AASLD 2013重新评估病毒学应答的概念

StephenW

TITLE: Reappraisal of the Concept of Primary Virologic Response Defined by the Current Guidelines for the Management of Chronic Hepatitis B
AUTHORS (FIRST NAME, LAST NAME): Young Joo Yang1, Ju Hyun Shim2, Kang Mo Kim2, Young-Suk Lim2, Han Chu Lee2, Dong Jin . Suh2, 3
Institutional Author(s):
INSTITUTIONS (ALL): 1. Internal Medicine, Asan medical center, University of Ulsan College of Medicine, Seoul, Korea, Republic of.
2. Gastroenterology, Asan medical center, University of Ulsan College of Medicine, Seoul, Korea, Republic of.
3. Internal Medicine, Vievis Namuh Hospital, Seoul, Korea, Republic of.
ABSTRACT BODY: Background & Aims
Given the substantial evidence that early hepatitis B virus (HBV) DNA response after oral antiviral therapy can strongly predict prolonged virologic outcomes, treatment adaptation at an early phase is strongly recommended for chronic hepatitis B (CHB) patients with primary non-response during treatment. The purpose of this study is to assess whether the definition of primary virologic response to guide the CHB treatment algorithm suggested by the AASLD guidelines was optimal for treatment with entecavir, a newer and more potent antiviral agent.
Methods
This retrospective study included 1,262 treatment-naïve CHB patients receiving entecavir (0.5mg/day) monotherapy for over six months: median age 47 years, 63 % Male, 55% HBeAg-positive, and 42% cirrhosis. All patients had an HBV DNA level of at least 2,000 IU/mL at the start of their entecavir treatment. “Primary non-response” was defined as <2 log decrease in the serum HBV DNA level from the baseline after at least six months of therapy, according to the AASLD guidelines. The primary endpoint of this study was the virologic response, evidenced by achieving the serum HBV DNA to an undetectable level (<15 IU/mL) during the study period. The cumulative probability of a virologic response was evaluated and compared between the groups using Kaplan-Meier analysis and the log-rank test.
Results
In our study, the median duration of entecavir therapy was 31 months (range, 6 to 72 months). A total of 19 (1.5%) patients were categorized as primary non-responders. The cumulative rates for achieving a virologic response over time were 68.3%, 88%, 95%, and 95.7%, respectively, at 12, 24, 36, and 48 months, and which were significantly greater than the 29.4%, 64%, 88%, and 88%, respectively, seen in the primary non-responders (P=0.002). At 48 months, the proportion of virologic responders (95.6% vs 100%) and the mean reduction in the serum HBV DNA levels (-5.08 vs. -6.79 log10 IU/mL) were not associated with the presence of a primary response (P=NS for both). Entecavir resistance mutation emerged in 13 of the 36 patients who showed a virologic breakthrough during follow-up, and all of whom were classified as primary responders.
Conclusions
Our data indicate that long-term entecavir therapy leads to the ultimate virologic response in the vast majority of CHB patients, although the time required to achieve a virologic response was later in patients who did not show a primary response at six months. The current concept of primary non-response for early treatment adaptation should be refined on a drug-related basis in this current era of potent antivirals

StephenW

背景及目的
鉴于大量的证据显示，早期乙肝病毒（HBV） DNA的反应口服抗病毒药物治疗后，可以强烈地预测长期的病毒学结果的早期阶段，治疗适应强烈推荐治疗慢性乙型肝炎（ CHB ）患者在治疗过程中主要的非响应。这项研究的目的是评估指导CHB治疗AASLD指南建议的算法主病毒学应答的定义是，一个新的和更有效的抗病毒药物恩替卡韦治疗的最佳。
方法
这项回顾性研究包括1,262治疗初治慢性乙肝患者接受恩替卡韦单药治疗超过六个月（ 0.5mg/day ） ：平均年龄47岁， 63 ％为男性，55％的HBeAg阳性， 42 ％的肝硬化。所有患者有至少2,000 IU / mL的HBV DNA水平在开始他们的恩替卡韦治疗。 “初级无应答”被定义为<2个数量减少，从基线血清HBV DNA水平，至少6个月的治疗后，根据AASLD指南。这项研究的主要终点是病毒学应答，证明了实现血清HBV DNA检测不到的水平（ <15 IU / mL）的研究期间。的病毒学应答的累积概率进行评估和比较各组之间采用Kaplan-Meier分析和log-rank检验。
结果
在我们的研究中，恩替卡韦治疗时间中位数为31个月（ 6〜72个月） 。共19例（1.5％）被归类为原发性非应答。累积随着时间的推移达到病毒学应答率分别为68.3 ％， 88％， 95 ％和95.7 ％ ，分别在12 ， 24， 36 ，和48个月，均显着大于29.4 ％，64％ ， 88％，和88％ ，分别看出，在主要的非反应者（ P = 0.002） 。病毒学反应者的比例（95.6％和100％）和平均血清HBV DNA水平的降低（ -5.08比-6.79 log10的国际单位/毫升）在48个月内，不相关的主响应的存在下（P = NS两个） 。恩替卡韦耐药变异出现在13谁发现了病毒学突破随访期间的36例患者中，所有的人被列为初级急救员。
结论
我们的数据表明，恩替卡韦长期治疗导致的慢性乙肝患者中的绝大多数最终病毒学应答，但所需要的时间，实现了患者在6个月内并没有显示出主要反应在后来的病毒学应答。原发性非响应早期治疗适应目前的概念应提炼毒品有关的基础上，在当前的时代强效抗病毒药物

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