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J Gastroenterol. 2013 Mar;48(3):397-404. doi: 10.1007/s00535-012-0645-5. Epub 2012 Aug 2.

Entecavir and interferon-α sequential therapy in Japanese patients with hepatitis B e antigen-positive chronic hepatitis B.

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Department of Hepatology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, 545-8585, Japan.



The outcomes of sequential therapy with lamivudine followed by interferon have been unsatisfactory in Japanese patients with hepatitis B envelope antigen (HBeAg)-positive chronic hepatitis B. However, the efficacy of sequential therapy with entecavir and interferon remains unclear.


Twenty-four HBeAg-positive patients (23 men and 1 woman; mean age 39 ± 7 years) received entecavir 0.5 mg alone for 36-52 weeks, followed by entecavir plus interferon-α for 4 weeks, and lastly by interferon-α alone for 20 weeks. Twenty-three patients had genotype C infection, and one had genotype A infection.


No entecavir-resistant mutant variants emerged in any patient. Hepatitis flare occurred in three patients during interferon-α treatment after the withdrawal of entecavir, but none had hepatic decompensation. Serum hepatitis B surface antigen levels did not change during or after therapy. Serum hepatitis B core-related antigen levels were significantly decreased at the start (P < 0.0001) and at the end of interferon-α treatment (P < 0.0001), but returned to baseline levels after treatment. Twenty-four weeks after the completion of the sequential therapy, a sustained biochemical, virological, and serological response was achieved in 5 (21 %) patients. The proportion of patients in whom HBeAg was lost during entecavir treatment was significantly higher among those with a sustained response than among those with no response (P = 0.015).


The rate of response to sequential therapy with entecavir and interferon-α in Japanese patients with HBeAg-positive chronic hepatitis B was not higher than the rate in previous studies of lamivudine followed by interferon.

[Indexed for MEDLINE]

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