Department of Gastroenterology and Hepatology, National University Health System, Singapore.
J Med Virol. 2013 Jan;85(1):26-33. doi: 10.1002/jmv.23392. Epub 2012 Sep 28.
Entecavir switch is one of the treatment options for lamivudine-resistant hepatitis B (HBV) patients in Asia. This study examined the outcome of patients with different baseline resistance genotypes in a cohort study. In this study, 14 patients with chronic HBV were treated with entecavir 1 mg/day for 5 years. Enrolment criteria include: documented lamivudine resistant mutations, treatment with adefovir 10 mg/day for at least 24 weeks, and Child-Pugh score <7. Most had previous failed adefovir therapy and compensated cirrhosis of the liver. Clinical outcomes, liver biochemistries, and HBV DNA were monitored regularly. Patients with virologic breakthrough were rescued with add-on adefovir. At the end of the treatment period, the mean HBV DNA fell from 5.92 × 10(6) (baseline) to 3.67 × 10(1) IU/ml. The presence of a HBV polymerase rtM204V mutation at the baseline was found to be the major risk factor for adverse outcomes. Compared to the patients with the rtM204I mutant, patients with the rtM204V mutant had increased risk of virologic breakthrough (80% vs. 0%, P = 0.010) requiring add-on adefovir, slower virologic responses (log rank test, P = 0.0011), failure to reach undetectable HBV DNA levels (60% vs. 0%, P = 0.045), and higher risk of entecavir-resistance (60% vs. 0%, P = 0.045). All the patients with rtM204I and rtA181 mutants had undetectable HBV DNA from 18th month. In summary, lamivudine-resistant HBV patients with the rtM204V mutation have the highest risk of developing entecavir resistance, and entecavir monotherapy should be avoided. Those with the rtM204I and rtA181V mutations may have lower risks, but regular surveillance for viral breakthrough is required.
恩替卡韦转换是亚洲拉米夫定耐药乙型肝炎（HBV）患者的治疗选择之一。本研究通过队列研究检查了基线耐药基因型不同的患者的结果。本研究中，14 例慢性 HBV 患者接受恩替卡韦 1mg/天治疗 5 年。入组标准包括：有记录的拉米夫定耐药突变、阿德福韦酯 10mg/天治疗至少 24 周和 Child-Pugh 评分<7。大多数患者之前阿德福韦酯治疗失败并有代偿性肝硬化。定期监测临床结果、肝功能和 HBV DNA。对病毒学突破的患者用加用阿德福韦酯进行挽救。治疗期末，HBV DNA 均值从 5.92×10(6)IU/ml（基线）降至 3.67×10(1)IU/ml。发现基线 HBV 聚合酶 rtM204V 突变的存在是不良结局的主要危险因素。与 rtM204I 突变患者相比，rtM204V 突变患者病毒学突破的风险增加（80%比 0%，P=0.010），需要加用阿德福韦酯，病毒学应答较慢（对数秩检验，P=0.0011），无法达到 HBV DNA 不可检测水平（60%比 0%，P=0.045），恩替卡韦耐药风险增加（60%比 0%，P=0.045）。所有 rtM204I 和 rtA181 突变患者在第 18 个月时 HBV DNA 均不可检测。总之，rtM204V 突变的拉米夫定耐药 HBV 患者发生恩替卡韦耐药的风险最高，应避免恩替卡韦单药治疗。rtM204I 和 rtA181V 突变的患者风险可能较低，但需要定期监测病毒突破。
