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One-quarter of Patients Clear Hepatitis Delta with Pegylated Interferon

Treatment with pegylated interferon (Pegasys) -- either alone or in combination with the antiviral drug adefovir (Hepsera) -- led to clearance of hepatitis delta virus (HDV) and improvement in liver enzyme levels, according to a small study published in the January 27, 2011, New England Journal of Medicine. Adefovir alone, however, had no effect on HDV.

Hepatitis D or delta virus is a defective pathogen that can only replicate in the presence of hepatitis B virus (HBV). When the 2 viruses occur together, however, they can cause more severe liver disease than HBV alone. Treatment for hepatitis delta has not been extensively studied and there are currently no approved therapies.

In the present analysis, Heiner Wedemeyer and fellow investigators with the Hep-Net-International Delta Hepatitis Intervention Trial (HIDIT) Study Group investigated the safety and efficacy of 48 weeks of treatment with pegylated interferon, adefovir, or the 2 drugs combined.

This randomized trial included 90 participants with HDV infection. Patients were allocated (1:1:1) to receive either 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 10 mg/day adefovir, the same dose of pegylated interferon plus placebo, or the same dose of adefovir alone for 48 weeks.

Researchers looked at efficacy end-points including normalization of alanine aminotransferase (ALT) liver enzyme levels, clearance of HDV RNA, and decline in hepatitis B surface antigen (HBsAg) levels.

Results

• 2 patients receiving pegylated interferon plus adefovir and 2 receiving pegylated interferon alone achieved ALT normalization at week 48, compared with none in the adefovir monotherapy arm.
• 23% of patients taking pegylated interferon plus adefovir and 24% taking pegylated interferon alone achieved undetectable HDV viral load by week 48, again compared with none taking adefovir alone.
• 28% of patients receiving pegylated interferon either alone or in combination with adefovir experienced sustained virological response, or undetectable HDV RNA 24 weeks after completion treatment, compared with none taking adefovir alone.
• 10 people in the pegylated interferon plus adefovir arm and 2 in the pegylated interferon monotherapy group saw a decline in HBsAg levels of more than 1 log IU/mL from baseline to week 48, again with no responders in the adefovir monotherapy group.

Based on these findings, the study authors concluded, "Treatment with [pegylated interferon] alfa-2a for 48 weeks, with or without adefovir, resulted in sustained HDV RNA clearance in about one quarter of patients with HDV infection."

While adding adefovir to pegylated interferon did not increase the rate of ALT normalization or HDV viral load clearance, it did appear to improve the likelihood of HBsAg decline.

Investigator affiliations: Hannover Medical School, Hannover, Germany; Heinrich Heine University, Düsseldorf, Germany; Johann Wolfgang Goethe University, Frankfurt, Germany; Robert Koch Institute, Berlin, Germany; University Köln, Cologne, Germany; University of Ankara Medical School, Ankara, Turkey; Ufuk University Medical School, Ankara, Turkey; Memorial Hospital Istanbul, Istanbul, Turkey; University of Uludag Medical School, Bursa, Turkey; University Larissa, Larissa, Greece.

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Reference

H Wedemeyer, C Yurdaydin, GN Dalekos, and others (HIDIT Study Group). Peginterferon plus Adefovir versus Either Drug Alone for Hepatitis Delta. New England Journal of Medicine 364(4): 322-331 (Abstract). January 27, 2011