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Pegasys for HBV: what is the treatment role?
  Peginterferon Alfa-2a Beats Lamivudine for HBeAg-Positive Chronic HBV
Current therapy for chronic hepatitis B virus (HBV) infection includes interferon and oral agents such as lamivudine, adefovir, and entecavir. In a multinational, randomized, partially blinded, industry-sponsored trial, researchers compared the efficacy of peginterferon alfa-2a alone (180 µg/week with oral placebo), lamivudine alone (100 mg/day), and both drugs in 814 hepatitis B e antigen (HBeAg)-positive patients.
All patients were treated for 48 weeks and followed for an additional 24 weeks. At the end of follow-up, seroconversion rates (loss of HBeAg) were significantly higher with peginterferon monotherapy and combination therapy than with lamivudine monotherapy (32% and 27% vs. 19%). Rates of viral suppression (HBV DNA levels <100,000 copies/mL) were also significantly higher with peginterferon alone and combination therapy compared with lamivudine alone (32% and 34% vs. 22%). Hepatitis B surface antigen (HBsAg) seroconversion occurred significantly more often with peginterferon monotherapy than with lamivudine alone (3% vs. 0%). Furthermore, at the end of the 48-week treatment period, lamivudine resistance was detected in significantly more patients who received lamivudine alone than in patients who received combination therapy (4% vs. 27%).
Comment: Peginterferon alfa-2a alone (now FDA approved) appears to be superior to lamivudine alone in patients with HBeAg-positive chronic hepatitis B infection, resulting in higher rates of HBeAg and HBsAg seroconversion and viral suppression. Although combination therapy did not improve efficacy, it produced less resistance to lamivudine than did lamivudine alone. Additional trials are needed to evaluate longer-term efficacy of peginterferon alfa-2a in patients with HBeAg-positive chronic HBV.
- Atif Zaman, MD, MPH
Published in Journal Watch Gastroenterology August 9, 2005
Lau GKK et al. Peginterferon alfa-2a, lamivudine, and the combination for HBeAg-positive chronic hepatitis B. N Engl J Med 2005 Jun 30; 352:2682-95.
Links to relevant NATAP website articles on HBV therapy:
The Maze of Treatments for Hepatitis B - (06/30/05)
New Perspectives in the Treatment of HBeAg-positive and HBeAg-negative Chronic
Hepatitis B, Pegylated Interferon - (05/25/05)
Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B - (06/30/05)
Peginterferon Alfa-2a, Lamivudine, and the Combination for HBeAg-Positive Chronic Hepatitis B

New England Journal of Medicine June 2005
George K.K. Lau, M.D., Teerha Piratvisuth, M.D., Kang Xian Luo, M.D., Patrick Marcellin, M.D., Satawat Thongsawat, M.D., Graham Cooksley, M.D., Edward Gane, M.D., Michael W. Fried, M.D., Wan Cheng Chow, M.D., Seung Woon Paik, M.D., Wen Yu Chang, M.D., Thomas Berg, M.D., Robert Flisiak, M.D., Philip McCloud, Ph.D., Nigel Pluck, M.D., for the Peginterferon Alfa-2a HBeAg-Positive Chronic Hepatitis B Study Group
Background Current treatments for chronic hepatitis B are suboptimal. In the search for improved therapies, we compared the efficacy and safety of pegylated interferon alfa plus lamivudine, pegylated interferon alfa without lamivudine, and lamivudine alone for the treatment of hepatitis B e antigen (HBeAg)Špositive chronic hepatitis B.
Methods A total of 814 patients with HBeAg-positive chronic hepatitis B received either peginterferon alfa-2a (180 µg once weekly) plus oral placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), or lamivudine alone. The majority of patients in the study were Asian (87 percent). Most patients were infected with hepatitis B virus (HBV) genotype B or C. Patients were treated for 48 weeks and followed for an additional 24 weeks.
Results After 24 weeks of follow-up, significantly more patients who received peginterferon alfa-2a monotherapy or peginterferon alfa-2a plus lamivudine than those who received lamivudine monotherapy had HBeAg seroconversion (32 percent vs. 19 percent [P<0.001] and 27 percent vs. 19 percent [P=0.02], respectively) or HBV DNA levels below 100,000 copies per milliliter (32 percent vs. 22 percent [P=0.01] and 34 percent vs. 22 percent [P=0.003], respectively). Sixteen patients receiving peginterferon alfa-2a (alone or in combination) had hepatitis B surface antigen (HBsAg) seroconversion, as compared with 0 in the group receiving lamivudine alone (P=0.001). The most common adverse events were those known to occur with therapies based on interferon alfa. Serious adverse events occurred in 4 percent, 6 percent, and 2 percent of patients receiving peginterferon alfa-2a monotherapy, combination therapy, and lamivudine monotherapy, respectively. Two patients receiving lamivudine monotherapy had irreversible liver failure after the cessation of treatment - one underwent liver transplantation, and the other died.
Conclusions In patients with HBeAg-positive chronic hepatitis B, peginterferon alfa-2a offers superior efficacy over lamivudine, on the basis of HBeAg seroconversion, HBV DNA suppression, and HBsAg seroconversion.
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