HBeAg阴性慢性乙型肝炎的有限核苷酸（t）ide模拟疗法：新兴

StephenW

Finite nucleos(t)ide analog therapy in HBeAg-negative chronic hepatitis B: an emerging paradigm shift

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• Yun-Fan Liaw
  

• Yun-Fan Liaw
  
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• 1.Liver Research Unit, Chang Gung Memorial HospitalChang Gung University College of MedicineTaipeiTaiwan
  

Review ArticleFirst Online: 26 September 2019

   

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Abstract

Potent nucleos(t)ide analogs (NUC), such as entecavir and tenofovir disoproxil fumarate, are able to suppress HBV DNA to undetectable level. These agents have no direct action on cccDNA, which is a very stable template for HBV production, hence long-term or even life-long NUC therapy is required in HBeAg-negative patients to maintain HBV suppression and to achieve the ultimate goal of HBsAg loss. However, there are concerns of indefinite or life-long NUC therapy, including drug resistance, financial burden, adherence and willingness for indefinite long-term NUC therapy. Patients lost to follow-up and hence, not monitored may risk severe relapse that may deteriorate to hepatic decompensation or even hepatic failure. This Review integrated the cumulated evidence and assessed the strategy of finite NUC therapy in HBeAg-negative patients which was first tried in early 2000s. Earlier Asian findings that 2-year NUC therapy is feasible and safe have founded APASL stopping rule for patients on NUC therapy over 2–3 years since 2008. Subsequent studies have supported the strategy of finite NUC therapy, which has finally been accepted as an option by American and European liver associations since 2016. More recent studies have further shown greatly increased HBsAg loss rate (up to 5-year 39%) after stopping NUC therapy. The cumulated evidence has shown that the paradigm shift from indefinite long-term therapy to finite NUC therapy in HBeAg-negative patients is emerging. More studies are needed to fine-tuning the strategy including research for the optimal duration of consolidation therapy, timing to stop and to start re-treatment.

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KeywordsClinical relapse Entecavir Hepatitis flare Hepatic decompenation Sustained remission Tenofovir

StephenW

HBeAg阴性慢性乙型肝炎的有限核苷酸（t）ide模拟疗法：新兴的范式转变

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1.长庚大学长庚医院肝病研究组台北台湾

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首次在线：2019年9月26日

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抽象

强大的核苷酸类似物（NUC），例如恩替卡韦和替诺福韦富马酸替诺福韦酯，能够将HBV DNA抑制到无法检测的水平。这些药物对cccDNA没有直接作用，而cccDNA是产生HBV的非常稳定的模板，因此，HBeAg阴性患者需要长期甚至终生NUC治疗，以维持HBV抑制并达到HBsAg丧失的最终目的。 。但是，存在不确定或终生NUC治疗的担忧，包括耐药性，经济负担，患者，自足，自足，自足，自足，自足，自足，自足，自足，自足， HBeAg阴性患者的自给自足，自给自足，自给自足NUC治疗于2000年代初首次尝试。自2008年以来的2到3年间，亚洲较早的发现表明2年NUC治疗是可行且安全的，这为NUC治疗患者建立了APASL停药规则。随后的研究支持有限NUC治疗策略，该策略最终被接受为一种选择自2016年以来由美国和欧洲肝脏协会联合进行。最近的研究进一步表明，停止NUC治疗后，HBsAg丢失率大大提高（高达5年39％）。累积的证据表明，HBeAg阴性患者正在从不确定的长期治疗向有限的NUC治疗转变。需要做更多的研究来调整策略，包括研究巩固治疗的最佳持续时间，停止和开始重新治疗的时机。
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关键词
临床复发恩替卡韦肝炎发作肝分解持续缓解替诺福韦