Liu Shi, Wong Grace Lai-Hung, Fan Rong, Niu Junqi, Ma Hong, Liang Wanying, Lu Xingyu, Xie Jianping, Shang Jia, Xie Dongying, Liu Yali, Zhou Bin, Xie Qing, Peng Jie, Gao Hongbo, Rao Huiying, Chen Jinjun, Sheng Jifang, Shen Sheng, Yang Song, Dou Xiaoguang, Zhang Zhengang, Wong Vincent Wai-Sun, Hou Jinlin, Sun Jian
Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China; State Key Laboratory of Organ Failure Research, Guangzhou, China; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education, Guangzhou, China; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases, Guangzhou, China; Guangdong Provincial Clinical Research Center for Viral Hepatitis, Guangzhou, China.
Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
Clin Gastroenterol Hepatol. 2025 Feb;23(2):291-299.e15. doi: 10.1016/j.cgh.2024.07.024. Epub 2024 Aug 23.
Hepatocellular carcinoma (HCC) risk prediction models established in patients with chronic hepatitis B receiving nucleos(t)ide analogue (NA) rarely include viral factors because of mediocre predictability of traditional viral markers. Here, we investigate the role of serum hepatitis B virus (HBV) RNA, a novel biomarker, in predicting HCC risk in NA-treated patients.
A total of 1374 NA-treated patients were enrolled from 2 prospective chronic hepatitis B cohorts. Serum HBV RNA was detected at baseline, year 1, 2 and 3 of treatment. Cox proportional-hazard model was used to investigate the association of HBV RNA kinetics with HCC risk.
After a median follow-up of 5.4 years, 76 patients developed HCC. HBV RNA declines at year 1 (adjusted hazard ratio, 0.70; P = .009) and 2 (adjusted hazard ratio, 0.71; P = .016) were independently associated with HCC risk. Patients with less HBV RNA decline at year 1 (≤0.4 log copies/mL) or 2 (≤0.6 log copies/mL) had 2.22- and 2.09-folds higher HCC risk, respectively, than those with more declines. When incorporating these early on-treatment HBV RNA declines into existing HCC risk scores, including PAGE-B (age, sex, and platelets), modified PAGE-B (mPAGE-B) (age, sex, platelets, and albumin), and aMAP (age, sex, platelets, and albumin-bilirubin score) score, they could enhance their predictive performance (ie, C-index 0.814 vs 0.78 [model vs PAGE-B score based on baseline parameters]).
Serum HBV RNA declines at year 1 and 2 were significantly associated with on-treatment HCC risk. Incorporating early on-treatment HBV RNA declines into HCC risk prediction models can be useful tools to guide appropriate surveillance strategies in NA-treated patients.
由于传统病毒标志物的预测能力一般，在接受核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者中建立的肝细胞癌（HCC）风险预测模型很少纳入病毒因素。在此，我们研究新型生物标志物血清乙型肝炎病毒（HBV）RNA在预测接受NA治疗患者的HCC风险中的作用。
从2个前瞻性慢性乙型肝炎队列中纳入了总共1374例接受NA治疗的患者。在基线、治疗第1年、第2年和第3年检测血清HBV RNA。采用Cox比例风险模型研究HBV RNA动力学与HCC风险的关联。
中位随访5.4年后，76例患者发生了HCC。治疗第1年（调整后风险比，0.70；P = .009）和第2年（调整后风险比，0.71；P = .016）时HBV RNA下降与HCC风险独立相关。治疗第1年（≤0.4 log拷贝/mL）或第2年（≤0.6 log拷贝/mL）HBV RNA下降较少的患者发生HCC的风险分别比下降较多的患者高2.22倍和2.09倍。将这些治疗早期的HBV RNA下降纳入现有的HCC风险评分，包括PAGE - B（年龄、性别和血小板）、改良PAGE - B（mPAGE - B）（年龄、性别、血小板和白蛋白）以及aMAP（年龄、性别、血小板和白蛋白 - 胆红素评分）评分后，它们可以提高预测性能（即C指数从0.78提高到0.814[模型 与基于基线参数的PAGE - B评分相比]）。
治疗第1年和第2年时血清HBV RNA下降与治疗期间HCC风险显著相关。将治疗早期的HBV RNA下降纳入HCC风险预测模型可成为指导接受NA治疗患者采取适当监测策略的有用工具。
