, hepatitis B, or HIV coinfection.

A total of 108 participants at 72 centers in Germany enrolled between 2004 and 2008. A majority (60%) were men, the mean age was 40 years, about half had HCV genotype 1, and about 60% had jaundice (icterus). The present efficacy analysis included 89 patents; the other 19 dropped out for various reasons after randomization.

Participants were randomly assigned to receive either immediate treatment with pegylated interferon alfa-2b (PegIntron) monotherapy for 6 months (n = 52), or else delayed treatment with pegylated interferon alfa-2b plus ribavirin for 6 months starting 12 weeks after randomization in patients who remained HCV RNA positive (n = 20). All asymptomatic patients received early treatment with pegylated interferon monotherapy.

Results

In an intent-to-treat (ITT) analysis, the SVR rate was 78% for symptomatic patients in the immediate treatment arm, compared with 54% in the delayed treatment arm (P = 0.034).

Among symptomatic patients in the immediate treatment arm who achieved good adherence -- defined as taking 80% of prescribed therapy -- the SVR rate was 88%.

22% of symptomatic patients (8 of 37) randomized to the delayed treatment arm experienced spontaneous sustained HCV clearance.

The lower ITT SVR rate in the delayed treatment arm was mainly attributable to the high drop-out rate (16 of 37 patients) during the initial 12-week observation period prior to therapy.

When considering only adherent patients who remained in the study, delayed treatment with pegylated interferon plus ribavirin was comparably effective, with an SVR rate of 100% (12 of 12 patients).

Among the asymptomatic participants, the SVR rates were 69% in an ITT analysis and 88% among adherent patients.

Conclusion

"This so far largest prospective and the first randomized European trial on acute hepatitis C confirmed that early immediate treatment with [pegylated interferon alfa-2b] is highly effective in both symptomatic and asymptomatic patients," the investigators concluded.

"Delayed [pegylated interferon alfa-2b] plus ribavirin treatment resulted in lower overall response rates in this real-life treatment setting," they added, "however, if adherence can be assured this strategy seems to be of similar efficacy in symptomatic patients."

Hannover Medical School, HEP-NET: German Network of Competence on Viral Hepatitis, Hannover, Germany; Ludwig-Maximillians-University, Munich, Germany; University of Leipzig, Hannover, Germany; University Hamburg-Eppendorf, Hamburg, Germany; Johannes-Gutenberg University Mainz, Mainz, Germany; University of Bonn, Bonn, Germany; University of Schleswig-Holstein, Campus Kiel, Kiel, Germany; Charité Berlin Campus Virchow-Klinikum, Berlin, Germany.

5/05/09

Reference
K Deterding, N Gruner, J Wiegand, and others. Early versus delayed treatment of acute hepatitis C: the German HEP-NET Acute HCV-III study -- a randomized controlled trial. 44th Annual Meeting of the European Association for the Study of the Liver (EASL 2009). Copenhagen, Denmark. April 22-26, 2009. Abstract 1047.

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