最近的研究报告指出，乙肝病毒（HBV）DNA中度水平与乙肝e抗原（HBeAg）阳性、非肝硬化患者的慢性乙肝（CHB）患者肝细胞癌（HCC）风险显著相关。我们的目标是开发和验证一个新的风险评分来预测进入 HBeAg 阳性 CHB 之前基线中度 HBV DNA 水平的患者的 HCC 发展情况。这项多中心队列研究在韩国的23所大学附属医院（2012-2020年）招募了3,585名 HBeAg 阳性、非肝硬化患者，他们在慢性感染过程中进入 CHB 时开始接受恩替卡韦或替诺福韦二丙酸酯抗病毒治疗。基于多变量 Cox 模型，开发了一种新的 HCC 风险评分（PAGED-B）（训练组，n=2,367）。进行了内部验证和外部验证（验证组，n=1,218）的自举法。60（1.7%）名患者发展为 HCC（中位随访时间为5.4年）。在训练组中，年龄、性别、血小板、糖尿病和中度 HBV DNA 水平（5.00-7.99 log10 IU/mL）与 HCC 的发展独立相关。PAGED-B 评分通过五个 HCC 的发展预测因子（血小板、年龄、性别、糖尿病和中度 HBV DNA）在5年内显示了一种时间相关的接收者工作特性曲线（AUROC）为0.81。在验证组中，5年的 PAGED-B 的 AUROC 为0.85，明显高于其他评分（PAGE-B、mPAGE-B、CAMD 和 REAL-B）。按照 PAGED-B 评分分层，高危患者的 HCC 风险明显高于低危患者（训练组亚分布风险比=8.43，验证组亚分布风险比=11.59，均 P<0.001）。新建立的 PAGED-B 评分可在进入 HBeAg 阳性 CHB 时进行 HCC 风险分层。该研究开发并验证了一种新的 HCC 发展风险评分，提示新建立的 PAGED-B 评分包括基线中度 HBV DNA 水平（5-8 log10 IU/ml）可提高预测性能。基于患者的年龄、性别、糖尿病状态、血小板计数和进入 CHB 时的中度 DNA 水平（5-8 log10 IU/ml），PAGED-B 评分是一个可靠且易于获取的评分，可用于预测 HBeAg 阳性患者进入 CHB 在首次5年抗病毒治疗期间的 HCC 发展。PAGED-B 评分的得分范围为0到12分，可以区分 HCC 风险。PAGED-B 评分显著区分5年的 HCC 风险：低风险＜7分，高风险≥7分。© 2023版权归Elsevier B.V.所有。

Recent studies reported that moderate hepatitis B virus (HBV) DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed at developing and validating a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection.This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in twenty-three tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n=2,367) based on multivariable Cox models. Bootstrap for internal validation and external validation (validation cohort, n=1,218) were performed.Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/mL) were independently associated with HCC development. PAGED-B score with five predictors for HCC development (platelets, age, gender, diabetes, and moderate HBV DNA) showed a time-dependent area under the receiver operating characteristics curve (AUROC) of 0.81 for 5-year HCC development. In the validation cohort, the AUROC of PAGED-B at 5-years was 0.85, significantly higher than the other scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio= 8.43 in the training and 11.59 in the validation cohorts, all P<0.001).The newly established PAGED-B score may enable risk stratification for HCC at the time of change into HBeAg-positive CHB.This study developed and validated a new risk score to predict HCC development in patients entering into HBeAg-positive CHB from chronic infection, and suggested that newly established PAGED-B score included baseline moderate HBV DNA levels (5-8 log10 IU/ml) could improve the predictive performance. A PAGED-B score, which is based on a patient's age, gender, diabetic status, platelet counts, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, represents a reliable and easily available risk score to predict HCC development during the first five years of antiviral treatment in HBeAg- positive patients entering into CHB. With a scoring range from 0 to 12 points, a PAGED-B score differentiates the HCC risk. A PAGED-B score significantly differentiates the 5-year HCC risk: low <7 points and high ≥7 points.Copyright © 2023. Published by Elsevier B.V.