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Previous Volume 351:1206-1217 September 16, 2004 Number 12 Next

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ABSTRACT

Background Available treatments for hepatitis B e antigen (HBeAg)–negative chronic hepatitis B are associated with poor sustained responses. As a result, nucleoside and nucleotide analogues are typically continued indefinitely, a strategy associated with the risk of resistance and unknown long-term safety implications.

Methods We compared the efficacy and safety of peginterferon alfa-2a (180 µg once weekly) plus placebo, peginterferon alfa-2a plus lamivudine (100 mg daily), and lamivudine alone in 177, 179, and 181 patients with HBeAg-negative chronic hepatitis B, respectively. Patients were treated for 48 weeks and followed for an additional 24 weeks.

Results After 24 weeks of follow-up, the percentage of patients with normalization of alanine aminotransferase levels or hepatitis B virus (HBV) DNA levels below 20,000 copies per milliliter was significantly higher with peginterferon alfa-2a monotherapy (59 percent and 43 percent, respectively) and peginterferon alfa-2a plus lamivudine (60 percent and 44 percent) than with lamivudine monotherapy (44 percent, P=0.004 and P=0.003, respectively; and 29 percent, P=0.007 and P=0.003, respectively). Rates of sustained suppression of HBV DNA to below 400 copies per milliliter were 19 percent with peginterferon alfa-2a monotherapy, 20 percent with combination therapy, and 7 percent with lamivudine alone (P<0.001 for both comparisons with lamivudine alone). Loss of hepatitis B surface antigen occurred in 12 patients in the peginterferon groups, as compared with 0 patients in the group given lamivudine alone. Adverse events, including pyrexia, fatigue, myalgia, and headache, were less frequent with lamivudine monotherapy than with peginterferon alfa-2a monotherapy or combination therapy.

Conclusions Patients with HBeAg-negative chronic hepatitis B had significantly higher rates of response, sustained for 24 weeks after the cessation of therapy, with peginterferon alfa-2a than with lamivudine. The addition of lamivudine to peginterferon alfa-2a did not improve post-therapy response rates.

Source Information

From the Service d'Hépatologie, INSERM Unité 481 and Centre de Recherches Claude Bernard sur les Hépatites Virales, Hôpital Beaujon, Clichy, France (P.M.); Queen Mary Hospital, University of Hong Kong, Hong Kong, China (G.K.K.L.); Istituto di Ricovero e Cura a Carratere Scientifico, Ospedale Maggiore di Milano Policlinico, Milan, Italy (F.B.); the Division of Clinical Medicine I, University of Cagliari, Cagliari, Italy (P.F.); the Department of Medicine and Hepatology, Henry Dunant Hospital, Athens (S.H.); the Digestive Disease Department, Beijing You An Hospital, Beijing (R.J.); the Department of Infectious Diseases, Ruijin Hospital, Shanghai, China (Z.-M.L.); Songklanakarin Hospital, Songkla, Thailand (T.P.); Papageorgiou General Hospital, Pathology Clinic, Thessalonika, Greece (G.G.); University of Ankara, Faculty of Medicine, Ankara, Turkey (C.Y.); Hospital General Universitario de Valencia, Valencia, Spain (M.D.); University of Uludag, Faculty of Medicine, Bursa, Turkey (S.G.); National Taiwan University Hospital, Internal Medicine, Taipei, Taiwan (M.-Y.L.); Roche, Dee Why, Australia (P.B.); and Roche, Welwyn, United Kingdom (N.P.).

Address reprint requests to Dr. Marcellin at the Service d'Hépatologie, INSERM Unité 481 and Centre de Recherches Claude Bernard sur les Hépatites Virales, Hôpital Beaujon, 92110 Clichy, France, or at patrick.marcellin{at}bjn.ap-hop-paris.fr.

Full Text of this Article

Related Letters:

Peginterferon and Lamivudine for Hepatitis B
Assy N. N., Hussein O., Marcellin P., the Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group
Extract | Full Text | PDF  
N Engl J Med 2004; 351:2879, Dec 30, 2004. Correspondence

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