恩替卡韦抑制乙肝病毒是否影响临床的结果?

StephenW

Does HBV Suppression with Entecavir Affect Clinical Outcomes?

Evidence from an ongoing prospective cohort study indicates yes, but only in patients with cirrhosis, and only when virologic response is strong.

Suppression of hepatitis B virus (HBV) with antiviral agents, such as entecavir, has been shown to reduce the risk for hepatocellular carcinoma (HCC) and progression of liver fibrosis. Less clear is whether viral suppression leads to improved clinical outcomes, such as reduction in HCC, decompensation, and death.

To investigate this issue, researchers in Europe prospectively evaluated whether virologic response (HBV DNA level <80 IU/mL) reduced the composite endpoint of hepatic decompensation, HCC, or death in patients taking entecavir for chronic HBV infection. They also examined the efficacy of entecavir by severity of liver disease at baseline and baseline factors associated with disease progression.

The cohort comprised 372 patients (274 without cirrhosis, 89 with compensated cirrhosis. and 9 with decompensated cirrhosis). Median follow-up was 20 months. Results are as follows:

    The cumulative probability of achieving virologic response was 68% at week 48 and 93% at week 144.
    Virologic response was not influenced by baseline disease severity.
    Thirteen patients developed a clinical event (decompensation, 6; HCC, 3; death, 7).
    The probability of developing a clinical event was higher in patients with cirrhosis (hazard ratio, 15.4; 95% confidence interval, 3.4–69.5).
    Virologic response was associated with reduced risk for developing a clinical event in patients with cirrhosis (HR, 0.22; P=0.04).
    Using a threshold of HBV DNA <2000 IU/mL, virologic response was no longer associated with a reduced risk for developing a clinical event (HR, 0.20; P=0.10).

Comment: This large cohort study demonstrates that entecavir not only effectively suppresses hepatitis B virus in patients at all levels of liver disease severity but, more importantly, improves clinical outcomes in those with cirrhosis. I suspect that the lack of clinical benefit seen in patients without cirrhosis was because of the relatively short follow-up period. As this cohort study accrues more follow-up time, I expect that the clinical benefits of virologic response will be evident across all levels of disease severity. This study also highlights that virologic response needs to be vigorous to reap the benefits of treatment.

— Atif Zaman, MD, MPH

Published in Journal Watch Gastroenterology April 19, 2013
Citation(s):

Zoutendijk R et al. Virological response to entecavir is associated with a better clinical outcome in chronic hepatitis B patients with cirrhosis. Gut 2013 May; 62:760. (http://dx.doi.org/10.1136/gutjnl-2012-302024)

StephenW

从正在进行的前瞻性队列研究的证据表明肯定的，但只有在肝硬化患者中，只有当病毒学应答强。

抑制B型肝炎病毒（HBV）具有抗病毒的药物，如恩替卡韦，已被证明为肝细胞癌（HCC）和肝纤维化的进展，以减少风险。不太清楚的是抑制病毒是否导致改善临床结果，如减少肝癌，失代偿和死亡。

为了研究这个问题，研究人员在欧洲前瞻性评估是否病毒学应答（HBV DNA水平<80 IU / mL）的降低肝功能失代偿，肝癌，或服用恩替卡韦治疗慢性HBV感染患者死亡的复合终点。他们还研究了肝病的严重程度与疾病进展的基准和基准因素恩替卡韦的疗效。

队列包括372例患者（274无肝硬化，89代偿性肝硬化，肝硬化失代偿期）。中位随访期为20个月。结果如下：

    实现病毒学应答的累积概率为68％在48周，144周和93％。
    病毒学应答无明显影响基线疾病的严重程度。
    开发了13例患者的临床事件（失代偿期，6肝癌，3死亡，7）。
    开发临床事件的概率是较高的肝硬化患者（危险比为15.4; 95％置信区间为3.4-69.5）。
    病毒学反应是与发展肝硬化患者临床事件的风险降低（HR = 0.22，P = 0.04）。
    使用一个阈值，HBV DNA <2000 IU /毫升，病毒学应答不再开发临床事件的风险降低（HR = 0.20，P = 0.10）有关。

评论：这家大型队列研究表明，恩替卡韦不仅能有效地抑制乙肝病毒患者各级肝脏疾病的严重程度，但更重要的是在那些与肝硬化，改善临床预后。我怀疑是因为缺乏见于肝硬化患者无临床受益相对较短的随访期间。由于该队列研究归于更随访时间，我期待跨越各级疾病的严重程度，临床病毒学应答的好处将是显而易见的。这项研究还强调，病毒学应答需要要积极的治疗获益。

- 与Atif扎曼，MD，MPH

期刊观看消化科2013年4月19日发布
引用（S）：

Zoutendijk R等。病毒学应答恩替卡韦治疗慢性乙型肝炎肝硬化患者具有更好的临床结果相关。肠道2013年5月，62:760。 （http://dx.doi.org/10.1136/gutjnl-2012-302024）

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