开发评分系统预测慢性乙型肝炎抗病毒药物对亚洲人的肝细

StephenW

J Hepatol. 2018 Mar 15. pii: S0168-8278(18)30170-3. doi: 10.1016/j.jhep.2018.02.032. [Epub ahead of print]
Development of a scoring system to Predict Hepatocellular Carcinoma in Asians on Antivirals for Chronic Hepatitis B.Hsu YC1, Cheuk-Fung Yip T2, Ho HJ3, Wai-Sun Wong V2, Huang YT4, El-Serag HB5, Lee TY6, Wu MS7, Lin JT8, Lai-Hung Wong G9, Wu CY10.
Author information
1Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan; Division of Gastroenterology and Hepatology, E-Da Hospital, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.2Institute of Digestive Disease, Hong Kong; Department of Medicine and Therapeutics, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong.3Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan.4Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.5Section of Gastroenterology and Hepatology, Department of Medicine, Michael E DeBakey VA Medical Center and Baylor College of Medicine, Houston Texas, USA.6Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Medicine, Chung Shan Medical University, Taichung, Taiwan.7Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.8Big Data Research Center, School of Medicine, Fu-Jen Catholic University, New Taipei, Taiwan; Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.9Institute of Digestive Disease, Hong Kong; Department of Medicine and Therapeutics, Hong Kong; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong. Electronic address: [email protected].10Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan; Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine and Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health, China Medical University, Taichung, Taiwan; National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan. Electronic address: [email protected].

AbstractBACKGROUND & AIMS: The risk of hepatocellular carcinoma (HCC) during antiviral therapy in patients with chronic hepatitis B (CHB) is inadequately predicted by the scores built from untreated patients. We aimed to develop and validate a risk score to predict HCC in CHB patients on entecavir or tenofovir treatment.
METHODS: This study analyzed population-wide data from the healthcare databases in Taiwan and Hong Kong to identify CHB patients continuously receiving entecavir or tenofovir. The development cohort included 23,851 patients from Taiwan; 596 (2.50%) of them developed HCC with a 3-year cumulative incidence of 3.56% (95% CI, 3.26-3.86%). The multivariable Cox proportional hazard model found cirrhosis, age (cirrhosis and age interacted with each other), male sex, and diabetes mellitus were the risk determinants. These variables were weighted to develop the CAMD score ranging from 0 to 19 points. The score was externally validated in 19,321 patients from Hong Kong.
RESULTS: The c indices for HCC in the development cohort were 0.83 (95% CI, 0.81-0.84), 0.82 (95% CI, 0.81-0.84), and 0.82 (95% CI, 0.80-0.83) at the first, second, and third year of therapy, respectively. In the validation cohort, the c indices were 0.74 (95% CI, 0.71-0.77), 0.75 (95% CI, 0.73-0.78), and 0.75 (95% CI, 0.72-0.77) during the first 3 years, and 0.76 (95% CI, 0.74-0.78) and 0.76 (95% CI, 0.74-0.77) in the extrapolated fourth and fifth years. The predicted and the observed probabilities of HCC were calibrated in both cohorts. A score <8 and >13 points identified patients at distinctly low and high risks.
CONCLUSIONS: The easily calculable CAMD score can predict HCC and may inform surveillance policy in CHB patients during oral antiviral therapy.
LAY SUMMARY: This study analyzes population-wide data from the healthcare systems in Taiwan and Hong Kong to develop and validate a risk score that predicts hepatocellular carcinoma (HCC) during oral antiviral therapy in patients with chronic hepatitis B (CHB). The easily calculable CAMD score requires only simple information (i.e., cirrhosis, age, male sex, and diabetes mellitus) at the baseline of treatment initiation. With a scoring range from 0 to 19 points, the CAMD score discriminates the risk of HCC with a concordance rate around 75∼80% during the first 3 years on therapy. The risk prediction can be extrapolated to 5 years on treatment with similar accuracy. Patients with a score <8 and >13 points were exposed to distinctly lower and higher risks, respectively.

Copyright © 2018. Published by Elsevier B.V.

KEYWORDS: Health authority; Hepatitis B virus infection; National health insurance research database; Nucleos(t)ide analogues; Risk prediction

PMID:29551708DOI:10.1016/j.jhep.2018.02.032

StephenW

J Hepatol。 2018年3月15日。pii：S0168-8278（18）30170-3。 doi：10.1016 / j.jhep.2018.02.032。 [电子版提前打印]
开发评分系统预测慢性乙型肝炎抗病毒药物对亚洲人的肝细胞癌
Hsu YC1，卓焯业T2，何HJ3，黄伟孙V2，黄YT4，El-Serag HB5，李TY6，吴MS7，林JT8，黄丽红G9，吴CY10。
作者信息

1
    台湾新北福仁大学医学院大数据研究中心;台湾新北福仁天主教大学医院消化科;高雄市艾达医院消化科和肝病科;中国医科大学临床医学研究所，台湾台中。
2
    香港消化疾病研究所;香港医学及治疗学系;香港中文大学消化疾病国家重点实验室，香港。
3
    台中台中军区总医院消化科。
4
    中国科学院统计科学研究所台湾台北。
五
    美国德克萨斯州休斯敦医学院消化与肝病学系Michael E. DeBakey VA医学中心和Baylor医学院。
6
    台中台中军区总医院消化科，台中;台湾中山医科大学医学系。
7
    台湾台北大学附属医院内科。
8
    台湾新北福仁大学医学院大数据研究中心;台湾新北辅仁大学附属医院消化科。
9
    香港消化疾病研究所;香港医学及治疗学系;香港中文大学消化疾病国家重点实验室，香港。电子地址：[email protected]。
10
    中国医科大学临床医学研究所台湾台中;台中台中军区总医院消化科，台中;国立阳明大学医学院临床医学研究所，台湾台北;台湾台中中国医科大学公共卫生系;台湾苗栗国立卫生研究院国家癌症研究所。电子地址：[email protected]。

抽象
背景＆目标：

慢性乙型肝炎（CHB）患者在抗病毒治疗过程中发生肝细胞癌（HCC）的风险未被未经治疗的患者建立得分所预测。我们旨在开发和验证风险评分，以预测恩替卡韦或替诺福韦治疗慢性乙型肝炎患者的HCC。
方法：

这项研究分析了台湾和香港医疗保健数据库中的人口数据，以确定持续接受恩替卡韦或替诺福韦的CHB患者。发展队列包括来自台湾的23851名患者;其中596名（2.50％）发展为HCC，3年累计发病率为3.56％（95％CI，3.26-3.86％）。多变量Cox比例风险模型发现，肝硬化，年龄（肝硬化和年龄相互影响），男性和糖尿病是风险的决定因素。对这些变量进行加权以制定0-19分的CAMD得分。该分数在19,321名来自香港的患者中得到了外部验证。
结果：

在开发队列中，HCC的c指数分别为0.83（95％CI，0.81-0.84），0.82（95％CI，0.81-0.84）和0.82（95％CI，0.80-0.83）第三年的治疗，分别。在验证队列中，前3年c指数分别为0.74（95％CI，0.71-0.77），0.75（95％CI，0.73-0.78）和0.75（95％CI，0.72-0.77），以及0.76 （95％CI，0.74-0.78）和0.76（95％CI，0.74-0.77）在外推的第四和第五年。预测和观察到的HCC概率在两个队列中进行了校准。评分<8和> 13分确定了患者风险明显低和高。
结论：

易于计算的CAMD评分可以预测HCC，并可能在CHB患者口服抗病毒治疗期间通知监测政策。
总结：

这项研究分析了台湾和香港医疗系统的人群范围数据，旨在开发和验证在慢性乙型肝炎（CHB）患者口服抗病毒治疗期间预测肝细胞癌（HCC）风险评分。易于计算的CAMD评分仅需要在治疗开始的基线处的简单信息（即，肝硬化，年龄，男性和糖尿病）。评分范围从0到19分，CAMD评分在治疗的前3年内可以区分HCC的一致率为75〜80％。风险预测可以外推到5年，治疗的准确性相似。分数<8和> 13分的患者分别暴露于明显更低和更高的风险。

版权所有©2018. Publis

StephenW

Novel score predicts liver cancer risk during HBV antiviral therapy

Hsu YC, et al. J Hepatol. 2018;doi:10.1016/j.jhep.2018.02.032.
March 23, 2018

Researchers developed a predictive risk score for the development hepatocellular carcinoma during oral antiviral therapy in patients with chronic hepatitis B, according to recently published data.

“The score requires simple information that is readily available in all treated patients,” Yao-Chun Hsu, MD, from the Fu-Jen Catholic University, Taiwan, and colleagues wrote. “By stratifying patients at different risks of HCC, the easily applicable score may inform the clinical practice and healthcare policy in the era of antiviral treatment for [chronic HBV].”


To develop the predictive tool, Hsu and colleagues analyzed data on patients from the National Health Insurance Research Database (NHIRD) in Taiwan and the Hospital Authority (HA) database in Hong Kong who received entecavir or tenofovir for chronic HBV.

The researchers selected the patients from Taiwan to develop the score and patients from Hong Kong to validate its efficacy. Patients from Taiwan and those from Hong Kong differed significantly by age, sex distribution, presence of cirrhosis, medication exposure and presence of diabetes (P < .001).

The final adjusted model from the development cohort showed that presence of cirrhosis, age, male sex and the presence of diabetes independently correlated with an increased risk for HCC. Cirrhosis and age also significantly interacted with each other in association with HCC.

The researchers refer to the combined factors as the CAMD score, which ranges from 0 to 19 points, and determined that a score of less than 8 points demonstrated a low risk for HCC, between 8 points and 13 points demonstrated an intermediate risk, and a score higher than 13 points was considered high-risk.

In the validation cohort, the 3-year cumulative incidences of HCC were 0.72% (95% CI, 0.49-0.94) for patients with a score of less than 8 points, 3.35% (95% CI, 2.93-3.76) for those with a score between 8 points and 13 points, and 9.17% (95% CI, 7.29-11.05) for those with more than 13 points. Similarly, the 5-year cumulative incidences of HCC were 0.91% (95% CI, 0.64-1.19%) for patients with 8 points, 4.95% (95% CI, 4.37-5.52%) for those between 8 points and 13 points, and 13.62% (95% CI, 11.21-16.04%) among the high-risk patients with more than 13 points.

“The risk of HCC in patients with [chronic HBV] is not static during the antiviral therapy,” the researchers wrote. “We and others have shown that the HCC incidence significantly decreased over the years on treatment. However, it remains elusive whether a prolonged therapy can eventually eliminate the risk and if so, how long the regimen should be.” – by Talitha Bennett

Disclosure: Hsu reports he served as an advisory committee member for Gilead Sciences and received lecture fees from AbbVie, Bristol-Myers Squibb and Gilead Sciences.

StephenW

新评分可预测HBV抗病毒治疗期间的肝癌风险

Hsu YC等人J Hepatol。 2018; DOI：10.1016 / j.jhep.2018.02.032。
2018年3月23日

根据最近公布的数据，研究人员在慢性乙型肝炎患者的口服抗病毒治疗期间为发展中的肝细胞癌制定了预测风险评分。

“评分要求所有治疗患者都能获得简单的信息，”来自台湾辅仁大学的Yao-Chun Hsu博士及其同事写道。 “通过对患有不同HCC风险的患者进行分层，易于使用的分数可以为[慢性HBV]抗病毒治疗时代的临床实践和医疗保健政策提供信息。”
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为开发预测工具，Hsu及其同事分析了台湾国家健康保险研究数据库（NHIRD）和香港医院管理局（HA）数据库中接受恩替卡韦或替诺福韦治疗慢性HBV的患者的数据。

研究人员选择了台湾的患者来开发评分和来自香港的患者，以验证其疗效。来自台湾和香港的患者年龄，性别分布，肝硬化，药物暴露和糖尿病存在显着差异（P <0.001）。

来自发展队列的最终调整模型显示，肝硬化，年龄，男性和糖尿病的存在与HCC风险增加独立相关。与肝癌相关的肝硬化和年龄也显着相互影响。

研究人员将综合因子称为CAMD评分，范围从0到19分，并且确定低于8分的评分显示HCC低风险，8分和13分之间显示中等风险，高于13分的分数被认为是高风险的。

在验证队列中，HCC 3年累积发生率分值低于8分的患者为0.72％（95％CI，0.49-0.94），对于患有HCC的患者为3.35％（95％CI，2.93-3.76）得分在8分和13分之间，超过13分的得分为9.17％（95％CI，7.29-11.05）。同样，HCC的5年累积发生率为8分至13分的患者分别为0.91％（95％CI，0.64-1.19％），4.95％（95％CI，4.37-5.52％），和13.62％（95％CI，11.21-16.04％）高于13分的高危患者。

研究人员写道：“[慢性HBV]患者发生HCC的风险在抗病毒治疗期间不是静止的。 “我们和其他人已经表明，治疗后多年来HCC发病率显着下降。然而，延长治疗是否最终可以消除风险，如果是，治疗方案应该维持多久，仍然是难以捉摸的。“ - Talitha Bennett

披露：Hsu报告说，他曾担任Gilead Sciences的咨询委员会成员，并从AbbVie，Bristol-Myers Squibb和Gilead Sciences收到演讲费。