慢性乙型肝炎的HCC预测模型：14种模型的系统评价和外部验证

StephenW

HCC prediction models in chronic hepatitis B: a systematic review of 14 models and external validation
Shanshan Wu  1 , Na Zeng  1 , Feng Sun  2 , Jialing Zhou  3 , Xiaoning Wu  3 , Yameng Sun  3 , Bingqiong Wang  3 , Siyan Zhan  2 , Yuanyuan Kong  1 , Jidong Jia  4 , Hong You  5 , Hwai-I Yang  6
Affiliations
Affiliations

    1
    National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China,100050.
    2
    Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, Mainland China, 100191.
    3
    Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China, 100050.
    4
    National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China,100050; Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China, 100050.
    5
    National Clinical Research Center of Digestive Diseases, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China,100050; Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University, Beijing, Mainland China, 100050. Electronic address: [email protected].
    6
    Genomics Research Center, Academia Sinica, Taipei, Taiwan; Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: [email protected].

    PMID: 33667678 DOI: 10.1016/j.cgh.2021.02.040

Abstract

Background & aims: The aim of our study was to characterize the performance of hepatocellular carcinoma (HCC) prediction models in chronic hepatitis B (CHB) patients through meta-analysis followed by external validation.

Methods: We performed a systematic review and meta-analysis of current literature, followed by external validation in independent multi-center cohort with 986 patients with CHB undergoing entecavir treatment (median follow-up: 4.7 years). Model performance to predict HCC within 3, 5, 7, and 10 years was assessed using area under receiver operating characteristic curve (AUC) and calibration index. Subgroup analysis were conducted by treatment status, cirrhotic, race and baseline alanine aminotransferase.

Results: We identified 14 models with 123,885 patients (5,452 HCC cases), with REACH-B, CU-HCC, GAG-HCC, PAGE-B and mPAGE-B models being broadly externally validated. Discrimination was generally acceptable for all models, with pooled AUC ranging from 0.70 (95%CI, 0.63-0.76 for REACH-B) to 0.83 (95%CI, 0.78-0.87 for REAL-B) for 3-year, 0.68 (95%CI, 0.64-0.73 for REACH-B) to 0.81 (95%CI, 0.77-0.85 for REAL-B) for 5-year and 0.70 (95%CI, 0.58-0.80 for PAGE-B) to 0.81 (95%CI, 0.78-0.84 for REAL-B and 0.77-0.86 for AASL-HCC) for 10-year prediction. However, calibration performance was poorly reported in most studies. In external validation cohort, REAL-B showed highest discrimination with 0.76 (95%CI, 0.69-0.83) and 0.75 (95%CI, 0.70-0.81) for 3 and 5-year prediction. The REAL-B model was also well calibrated in the external validation cohort (3-year Brier score 0.066). Results were consistent in subgroup analyses.

Conclusions: In a systematic review of available HCC models, the REAL-B model exhibited best discrimination and calibration.

Keywords: Hepatocellular carcinoma; chronic hepatitis B; external validation; meta-analysis; prediction model.

Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.

StephenW

慢性乙型肝炎的HCC预测模型：14种模型的系统评价和外部验证
吴珊珊1，娜增1，孙风2，周嘉玲3，吴晓宁3，孙亚萌3，王炳琼3，四言詹2，圆圆孔1，冀东嘉4，洪佑5，杨怀一6
隶属关系
隶属关系

    1个
    首都医科大学附属北京友谊医院消化系统疾病国家临床研究中心，北京，中国大陆，100050
    2个
    北京大学健康科学中心公共卫生学院流行病学和生物统计学系，北京，中国大陆100191
    3
    首都医科大学附属北京友谊医院，肝硬化转化医学北京市重点实验室，肝研究中心，北京，中国大陆，100050。
    4
    首都医科大学附属北京友谊医院消化系统疾病国家临床研究中心，北京，中国大陆，100050；首都医科大学附属北京友谊医院，肝硬化转化医学北京市重点实验室，肝研究中心，北京，中国大陆，100050。
    5
    首都医科大学附属北京友谊医院消化系统疾病国家临床研究中心，北京，中国大陆，100050；首都医科大学附属北京友谊医院，肝硬化转化医学北京市重点实验室，肝脏研究中心，北京，中国大陆，100050。电子地址：[email protected]。
    6
    中国台湾省中央研究院基因组学研究中心；国立阳明大学临床医学研究所，台湾台北；高雄医科大学医学院医学研究生院，台湾高雄。电子地址：[email protected]。

    PMID：33667678 DOI：10.1016 / j.cgh.2021.02.040

抽象的

背景与目的：我们的研究目的是通过荟萃分析，然后通过外部验证来表征慢性乙型肝炎（CHB）患者中肝细胞癌（HCC）预测模型的性能。

方法：我们对现有文献进行了系统的回顾和荟萃分析，然后在独立的多中心队列中对986名接受恩替卡韦治疗的CHB患者进行了外部验证（中位随访时间：4.7年）。使用接收器工作特性曲线（AUC）和校准指数下的面积评估了在3、5、7和10年内预测HCC的模型性能。根据治疗状态，肝硬化，种族和基线丙氨酸氨基转移酶进行亚组分析。

结果：我们鉴定了14个模型，共123,885例患者（5,452例HCC病例），其中REACH-B，CU-HCC，GAG-HCC，PAGE-B和mPAGE-B模型得到了广泛的外部验证。对于所有模型，歧视通常是可以接受的，三年的合并AUC范围从0.70（95％CI，对于REACH-B为0.63-0.76）到0.83（95％CI，对于REAL-B为0.78-0.87），0.68（95 ％CI（对于REACH-B为0.64-0.73）至0.81（95％CI，REAL-B为0.77-0.85）为5年，以及0.70（95％CI，PAGE-B为0.58-0.80）至0.81（95％ CI，对于10年的预测为REAL-B为0.78-0.84，AASL-HCC为0.77-0.86）。但是，在大多数研究中，校准性能的报道很少。在外部验证队列中，对于3年和5年预测，REAL-B表现出最高的区分度，分别为0.76（95％CI，0.69-0.83）和0.75（95％CI，0.70-0.81）。在外部验证队列中，还对REAL-B模型进行了很好的校准（3年Brier评分为0.066）。亚组分析结果一致。

结论：在对现有HCC模型的系统评价中，REAL-B模型表现出最佳的判别和校准。

关键词：肝细胞癌；慢性乙型肝炎外部验证；荟萃分析预测模型。

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