停止口服抗病毒药治疗慢性乙型肝炎，这在眼前吗？

StephenW

    Editorial
    Published: 17 April 2020

Stopping oral antiviral treatment to cure chronic hepatitis B, is it in sight?

    Rong Fan & Jinlin Hou

Hepatology International volume 14, pages302–304(2020)Cite this article

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The treatment of chronic hepatitis B (CHB) patients has evolved dramatically over the past two decades. Currently, oral nucleos(t)ide analogues (NA) with potent viral suppression and a high genetic barrier to resistance, i.e., entecavir, tenofovir disoproxil and tenofovir alafenamide, are recommended as first-line antivirals. Long-term NA treatment can suppress hepatitis B virus (HBV) replication, reverse liver fibrosis, and reduce the risk of hepatocellular carcinoma (HCC) [1].

In the era of oral antiviral treatment, functional cure and finite treatment are the few unmet needs left for clinicians to address. In 2012, Hadziyannis et al. linked stopping treatment to the functional cure of CHB [2]. Surprisingly, they found that treatment discontinuation could lead to as high as 40% HBsAg loss during up to 6-year post-treatment follow-up among 33 HBeAg-negative, genotype D-infected, NA-naive CHB patients who stopped adefovir monotherapy after 4–5 years of successful treatment. Non-re-treatment and higher ALT levels at the end of treatment (EOT) were associated with a higher incidence of HBsAg loss [2]. Thereafter, a growing number of studies showed that HBsAg could be cleared after stopping NA treatment due to the activation of the host immune response along with off-treatment relapse in Asian and Caucasian HBeAg-negative patients [3, 4]. In a randomized controlled trial (RCT) in Europe (FINITE study), 42 HBeAg-negative, mainly Caucasian patients stopped or continued NA therapy; 19% of the patients in the treatment cessation group achieved HBsAg loss by off-treatment week 144, whereas none of the patients in the continuation group cleared HBsAg [3]. A larger retrospective study from Taiwan also reported high HBsAg loss among 691 patients, with an annual incidence of 1.8% [4]. However, there is also strong opposition that claims that the few patients achieved HBsAg loss after treatment cessation [5, 6]. The HBsAg decline was similar between the treatment cessation and continuation groups (0.2 vs. 0.1 log10 IU/mL at off-treatment week 72) among 67 HBeAg negative, mainly Asian CHB patients in an RCT [5]. The opposite results among the above results may be explained by different ethnicities (Asian vs. Caucasian), pre-treatment HBeAg status (positive vs. negative), HBV genotypes (B and C vs. A and D) and retreatment criteria. Therefore, it is still unclear whether stopping NAs can improve the functional cure.

StephenW

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    发布时间：2020年4月17日

停止口服抗病毒药治疗慢性乙型肝炎，这在眼前吗？

    范荣＆侯金林

《国际肝病学》第14卷，第302-304页（2020年）

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在过去的二十年中，慢性乙型肝炎（CHB）患者的治疗取得了巨大的进步。目前，推荐将具有强效病毒抑制作用和高抗药性遗传屏障的口服核苷（t）ide类似物（即恩替卡韦，替诺福韦二吡咯烷和替诺福韦阿拉芬酰胺）作为一线抗病毒药。长期NA治疗可以抑制乙型肝炎病毒（HBV）的复制，逆转肝纤维化，并降低患肝细胞癌（HCC）的风险[1]。

在口服抗病毒治疗的时代，功能治疗和有限治疗是临床医生需要解决的少数未满足的需求。在2012年，Hadziyannis等人。将停止治疗与CHB的功能性治疗联系起来[2]。令人惊讶的是，他们发现，在33名HBeAg阴性，基因型D感染，NA初治的CHB患者中，终止治疗后长达6年的随访期间，治疗中断可能导致高达40％的HBsAg丢失，这些患者在术后停止阿德福韦单药治疗成功治疗4-5年。未经再治疗和治疗结束时（EOT）ALT水平升高与HBsAg丢失发生率升高相关[2]。此后，越来越多的研究表明，在亚洲和白种人的HBeAg阴性患者中，由于宿主免疫应答的激活以及治疗后复发，停止NA治疗后可以清除HBsAg [3，4]。在欧洲的一项随机对照试验（RCT）中（FINITE研究），有42例HBeAg阴性，主要是白人患者停止或继续进行NA治疗。戒断组中有19％的患者在第144周停药后达到HBsAg丢失，而继续治疗组中没有一名患者清除HBsAg [3]。来自台湾的一项较大的回顾性研究也报告了691例患者中高HBsAg丢失，年发生率为1.8％[4]。但是，也有强烈的反对意见声称治疗停止后很少有患者出现HBsAg丢失[5，6]。在接受RCT的67例HBeAg阴性（主要是亚洲CHB患者）中，停止治疗和继续治疗组之间的HBsAg下降相似（治疗结束后第72周为0.2 vs. 0.1 log10 IU / mL）[5]。上述结果中相反的结果可能由不同种族（亚洲人与白种人），治疗前HBeAg状态（阳性与阴性），HBV基因型（B和C与A和D）和再治疗标准来解释。因此，尚不清楚停止NAs是否可以改善功能性治愈。

StephenW

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