title: Combination therapy of lamivudine and adefovir in Japanese patients with chronic hepatitis B.
abstract: This study aimed to clarify the long-term efficacy of the lamivudine treatment in Japanese patients with chronic hepatitis B either with or without lamivudine resistance or with or without adefovir add-on treatment.
  
  
  
  We followed 110 patients who received lamivudine for more than 12 months, including 67 hepatitis B e antigen (HBeAg)-positive and 43 HBeAg-negative patients.
  
  
  
  The median follow-up after the onset of lamivudine was 48 (range = 12-86) months. In all the patients with or without lamivudine resistance, the level of alanine aminotransferase (ALT) normalization decreased from 70.0% at 1 year to 36.4% at 5 years and the loss of serum HBV DNA level decreased from 72.7% at 1 year to 31.8% at 5 years. Sixty patients (54.6%) developed a lamivudine-resistant mutation, and this occurrence was more frequently observed in those who were HBeAg-positive (P < 0.01), those with a low level of ALT (P < 0.05), and those with a high level of serum HBV DNA (P < 0.01). Thirty-six of 60 patients received adefovir in addition to lamivudine to treat breakthrough hepatitis. A Cox proportional hazards model analysis revealed the level of baseline HBV DNA to be the best predictive factor for the virus recrudescence (risk ratio = 0.466, 95% confidence interval [CI]: 0.246-0.842, P = 0.011) and the breakthrough hepatitis (risk ratio = 0.444, 95% CI: 0.218-0.879, P = 0.019). We carefully monitored the efficacy of this treatment both in patients who received adefovir and in those who did not since the beginning of the lamivudine treatment. The normalization level of ALT was 61.4% at 5 years and the loss of serum HBV DNA was 61.4% at 5 years since lamivudine was started. A histologic improvement was observed in patients with ALT levels less than two times the upper limit of normal at the time of a second liver biopsy.
  
  
  
  Although the efficacy of lamivudine is limited because of breakthrough hepatitis, adefovir was used as a salvage treatment of patients with lamivudine-resistant chronic hepatitis B. In addition, lamivudine was used for the treatment of Japanese patients with chronic hepatitis B with or without lamivudine resistance, and was found to be useful regarding the long-term virologic and biochemical responses.
authors: The Department of Gastroenterology and Hepatology, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan, shakado@cis.fukuoka-u.ac.jp.
authors: Satoshi
authors: S
authors: Shakado
authors: Hiroshi
authors: H
authors: Watanabe
authors: Takashi
authors: T
authors: Tanaka
authors: Daisuke
authors: D
authors: Morihara
authors: Shinya
authors: S
authors: Nishizawa
authors: Shinjiro
authors: S
authors: Inomata
authors: Syuichi
authors: S
authors: Ueda
authors: Teruo
authors: T
authors: Matsumoto
authors: Akira
authors: A
authors: Anan
authors: Yasuaki
authors: Y
authors: Takeyama
authors: Makoto
authors: M
authors: Irie
authors: Kaoru
authors: K
authors: Iwata
authors: Tetsuro
authors: T
authors: Sohda
authors: Shotaro
authors: S
authors: Sakisaka