AASLD访谈JonggiChoi教授：乙肝表面抗原清除率对肝癌根治性肝切除术后复发的影响
乙型肝炎病毒表面抗原（HBsAg）血清学清除被认为是慢性乙型肝炎（CHB）患者治疗的理想目标。以往的研究一致证明HBsAg血清学清除对肝细胞癌（HCC）发生风险存在有益影响。然而，HBsAg血清学清除对HCC根治性肝切除术后复发的影响尚不清楚。在今年的美国肝病研究学会年会（AASLD2021）期间，韩国首尔蔚山大学医学院牙山医学中心Jonggi Choi教授一公顷多少平方千米进行了一项题为“IMPACT OF HBsAg SEROCLEARANCE ON THE RECURRENCE OF HEPATOCELLULAR CARCINOMA AFTER CURATIVE LIVER RESECTION”的口头报告（AASLD2021. Oral 64.），该报告研究比较了有无实现HBsAg血清学清除患者之间的HCC复发率。本期《国际肝病》特别邀请到Jonggi Choi教授围绕该主题内容作进一步分享。
《国际肝病》：HBsAg血清学清除的相关机制是什么？此外，促进HBsAg清除或血清学转换的潜在治疗靶点有哪些？
Choi博士：HBsAg血清学清除被认为是慢性乙型肝炎患者治疗的理想目标。HBsAg血清学清除被称为功能性治愈。我们追求HBsAg消失的原因是，一旦实现HBsAg消失，我们就可以期
待更好的长期结果，包括HCC的发展。然而，实现这种功能性治愈的主要障碍是HBV的复制和HBsAg的产生有多条途径。它可能来自肝细胞中的cccDNA，也可能来自宿主细胞中整合的HBV DNA。此外，乙肝感染患者通常对乙肝病毒的免疫反应减弱。问题是HBsAg消失在乙肝感染的自然病程中很少发生。为了实现这一目标，我们一直在进行各种抗病毒治疗，但目前的抗病毒治疗，如干扰素或口服抗病毒治疗，HBsAg消失非常低。最近一些研究表明，如果停用核苷（酸）类似物（NUC），可能会增加宿主免疫HBsAg消失的机会。然而，这种NUC停药策略在亚洲患者中效果不佳，总是有肝失代偿的风险，有时对患者来说是非常危险的。考虑到乙肝感染的自然生命周期，许多靶标可能帮助清除HBsAg，实现功能性治愈。目前正在研制一些药物以阻断这些靶标。有些药物，例如抗Cp抑制剂，阻止HBV进入肝细胞。有些药物可以阻断病毒RNA的翻译。有些药物会阻止衣壳的组装。还有一种药物可以减少HBsAg分泌到血液中。这些是实现慢性乙型肝炎患者功能性治愈的潜在治疗靶标。
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Hepatology Digest: What is the relevant mechanism of HBsAg rological clearance? In
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addition, what are the potential therapeutic targets helpful to HBsAg clearance? and /or? ro-conversion?
禁毒宣传语Dr Choi: Basically, HBsAg roclearance is regarded as a realistic goal in the management of patients with chronic hepatitis B. HBsAg clearance is called a functional cure. The reason why we are pursuing HBsAg loss is that once HBsAg loss is achieved, we can expect better long-term outcomes, including for the development of HCC. However, the main barriers to achieving this functional cure is that there are many avenues for hepatitis B replication and HBsAg production. It could be from cccDNA in the hepatocyte, or it could be from integrated HBV DNA in the host cells. In addition, patients with hepatitis B infection usually have impaired immune respons against the hepatitis B virus. The problem is that HBsAg loss occurs very rarely in the natural history of hepatitis B infection. We have been treating with various antiviral treatments to achieve this goal, however the rate of HBsAg loss is very low with the current antiviral treatments, such as interferon or oral antiviral treatment. Recently, some studies have shown that if NUCs are stopped, it might increa the chance of HBsAg loss by the host’s immunity. However, thi
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漫画人物女s NUC-stopping strategy did not work well in Asian patients. This stopping strategy always carried the risk of hepatic decompensation, which is sometimes very dangerous for patients. Regarding achieving HBsAg roclearance, we have many targets for a functional cure considering the natural life cycle of hepatitis B infection. Drugs in the pipeline today try to block the targets. Some drugs, for example, anti-Cp inhibitors, do not allow HBV to enter the hepatocyte. Some drugs block translational viral RNA. And some drugs will block capsid asmbly. There is also a drug that reduces cretion of HBsAg into the blood stream. So, the are the potential therapeutic targets for achieving functional cure in patients with chronic hepatitis B.
《国际肝病》：哪些指标可预测HBsAg血清学清除？自发性和抗病毒治疗所致的HBsAg血清学清除有何异同点？
Choi博士：不幸的是，到目前为止，还没有强有力的指标来保证或预测HBsAg血清学清除率。不过一些研究报道，血液中HBsAg的滴度也许能反映自然病程和抗病毒治疗患者达到HBsAg血清学清除的可能性。HBsAg滴度越低，HBsAg清除率越高。
关于你的第二个问题，去年我们比较了自发性HBsAg丢失和治疗诱导的HBsAg丢失之间的长期结果。这项研究发表在去年的甜菜的做法Hepatology杂志上。我们的研究结论是，这两种HBsAg丢失在长期预后（包括HCC、死亡和肝移植）方面没有显著差异。换句话说，一旦实现HBsAg消失，我们就可以期待良好的预后结果。因此，基于我们的研究，方法并不重要。随后中国香港开展的一项研究也显示出与我们一致的结果。总之，目前最重要的还是如何实现HBsAg消失，以及该如何提高HBsAg丢失率。
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Hepatology Digest: What indicators can predict HBsAg rological clearance? What are the similarities and differences between the spontaneous HBsAg rological clearance and tho induced after antiviral therapy?
Dr Choi: Unfortunately, there has been no strong indicator to guarantee or predict HBsAg roclearance so far. However, some studies reported that when we measure HBsAg titer in the blood, this may reflect the possibility of HBsAg roclearance in the natural history and in patients on antiviral treatment. The lower the HBsAg titer, the higher the probability 保险营销话术
of HBsAg clearance. For your cond question, last year we compared the long-term outcomes between spontaneous HBsAg loss and treatment-induced HBsAg loss. This study was published in Hepatology last year. The conclusion of our study was that there is no significant difference in the long-term prognosis, including HCC, death and liver transplantation, between the two HBsAg loss. In other words, once HBsAg loss is achieved regardless of the way, we can expect a good prognosis. Therefore, the way is not important bad on our study. A following study from Hong Kong also showed consistent results to ours. In conclusion, the most important thing again is how we can achieve HBsAg loss and how we can increa the rates of HBsAg loss, regardless of the way.
