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Previous Volume 352:2673-2681 June 30, 2005 Number 26 Next

	Full Text PDF PDA Full Text PowerPoint Slide Set Editorial by Lok, A. S.-F. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited E-mail When Letters Appear PubMed Citation

ABSTRACT

Background Treatment with adefovir dipivoxil for 48 weeks resulted in histologic, virologic, and biochemical improvement in patients with hepatitis B e antigen (HBeAg)–negative chronic hepatitis B. We evaluated the effect of continued therapy as compared with cessation of therapy.

Methods One hundred eighty-five HBeAg-negative patients with chronic hepatitis B were assigned to receive 10 mg of adefovir dipivoxil or placebo once daily for 48 weeks (ratio, 2:1). After week 48, patients receiving adefovir dipivoxil were again randomly assigned either to receive an additional 48 weeks of the drug or to switch to placebo. Patients originally assigned to placebo were switched to adefovir dipivoxil. Patients treated with adefovir dipivoxil during weeks 49 through 96 were subsequently offered continued therapy. The primary end points were changes in hepatitis B virus (HBV) DNA and alanine aminotransferase levels.

Results Treatment with adefovir dipivoxil resulted in a median decrease in serum HBV DNA of 3.47 log copies per milliliter (on a base-10 scale) at 96 weeks and 3.63 log copies per milliliter at 144 weeks. HBV DNA levels were less than 1000 copies per milliliter in 71 percent of patients at week 96 and 79 percent at week 144. In the majority of patients who were switched from adefovir dipivoxil to placebo, the benefit of treatment was lost (median change in HBV DNA levels from baseline, –1.09 log copies per milliliter; only 8 percent of patients had levels below 1000 copies per milliliter at week 96). Side effects during weeks 49 through 144 were similar to those during the initial 48 weeks. Resistance mutations rtN236T and rtA181V were identified in 5.9 percent of patients after 144 weeks.

Conclusions In patients with HBeAg-negative chronic hepatitis B, the benefits achieved from 48 weeks of adefovir dipivoxil were lost when treatment was discontinued. In patients treated for 144 weeks, benefits were maintained, with infrequent emergence of viral resistance.

Source Information

From the Department of Medicine and Hepatology, Henry Dunant Hospital (S.J.H.), and Western Attica General Hospital (N.C.T.) — both in Athens; Toronto Western Hospital, University of Toronto, Toronto (E.J.H.); the Department of Internal Medicine, National Chen Kung University Hospital, Tainan, Taiwan (T.-T.C.); Georgios Papanikolaou Hospital, Thessaloniki, Greece (G.K.); Azienda Ospedaliera San Giovanni Battista, Turin, Italy (M.R.); Service d'Hepatologie, INSERM Unité 481; Centre de Recherche Claude Bernard sur les Hepatites Virales, Hôpital Beaujon, Clichy, France (P.M.); the Division of Gastroenterology, National University Hospital, Singapore (S.G.L.); the Armed Forces Institute of Pathology, Washington, D.C. (Z.G.); and Gilead Sciences, Foster City, Calif. (J.M., S.A., S.X., G.C., C.L.B.).

Address reprint requests to Dr. Hadziyannis at the Department of Medicine, Henry Dunant Hospital, 107 Mesogion Ave., Athens 11526, Greece, or at hadziyannis{at}ath.forthnet.gr.

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