Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School of Health Sciences, University of Bern, Bern, Switzerland.
J Hepatol. 2023 May;78(5):947-957. doi: 10.1016/j.jhep.2022.12.029. Epub 2023 Jan 21.
BACKGROUND & AIMS: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. METHODS: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. RESULTS: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10-17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03-3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61-1.25), and the pooled c-index was 0.77 (range 0.73-0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. CONCLUSIONS: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. IMPACT AND IMPLICATIONS: Chronic HBV infection is the most important cause of hepatocellular carcinoma (HCC) among people living with HIV. Valid risk prediction may enable better targeting of HCC screening efforts to high-risk individuals. We aimed to validate PAGE-B, a risk prediction tool that is based on age, sex, and platelets, in 2,963 individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy. In the present study, PAGE-B showed good discrimination, adequate calibration, and a cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. These results indicate that PAGE-B is a simple and valid risk prediction tool to determine the need for HCC screening among people living with HIV and HBV.
背景与目的：乙型肝炎病毒（HBV）合并感染在人类免疫缺陷病毒（HIV）感染者中很常见，也是肝细胞癌（HCC）的最重要原因。虽然 HCC 的风险预测工具已经在 HBV 单感染患者中得到验证，但尚未在 HIV 感染者中进行评估。因此，我们对 HIV/HBV 合并感染患者中的 PAGE-B 进行了外部验证。
方法：我们纳入了来自四个欧洲队列的 HIV 阳性且在开始使用替诺福韦前未发生 HCC 的 PLWH 数据。我们估计了 PAGE-B 在接受含替诺福韦的抗逆转录病毒治疗的患者中预测 15 年内 HCC 发生的性能。使用 Cox 回归，将预测指数作为协变量进行模型判别评估，并通过计算 Harrell's c-指数进行评估。通过比较 Kaplan-Meier 曲线，比较我们的累积发生率与 PAGE-B 推导研究，评估校准。
结果：共纳入 2963 例接受含替诺福韦的抗逆转录病毒治疗的 HIV/HBV 合并感染患者。PAGE-B<10 的患者占 26.5%，10-17 的患者占 57.7%，≥18 的患者占 15.7%。在中位随访 9.6 年后，有 68 例患者发生 HCC（2.58/1000 患者-年，95%CI 2.03-3.27）。在 15 年内发展为 HCC 的预测指数的回归斜率为 0.93（95%CI 0.61-1.25），合并的 c-指数为 0.77（范围 0.73-0.80），均表明模型判别良好。与推导研究相比，我们的研究中 HCC 的累积发生率较低。PAGE-B<10 的截断值对 5 年内 HCC 发生的阴性预测值为 99.4%。将 PAGE-B≥10 的患者作为限制条件，可避免对 27%的患者进行不必要的 HCC 筛查。
结论：对于 HIV/HBV 合并感染患者，PAGE-B 是确定 HCC 筛查需求的有效工具。
影响和意义：慢性 HBV 感染是 HIV 感染者发生肝细胞癌（HCC）的最重要原因。有效的风险预测可能使 HCC 筛查工作能够更好地针对高危人群。我们旨在验证 PAGE-B，这是一种基于年龄、性别和血小板的风险预测工具，在 2963 例接受含替诺福韦的抗逆转录病毒治疗的 HIV/HBV 合并感染患者中进行验证。在本研究中，PAGE-B 显示出良好的判别能力、适当的校准能力，且截断值<10 对 5 年内 HCC 发生的阴性预测值为 99.4%。这些结果表明，PAGE-B 是一种简单有效的风险预测工具，可用于确定 HIV 和 HBV 感染者是否需要进行 HCC 筛查。
Discov Oncol. 2025-8-11
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