Furusyo Norihiro, Takeoka Hiroaki, Toyoda Kazuhiro, Murata Masayuki, Tanabe Yuichi, Kajiwara Eiji, Shimono Junya, Masumoto Akihide, Maruyama Toshihiro, Nomura Hideyuki, Nakamuta Makoto, Takahashi Kazuhiro, Shimoda Shinji, Azuma Koichi, Sakai Hironori, Hayashi Jun
Department of General Medicine, Kyushu University Hospital, Higashi-Ku, Fukuoka 812-8582, Japan.
World J Gastroenterol. 2006 Jan 28;12(4):561-7. doi: 10.3748/wjg.v12.i4.561.
To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B.
In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 (median 21) mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment.
Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL (P<0.0001), HBeAg negativity (P<0.0001), a platelet count of 100 x 10(9)/L or more (P=0.0162) at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment (P=0.0003) to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at >=5 mo. A virological breakthrough was found significantly more often in patients with delayed virological response.
Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.
确定长期使用拉米夫定治疗大量日本慢性乙型肝炎患者的疗效。
在这项回顾性多中心试验中，318例日本慢性乙型肝炎患者每日服用100mg拉米夫定，最长达36（中位数21）个月。病毒学应答定义为血清HBV DNA水平降至低于3.7 log拷贝/mL。病毒学突破定义为血清HBV DNA水平再次出现至治疗期间最低值的10倍以上。
拉米夫定在6个月时使318例患者中的86.8%产生病毒学应答，12个月时使252例患者中的80.2%产生应答，24个月时使133例患者中的69.2%产生应答，36个月时使28例患者中的53.6%产生应答。向前逐步逻辑回归分析显示，基线时HBV DNA水平低于6.8 log拷贝/mL（P<0.0001）、HBeAg阴性（P<0.0001）、血小板计数为100×10⁹/L或更高（P=0.0162），以及治疗开始后3个月时HBV DNA水平较基线水平下降超过3.2 log拷贝/mL（P=0.0003）与病毒学应答显著相关。在产生病毒学应答的患者中，1个月时产生病毒学应答的19例患者中有5.3%出现病毒学突破，3个月时203例患者中有20.7%出现突破，6个月时51例患者中有27.5%出现突破，9个月时12例患者中有33.3%出现突破，≥5个月时3例患者中有100%出现突破。病毒学应答延迟的患者中病毒学突破的发生率明显更高。
拉米夫定治疗可抑制大多数受试日本患者的血清HBV DNA。基线时无HBeAg、无肝硬化且治疗开始后HBV DNA水平很快下降的患者可能有长期疗效。
