不同拉米夫定耐药基因型具有相同的恩替卡韦耐药的风险？

StephenW

不同拉米夫定耐药基因型具有相同的恩替卡韦耐药的风险？
J Med Virol. <http://www.ncbi.nlm.nih.gov/pubmed/&gt; 2012 Sep 28. doi: 10.1002/jmv.23392. [Epub ahead of print]

Do different lamivudine-resistant hepatitis B genotypes carry the same risk of entecavir resistance?

Lee GH, Aung MO, Dan YY, Lee YM, Mak B, Low HC, Lim K, Thwin MA, Tan PS, Lim SG.

Source

Department of Gastroenterology and Hepatology, National University Health System, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Abstract

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. J. Med. Virol. © 2012 Wiley Periodicals, Inc.

StephenW

恩替卡韦开关是拉米夫定耐药的乙肝病毒（HBV）在亚洲患者的治疗选择之一。本研究旨在探讨不同的基准电阻基因型患者的队列研究的结果。在这项研究中，14例慢性乙型肝炎治疗用恩替卡韦1毫克/天，为5年。入学标准包括：记录的耐药突变，阿德福韦酯10 mg /日，至少24周的治疗，及Child-Pugh评分<7分。大多数先前失败的的阿德福韦治疗和补偿肝硬化。临床结果，肝biochemistries，HBV DNA进行定期监测。附加阿德福韦病毒学突破的患者获救。在治疗期间，平均HBV DNA下降至5.92×10（6）（基线）3.67×10（1）IU /毫升。在基线的HBV聚合酶rtM204V突变的存在被认为是不良后果的主要危险因素。的rtM204I突变的患者相比，患者的病毒学突破与rtM204V突变的风险增加（80％比10％，P = 0.010）需要附加上阿德福韦，速度较慢的病毒学应答（对数秩检验，P = 0.0011） ，未能达到HBV DNA检测不到的水平（60％对10％，P = 0.045），恩替卡韦电阻和高风险（60％对0％，P = 0.045）。 rtM204I和rtA181突变的患者HBV DNA检测不到18个月。总之，拉米夫定耐药的乙肝患者与rtM204V突变发展中恩替卡韦耐药的危险性最高，恩替卡韦单药治疗，应避免。 rtM204I和rtA181V突变可能具有较低的风险，但需要定期监测病毒的突破。 J.医学。病毒学©2012威利期刊，