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Efficacy and safety of entecavir in lamivudine‐refractory patients with chronic hepatitis B: Randomized controlled trial in Japanese patients
Author(s) -
Suzuki Fumitaka,
Toyoda Joji,
Katano Yoshiaki,
Sata Michio,
Moriyama Mitsuhiko,
Imazeki Fumio,
Kage Masayoshi,
Seriu Taku,
Omata Masao,
Kumada Hiromitsu
Publication year - 2008
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/j.1440-1746.2008.05455.x
Subject(s) - entecavir , lamivudine , medicine , gastroenterology , refractory (planetary science) , chronic hepatitis , hepatitis b , hepatitis b virus , dosing , adefovir , virology , virus , biology , astrobiology
Background and Aim: Entecavir is a potent inhibitor of both wild‐type and lamivudine‐resistant hepatitis B virus (HBV) with proven clinical efficacy. We conducted a randomized, double‐blind, multicenter study in Japan (ETV‐052) evaluating the efficacy and safety of two doses of entecavir in adult patients with lamivudine‐refractory chronic hepatitis B infection. Methods: Eighty‐four patients with chronic hepatitis B who were refractory to lamivudine therapy were switched from lamivudine to daily oral doses of 0.5 mg entecavir (41 patients) or 1 mg entecavir (43 patients) for 52 weeks. Results: The proportions of patients achieving the primary end‐point (≥2 log 10 reduction in HBV‐DNA from baseline by polymerase chain reaction assay or undetectable HBV‐DNA levels [<400 copies/mL] at week 48) were 90% and 93% for entecavir 0.5 mg and 1 mg, respectively, with 33% of patients in each dosing group achieving <400 copies/mL. The mean reduction in HBV‐DNA from baseline was 3.58 and 3.75 log 10 copies/mL for entecavir 0.5 mg and 1 mg, respectively. High proportions of patients achieved alanine aminotransferase normalization at week 48 (0.5 mg 86%, 1 mg 78%). Histological improvement was observed in most patients (0.5 mg 52%, 1 mg 60%). Virological breakthrough (increase in HBV‐DNA of ≥1 log 10 copies/mL from nadir) was observed in one patient but was not associated with selection of entecavir‐associated resistance substitutions. Entecavir was well tolerated, with no patients discontinuing study drug due to adverse events. Conclusions: These findings indicate that entecavir is safe and effective for the treatment of Japanese adults with lamivudine‐refractory chronic hepatitis B.