Ooga Hiromi, Suzuki Fumitaka, Tsubota Akihito, Arase Yasuji, Suzuki Yoshiyuki, Akuta Norio, Sezaki Hitomi, Hosaka Tetsuya, Someya Takashi, Kobayashi Masahiro, Saitoh Satoshi, Ikeda Kenji, Kobayashi Mariko, Matsuda Marie, Satoh Junko, Kumada Hiromitsu
Department of Gastroenterology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, 105-8470, Tokyo, Japan.
J Gastroenterol. 2004 Nov;39(11):1078-84. doi: 10.1007/s00535-004-1450-6.
Several clinical trials have suggested that lamivudine therapy is effective in patients with hepatitis B virus (HBV)-related cirrhosis. However, there are few studies of lamivudine therapy in Japanese patients with HBV cirrhosis. The aim of this study was to evaluate the efficacy of lamivudine therapy in Japanese patients with cirrhosis, and to evaluate the clinical course after the emergence of YMDD mutants.
Fifty-four consecutive adult Japanese patients with HBV-related cirrhosis were enrolled and continuously treated with lamivudine, daily for 6-35 months (median, 25 months). Twelve of the 54 patients were hepatitis B envelope antigen (HBeAg)-positive. The clinical courses of 21 of the patients were evaluated using the Child-Pugh-Turcott (CPT) score.
Lamivudine suppressed serum HBV-DNA to undetectable levels (<3.7 LGE/ml) in 77.8% of patients at 12 months and in 61.3% at 24 months. Before the emergence of YMDD mutants, clinical improvement, defined as a decrease in the CPT score of 2 points or more, was apparent in 6 of 21 (29%) patients. No change in CPT score was evident in 14 of 21 patients (67%). YMDD mutants emerged in 19 of 54 (35%) patients. The cumulative emergence rates increased each year. The emergence rate of YMDD mutants in patients with HBV cirrhosis was higher than that in patients with chronic hepatitis. After the emergence of YMDD mutants, 3 of 12 (25%) patients with YMDD mutants showed CPT score increases of 2 points or more.
Lamivudine therapy improved the clinical course in some cirrhotic patients. However, in patients with Child's B and C cirrhosis, the emergence of YMDD mutants sometimes led to deterioration of liver function.
多项临床试验表明，拉米夫定治疗对于乙型肝炎病毒（HBV）相关肝硬化患者有效。然而，针对日本HBV肝硬化患者的拉米夫定治疗研究较少。本研究旨在评估拉米夫定治疗日本肝硬化患者的疗效，并评估YMDD突变体出现后的临床病程。
连续纳入54例成年日本HBV相关肝硬化患者，接受拉米夫定持续治疗，每日一次，疗程6 - 35个月（中位数为25个月）。54例患者中有12例乙型肝炎e抗原（HBeAg）阳性。使用Child-Pugh-Turcott（CPT）评分评估21例患者的临床病程。
拉米夫定在12个月时使77.8%的患者血清HBV-DNA降至不可检测水平（<3.7 LGE/ml），24个月时为61.3%。在YMDD突变体出现之前，21例患者中有6例（29%）临床改善，定义为CPT评分降低2分或更多。21例患者中有14例（67%）CPT评分无明显变化。54例患者中有19例（35%）出现YMDD突变体。累积出现率逐年增加。HBV肝硬化患者中YMDD突变体的出现率高于慢性肝炎患者。YMDD突变体出现后，12例YMDD突变体患者中有3例（25%）CPT评分增加2分或更多。
拉米夫定治疗改善了部分肝硬化患者的临床病程。然而，在Child's B级和C级肝硬化患者中，YMDD突变体的出现有时会导致肝功能恶化。
