来信：乙肝转阴表面确实降低肝癌风险

StephenW

Letter: hepatitis B surface seroclearance does reduce the risk of hepatocellular carcinoma

    Y. C. Chen andY. F. Liaw
   
    Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

Email: Y. C. Chen ([email protected])
Version of Record online: 13 JUN 2016

DOI: 10.1111/apt.13674

© 2016 John Wiley & Sons Ltd

Issue
Alimentary Pharmacology & Therapeutics

Volume 44, Issue 2, pages 210–211, July 2016



Sirs,

We read with great interest the nested case–control study by Gounder et al.[1] The study included 238 case patients and 435 control patients with sex, genotype and age-matched at cohort entry, and concluded that hepatitis B surface antigen (HBsAg) seroclearance was not associated with reduced risk of hepatocellular carcinoma (HCC) development. This is contradictory to observations of previous studies that HCC could occur at a lower rate after HBsAg seroclearance.[2-4] A most recent systematic review with meta-analysis has shown that HBsAg seroclearance is significantly associated with a reduced risk for HCC compared with persistently positive HBsAg (relative risk = 0.34, 95% CI: 0.20–0.56, P < 0.001).[5]

The following points require clarification/further discussion. First, as HCC development can be reduced by anti-viral treatment,[6, 7] anti-viral therapy in two of the case patients before HBsAg seroclearance and 32 control patients may have biased the results. What would be the results if these patients were excluded? Second, age ≥50 years at the time of HBsAg seroclearance is a risk factor for HCC development.[3, 8] The age at the time of HBsAg seroclearance was not reported in this study, but three of the four case patients who developed HCC were of advanced age and the remaining one was cirrhotic. Given the age at cohort entry of 28.8 years and a follow-up period of 28.9 years from cohort entry in case-patients, the median age at HBsAg seroclearance can be calculated to be 57.7 years, which is much higher than the age (45–51 years) reported in previous studies.[2-4] Third, HBV DNA was detected in 48% of case patients after HBsAg seroclearance for ≥9 years. This is extremely high as compared with 1–14.3% ever reported in the literatures,[3, 9] including that in their own previous study (17.7%).[10] Perhaps old age at HBsAg seroclearance and high proportion of viremia after HBsAg seroclearance might increase the HCC development in the study by Gounder's et al.[1] More information is needed for a valid discussion.
Acknowledgements

Declaration of personal interests: YC Chen have no financial and personal relationships with other people or organisations that could inappropriately influence (bias) their work. YF Liaw has involved in clinical trials or served as a global advisory board member of Roche.

Declaration of funding interests: None.
References

    1
    Gounder PP, Bulkow LR, Snowball M, et al. Nested case-control study: hepatocellular carcinoma risk after hepatitis B surface antigen seroclearance. Aliment Pharmacol Ther 2016; 43: 1197–207.

StephenW

来信：乙肝转阴表面确实降低肝癌风险

    Y. C.陈安迪。 F.廖
   
    肝病研究单位，长庚医院，医学长庚大学，台湾台北

电子邮件：Y. C.陈（[email protected]）
2016年6月13日：记录在线版本

DOI：10.1111 / apt.13674

2016年©约翰·威利父子有限公司

问题
消化系统药理学和治疗

第44卷第2期，页210-211，2016年七月



先生们，

我们通过Gounder等人以极大的兴趣阅读的巢式病例对照研究。[1]该研究共纳入238的情况下患者和435控制病人的性别，基因型和年龄相匹配的队列的条目，并得出结论：乙肝表面抗原（HBsAg ）血清学清除没有与肝细胞癌（HCC）的发展风险降低。这是矛盾的以前的研究HCC可能发生在乙肝表面抗原血清学清除后低税率的意见。[2​​-4]一个最近的系统与荟萃分析的审查表明，乙肝表面抗原血清学清除是显著为肝癌的风险降低相比相关持续HBsAg阳性者（相对危险= 0.34，95％CI：0.20-0.56，P <0.001）[5]。

以下几点需要澄清/进一步讨论。首先，如肝癌的发展可通过抗病毒治疗，[6,7]抗病毒治疗中的两个的HBsAg血清清除之前的情况下的患者和32名对照患者减少可能施力的结果。会是什么，如果这些患者被排除的结果？其次，年龄≥50岁的HBsAg在转阴的时间是肝癌的危险因素。[3,8]在乙肝表面抗原血清学清除时的年龄在本研究中没有报道，但三谁开发HCC的四个病例患者是高龄的，剩余的一个是肝硬化。给定的年龄的28.8年队列条目，并从在病例患者队列条目28.9年一个随访期间，中位年龄在HBsAg的血清清除可被计算为57.7年，这比在年龄高得多（45- 51年）报道在以往的研究。[2-4]第三，HBV DNA是在病人的情况下48％的乙肝表面抗原检测转阴后≥9年。这是非常高的，在文献曾报道1-14.3％，相比[3,9]，包括在自己以前的研究中（17.7％）。[10]也许是晚年的乙肝表面抗原血清学清除和病毒血症后HBsAg的比例高可能血清清除由Gounder的等增加在研究肝癌发展是需要一个有效的讨论[1]的更多信息。
致谢

个人利益声明：YC晨​​与其他人或组织可能不适当地影响（偏差），他们的工作没有财务和个人关系。 YF廖曾参与临床试验或担任罗氏的全球顾问委员会的成员。

资金申报利益：无。
参考

    1
    Gounder PP，Bulkow LR，雪球M，等。巢式病例对照研究：乙肝表面抗原血清学清除后肝癌的风险。滋养品药理疗法2016年; 43：1197-207。

囧大叔

问题是 根本就不能转阴，太难了。。。

zgct

乙肝表面抗原（HBsAg ）血清学清除没有与肝细胞癌（HCC）的发展风险降低。这句话什么意思？就表面抗原下降，得肝Ca风险下降，如果表面抗原转阴则Ca更低？

zgct

好文

疯一点好

其次，年龄≥50岁的HBsAg在转阴的时间是肝癌的危险因素


这句话更可怕，是否说明这个年龄段转阴反而导致肝癌高发。

四十己过

希望如论文所描述，如像我这样逐年自然下降，从2014年4500+到2015年3100+到2016年2300+IU。看来像缪医生和骆老说的，四十岁后可预期乐观~

疯一点好

@ StephenW

能否看一下原文这段说法：其次，年龄≥50岁的HBsAg在转阴的时间是肝癌的危险因素

是不是说在这个年龄段转阴是转为肝癌的危险因素

StephenW

回复 疯一点好 的帖子

不是. 作者(台湾廖教授)相信HBsAg转阴会降低肝癌风险.
HBsAg在年龄50岁后转阴 比 HBsAg在年龄50岁之前转阴的肝癌风险高.

我的观点:
1. 50只是一个一般指标，而不是绝对;
2. 年龄高患癌症的风险（不只是肝脏癌症）也高.

疯一点好

感谢斯蒂芬的解释，这样说就非常清楚了，我是2014年发现转阴的，这个年纪转阴没什么意义了，最大的期望还是希望能够有防癌的方法。