Lee Hyo-Suk, Chung Young-Hwa, Lee Kwansik, Byun Kwan Soo, Paik Seung Woon, Han Joon-Yeol, Yoo Kwon, Yoo Hee-Won, Lee Jin Heon, Yoo Byung Chul
Seoul National University Hospital, South Korea.
Hepatology. 2006 May;43(5):982-8. doi: 10.1002/hep.21166.
Clevudine is a nucleoside analog with an unnatural beta-L configuration. In a phase I/II clinical trial, once daily doses ranging from 10 to 200 mg for 28 days were well tolerated, and produced significant antiviral activity. The present study was conducted to assess the degree and durability of the antiviral response to 12 weeks of clevudine treatment, and to investigate its safety and tolerability. A total of 98 patients with HBeAg-positive chronic hepatitis B were randomized to placebo (n=32), 30-mg clevudine (n=32), and 50-mg clevudine (n=34) groups. Patients were followed up after 12 weeks of treatment for a further 24 weeks off-therapy. Median serum hepatitis B virus DNA reductions from baseline at week 12 were 0.20, 4.49, and 4.45 log10 copies/mL in the placebo, 30-mg clevudine, and 50-mg clevudine groups, respectively (P < .0001). Posttreatment antiviral activities were sustained, with 3.32 and 2.99 log10 reductions at week 12 off-therapy and 2.28 and 1.40 log10 reductions at week 24 off-therapies in the 30- and 50-mg clevudine groups, respectively. Median serum alanine aminotransferase (ALT) levels decreased markedly from baseline during clevudine treatment and were maintained below the upper limit of normal throughout the 24 weeks off-therapy in the two clevudine-treated groups. The incidences of adverse events and treatment-emergent grade 3 or 4 laboratory abnormalities were similar for the three groups. In conclusion, clevudine showed potent antiviral activity during therapy and induced a sustained posttreatment antiviral effect for 6 months after a 12-week treatment period, and this was associated with a sustained normalization of ALT levels.
克来夫定是一种具有非天然β-L构型的核苷类似物。在一项I/II期临床试验中，每日一次服用10至200毫克，持续28天，耐受性良好，并产生了显著的抗病毒活性。本研究旨在评估克来夫定治疗12周后抗病毒反应的程度和持久性，并调查其安全性和耐受性。总共98例HBeAg阳性慢性乙型肝炎患者被随机分为安慰剂组（n = 32）、30毫克克来夫定组（n = 32）和50毫克克来夫定组（n = 34）。治疗12周后对患者进行随访，停药后再随访24周。安慰剂组、30毫克克来夫定组和50毫克克来夫定组在第12周时血清乙肝病毒DNA较基线水平的中位数下降分别为0.20、4.49和4.45 log10拷贝/毫升（P <.0001）。治疗后的抗病毒活性得以维持，30毫克和50毫克克来夫定组在停药第12周时分别下降3.32和2.99 log10，在停药第24周时分别下降2.28和1.40 log10。在两个克来夫定治疗组中，克来夫定治疗期间血清丙氨酸氨基转移酶（ALT）水平较基线明显下降，并在停药后的24周内一直维持在正常上限以下。三组的不良事件发生率和治疗中出现的3级或4级实验室异常情况相似。总之，克来夫定在治疗期间显示出强大的抗病毒活性，并在12周治疗期后诱导了持续6个月的治疗后抗病毒效果，这与ALT水平持续正常化有关。
