Ahn Sang-Hoon, Kweon Young-Oh, Paik Seung-Woon, Sohn Joo-Hyun, Lee Kwan-Sik, Kim Dong Joon, Piratvisuth Teerha, Yuen Man Fung, Chutaputti Anuchit, Chao You-Chen, Trylesinski Aldo, Avila Claudio
Department of Internal Medicine, Yonsei University College of Medicine, 250 Seongsanno, Seoul, South Korea.
The Kyungpook National University Hospital, Daegu, Korea.
Hepatol Int. 2012 Oct;6(4):696-706. doi: 10.1007/s12072-011-9314-7. Epub 2011 Oct 12.
Lamivudine (LAM) resistance is common on lamivudine monotherapy for chronic hepatitis B. This study examined the safety and efficacy of telbivudine (LDT) given with adefovir (ADV) versus ADV monotherapy in patients with chronic, lamivudine-resistant HBV infection.
An open-label, 96 week study with planned recruitment of 150 HBeAg-positive, lamivudine-experienced Asian patients with a confirmed YMDD resistance mutation, randomized 1:1 to receive ADV alone or with LDT. The study was terminated early due to difficulty in enrolling monotherapy patients. At termination, 42 patients had received study medication for 8-61 weeks. Due to incomplete enrolment, summary statistics only were prepared, without significance testing.
A total of 42 patients underwent rescue therapy (switch to ADV or LDT + ADV; n = 21 per group). Median treatment duration was 48 weeks in both groups. HBV DNA changes from baseline were greater in the LDT + ADV arm at all time points (Week 48: -7.4 log10 vs. -4.9 log10 copies/ml), and serum DNA was undetectable (<300 copies/mL) at week 48 in 38.5% (5/13) on LDT + ADV versus 0% (0/9) on ADV monotherapy Two patients (9.6%) on ADV monotherapy experienced virologic breakthrough without evidence of ADV resistance, but none on LDT + ADV; and no confirmed ADV resistance was observed in any on-treatment sample. HBeAg loss occurred in three patients on LDT + ADV and one patient on ADV monotherapy through week 48. Safety profiles were similar between the arms.
LDT + ADV combination treatment showed better outcomes against lamivudine resistant HBV than ADV alone, with a similar safety profile.
在慢性乙型肝炎的拉米夫定单药治疗中，拉米夫定耐药很常见。本研究考察了替比夫定（LDT）联合阿德福韦（ADV）与阿德福韦单药治疗对慢性拉米夫定耐药HBV感染患者的安全性和疗效。
一项开放标签、为期96周的研究，计划招募150例有拉米夫定治疗史、HBeAg阳性、确诊YMDD耐药突变的亚洲患者，按1:1随机分组，分别接受单用阿德福韦或阿德福韦联合替比夫定治疗。由于单药治疗患者入组困难，研究提前终止。终止时，42例患者接受研究药物治疗8 - 61周。因入组不完全，仅进行了汇总统计，未进行显著性检验。
共有42例患者接受挽救治疗（换用阿德福韦或替比夫定 + 阿德福韦；每组21例）。两组的中位治疗持续时间均为48周。在所有时间点，替比夫定 + 阿德福韦组的HBV DNA相对于基线的变化均更大（第48周：-7.4 log10对-4.9 log10拷贝/ml），在第48周时，替比夫定 + 阿德福韦组有38.5%（5/13）的患者血清DNA不可测（<300拷贝/mL），而阿德福韦单药治疗组为0%（0/9）。阿德福韦单药治疗组有2例患者（9.6%）发生病毒学突破，且无阿德福韦耐药证据，但替比夫定 + 阿德福韦组无此情况；在任何治疗样本中均未观察到确诊的阿德福韦耐药。至第48周，替比夫定 + 阿德福韦组有3例患者发生HBeAg血清学转换，阿德福韦单药治疗组有1例患者发生HBeAg血清学转换。两组的安全性概况相似。
与单用阿德福韦相比，替比夫定 + 阿德福韦联合治疗对拉米夫定耐药HBV的疗效更佳，且安全性概况相似。
