B型肝炎病毒相关肝癌的危险分层

StephenW

http://onlinelibrary.wiley.com/doi/10.1111/jgh.12010/pdf
Risk stratification for hepatitis B virus related hepatocellular carcinoma
Chih-Lin Lin1,2,
Jia-Horng Kao3,4,5,6,*
DOI: 10.1111/jgh.12010
© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley
Publishing Asia Pty Ltd Issue

Journal of Gastroenterology and Hepatology
Accepted Article. These manuscripts have been accepted, but have not been
edited or formatted. They will be published at a future date. Additional
Information(Show All) Author InformationPublication History
Author Information
1
Department of Gastroenterology, Ren-Ai branch, Taipei City Hospital,
Taipei, Taiwan 2
Department of Psychology, National Chengchi University, Taipei, Taiwan
3
Department of Internal Medicine, National Taiwan University Hospital,
National Taiwan University College of Medicine and National Taiwan
University Hospital, Taipei, Taiwan 4 Graduate Institute of Clinical
Medicine, National Taiwan University College of Medicine and National
Taiwan University Hospital, Taipei, Taiwan 5 Hepatitis Research Center,
National Taiwan University College of Medicine and National Taiwan
University Hospital, Taipei, Taiwan 6 Department of Medical Research,
National Taiwan University College of Medicine and National Taiwan
University Hospital, Taipei, Taiwan
*Correspondence:
Prof. Jia-Horng Kao
Director and Distinguished Professor, Graduate Institute of Clinical
Medicine, National Taiwan University College of Medicine
1 Chang-Te St., Taipei 10002, Taiwan
Tel.: 886-2-23123456 ext 67307
Fax: 886-2-23825962
E-mail: kaojh@ ntu.edu.tw

Hepatitis B virus (HBV) infection is the major cause of chronic hepatitis,
cirrhosis and hepatocellular carcinoma (HCC) worldwide, especially in the
Asia-Pacific region. Several hepatitis B viral factors predictive of clinical
outcomes in HBV carriers have been identified. The REVEAL-HBV study from
Taiwan illustrated the strong association between HBV DNA level at study
entry and risk of HCC overtime . In this community-based cohort study, male
gender, older age, high serum alanineaminotransferase (ALT) level, positive
HBeAg, higher HBV DNA level, HBV genotype C infection and core promoter
mutationare independently associated with a higher risk of HCC. Another large
hospital-based ERADICATE-B cohort of Taiwanese patients further validated
the findings of REVEAL-HBV. The risk of HCC started to increase when HBV
DNA level was higher than 2000 IU/mL. Both HBV DNA and HBsAg levels
were shown to be associated with HCC development. While HBV DNA level
had better predictive accuracy than HBsAg level when investigating the overall
cohort, in patients with HBV DNA level <2000 IU/mL, HBsAg level ≥1000 IU/mL
was identified as a new independent risk factor for HCC. With the results from
REVEAL–HBV, a risk calculation for predicting HCC in non-cirrhotic patients
has been developed and validated by independent cohorts (REACH-B).Taken
together, ample evidence indicates that HBsAg level can complement HBV
DNA level in predicting HCC development, especially in HBV carriers with low
viral load. In conclusion, HBV treatment guidelines should include the risk
stratification of HCC to individualize the management of HBV carriers with
different levels of HCC risk.

StephenW

B型肝炎病毒相关肝癌的危险分层
易芝玲琳1，2，
贾鸿Kao3，4,5,6，*
DOI：10.1111/jgh.12010
©2012 - 胃肠病学和肝病基金会和Wiley
出版亚洲私人有限公司发行

[胃肠病学和肝病学杂志
接受的文章。这些手稿已被接受，但一直没
编辑或格式化。他们将刊登在未来某一日期。额外
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作者信息
1
胃肠病学系，台北市立联合医院仁爱分行，
台北，台湾2
心理学系，国立政治大学，台北，台湾
3
，国立台湾大学医学院附设医院内科部，
国立台湾大学医学院和国立台湾
台北，台湾大学医学院附设医院，研究所临床
医药，国立台湾大学医学院和国家
台大医院，台北，台湾肝炎研究中心，
国立台湾大学医学院和国立台湾
台北，台湾大学医学院附设医院，医学研究部，
国立台湾大学医学院和国立台湾
台北，台湾大学医院，
*通讯作者：
高嘉鸿教授
董事特聘教授，研究所临床
国立台湾大学医学院医学
昌德街，台北10002，台湾
电话：886-2-23123456分机67307。
传真：886-2-23825962
电子邮件：[email protected]

乙型肝炎病毒（HBV）感染是慢性肝炎的主要病因，
肝硬化和肝细胞癌（HCC）全球范围内，特别是在
亚太地区。几个B型肝炎病毒的临床预测因素
乙肝病毒携带者的结果已经确定。 REVEAL-HBV研究从
台湾阐述了强烈的相关性，HBV DNA水平研究
进入和风险的HCC加班。在这个以社区为基础的队列研究中，男性
性别，年龄较大，高血清alanineaminotransferase的（ALT）水平，积极
大三阳，较高的HBV DNA水平，HBV C基因型感染和核心启动子
mutationare独立相关的HCC的风险较高。另一个大
医院为基础的根除-B的台湾患者队列进一步验证
REVEAL-HBV的结果。肝癌的风险开始增加时，HBV
DNA水平高于2000 IU / mL的。 HBV DNA和HBsAg水平
被证明是与HCC的发展。虽然HBV DNA水平
具有较好的预测精度比HBsAg水平调查时的整体
队列中，患者的HBV DNA水平<2000 IU / mL时，HBsAg水平≥1000 IU / mL的
被确定为一个新的HCC的独立危险因素。的结果，从
REVEAL-HBV，非肝硬化患者的预测HCC的风险计算
已开发和验证由独立的族群（REACH-B）。拍摄
在一起，充分的证据表明，HBsAg水平可以补充HBV
DNA水平预测肝癌的发展，尤其是在乙肝病毒携带者低
病毒载量。总之，HBV治疗指南应包括风险
分层个性化管理的乙肝病毒携带者的肝癌
不同级别的肝癌风险。

StephenW

Over the past decade, extensive research on HBV has identified several
hepatitis B viral factors such as serum HBsAg level, viral load, genotype and
mutants as powerful contributors to disease progression of chronic hepatitis B
patients. According to several population and hospital-based cohort studies,
risk stratification for HCC in patients with chronic HBV infection has been
established in a preliminary manner. Low risk factors for HBV-related HCC
include female, younger age (≦50 years old), HBV genotype A/B, low serum
levels of ALT, HBV DNA and HBsAg. In contrast, high risk factors for
HBV-related HCC include male, advanced age (> 50 years old), HBV genotype
C/D, BCP A1762T/G1764A mutations, pre-S deletion mutations, high serum
levels of ALT, HBV DNA and HBsAg. Among them, the modifiable risk factors
are serum levels of ALT, HBV DNA and HBsAg.
In the future, multivariate risk assessment profiles for HCC should be
integrated with current HBV treatment guidelines to enable practicing
physicians to have better management of HBV carriers with different HCC
risks. Finally, risk modification through antiviral therapymay lead to the
prevention of disease progression and eventually reduce the risk of HCC
development even among those who start treatment with substantial risk
(Fig4).
在过去的十年中，大量对乙肝病毒的研究已经确定了几个
B型肝炎病毒的因素，例如血清HBsAg水平，病毒载量，基因型和
慢性乙肝疾病进展的有力贡献者突变体
患者。根据一些人口和医院为基础的队列研究，
在慢性HBV感染患者HCC危险分层
建立了一个初步的方式。低HBV相关的HCC的危险因素
包括女性，年轻的年龄（≦50岁），HBV基因型A / B，低血清
ALT，HBV DNA和HBsAg水平。相比之下，高风险因素
HBV相关的HCC包括男性，高龄（> 50岁），HBV基因型
C / D，BCP A1762T/G1764A突变，pre-S缺失突变，高血
ALT，HBV DNA和HBsAg水平。其中，可改变的危险因素
血清ALT，HBV DNA和HBsAg。
在未来，应该是多元为肝癌的风险评估概况
集成与HBV治疗指南，使执业
医生更好地管理不同的肝癌的乙肝病毒携带者
风险。最后，风险通过抗病毒therapymay修改导致
预防疾病的进展，并最终降低肝癌的风险
即使是那些开始治疗相当大的风险的发展