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Can Some Genotype 1 Chronic Hepatitis C Patients Benefit from Shorter Interferon-based Treatment?

Carefully selected genotype 1 chronic hepatitis C patients who experience rapid virological response (RVR) by week 4 of treatment with pegylated interferon plus ribavirin may be able to achieve sustained virological response (SVR) with 24 instead of 48 weeks of therapy, according to a meta-analysis reported in the January 2010 Journal of Hepatology. However, the researchers cautioned, overall sustained response rates are significantly lower with shorter treatment, and this strategy should only be considered for individuals with low pre-treatment HCV viral load and an undetectable level at week 4.

Current standard-of-care therapy for chronic hepatitis C consists of a combination of pegylated interferon alpha (Pegasys or PegIntron) plus weight-adjusted ribavirin for 48 weeks for people with hard-to-treat HCV genotypes 1 or 4, and for 24 weeks (possibly with fixed-dose ribavirin) for those with genotypes 2 or 3.

But interferon and ribavirin can cause difficult side effects, leading numerous research teams to explore whether a shorter duration of therapy might be effective for some patients.

Christophe Moreno from Université Libre de Bruxelles in Belgium and colleaguesperformed a meta-analysis of previous randomized controlled trials comparing pegylated interferon/ribavirin treatment for the standard 48 weeks versus less than 48 weeks in patients with HCV genotype 1 who experience rapid viral decline soon after starting therapy.

Results

• 7 studies were identified for inclusion in the analysis, including a total of 807 genotype 1 rapid responders.
• Sustained virological response 24 weeks after completing therapy was significantly less frequent with shorter treatment durations compared with the standard 48 weeks.
• The mean difference in SVR rate for short duration compared with standard duration treatment was -13.6% (P = 0.004).
• This difference was in part attributable to a higher relapse rate among patients treated for a short duration (mean difference 9.9%; P < 0.001).
• In a sensitivity analysis restricted to studies that used only weight-adjusted ribavirin, shorter treatment duration remained less effective than 48 weeks.
• However, in subgroup of patients with low baseline viral load (< 400,000 IU/mL) and undetectable HCV RNA at week 4, there was no significant difference in SVR rates between 24 and 48 weeks of treatment (mean difference -3.10%).

"In HCV-1 patients with a rapid virological response, 24 weeks of combination therapy with [pegylated interferon alpha] and ribavirin should be considered only in subjects with low baseline viral load," the study authors concluded.

However, they continued, "the optimal cut-off defining low baseline viral load and the impact of the presence of other factors capable of altering treatment response remain subject to debate."

Besides high baseline viral load, other factors that have been shown to predict poorer treatment response include presence of liver cirrhosis, insulin resistance, and HIV coinfection. Shorter duration treatment therefore may be particularly risky for such patients.

Department of Gastroenterology and Hepatopancreatology, Hôpital Erasme, Université Libre de Bruxelles, Bruxelles, Belgium; Service d’Hepatologie, Hôpital Claude Huriez, Lille, France; Service d’Hépato-Gastroentérologie, Hôpital de Jolimont, Haine-Saint-Paul, Belgium; National Reference Centre for Viral Hepatitis B, C and delta, Department of Virology & INSERM U955, Hôpital Henri Mondor, Créteil, France; INSERM U795, Lille, France.

2/16/10

Reference

C Moreno, P Deltenre, JM Pawlotsky, and others. Shortened treatment duration in treatment-naive genotype 1 HCV patients with rapid virological response: A meta-analysis. Journal of Hepatology 52(1): 25-31 (Abstract). January 2010.