Ha Yeonjung, Lim Jihye, Chon Young Eun, Kim Mi Na, Lee Joo Ho, Kim Kang Mo, Shim Ju Hyun, Lee Danbi, Hwang Seong Gyu, Han Seungbong, Lee Han Chu
Department of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam-si, South Korea.
Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Int J Cancer. 2023 Dec 15;153(12):2045-2054. doi: 10.1002/ijc.34704. Epub 2023 Aug 24.
Considering the lower risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving long-term potent antiviral therapy, models predicting HCC after 5 years of therapy are needed. We conducted a multicenter retrospective cohort study to construct and validate a model predicting HCC after 5 years of entecavir (ETV) or tenofovir (TFV) therapy for CHB. The endpoint was HCC after 5 years of ETV/TFV therapy. Information on age, sex, liver cirrhosis (assessed by diagnosis code and confirmed by clinical findings) and type of antiviral agent was obtained at baseline (initiation of ETV/TFV). Laboratory values were collected at baseline and 5 years. Risk factors for HCC were identified in the training set and the final prediction model was validated using the test set. Among 7542 patients, 345 (4.6%) developed HCC after 5 years of ETV/TFV therapy. HCC risk after 5 years of ETV/TFV therapy was increased by 4-fold in patients with liver cirrhosis than in those without cirrhosis at baseline. Furthermore, Platelet counts and Prothrombin time at 5 years, Age at baseline and Sex were associated with risk of HCC and were incorporated into a prediction model, PPACS. PPACS showed a good performance with a time-dependent area under the curve of 0.80 (95% confidence interval, 0.75-0.85) at 8-year of ETV/TFV therapy, a Brier score of 0.031 and an integrated Brier score of 0.006 in the test set. In conclusion, the PPACS model provides a reliable assessment of HCC risk after 5 years of ETV/TFV therapy (https://ppacs.shinyapps.io/shiny_app_up/).
鉴于接受长期强效抗病毒治疗的慢性乙型肝炎（CHB）患者发生肝细胞癌（HCC）的风险较低，需要建立能预测治疗5年后HCC发生情况的模型。我们开展了一项多中心回顾性队列研究，以构建并验证一个预测CHB患者接受恩替卡韦（ETV）或替诺福韦（TFV）治疗5年后发生HCC的模型。研究终点为ETV/TFV治疗5年后发生的HCC。在基线期（开始ETV/TFV治疗时）获取患者的年龄、性别、肝硬化情况（通过诊断编码评估并经临床检查确认）及抗病毒药物类型等信息。在基线期和5年时收集实验室检查值。在训练集中确定HCC的危险因素，并使用测试集对最终的预测模型进行验证。在7542例患者中，345例（4.6%）在ETV/TFV治疗5年后发生了HCC。与基线时无肝硬化的患者相比，基线时有肝硬化的患者在ETV/TFV治疗5年后发生HCC的风险增加了4倍。此外，5年时的血小板计数和凝血酶原时间、基线时的年龄及性别与HCC风险相关，并被纳入一个预测模型PPACS。在ETV/TFV治疗8年时，PPACS在测试集中表现良好，时间依赖性曲线下面积为0.80（95%置信区间，0.75 - 0.85），Brier评分为0.031，综合Brier评分为0.006。总之，PPACS模型为ETV/TFV治疗5年后HCC风险提供了可靠评估（https://ppacs.shinyapps.io/shiny_app_up/）。
