Devision of Hepatology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
The Catholic University Liver Research Center, Seoul, Republic of Korea.
Am J Gastroenterol. 2021 Aug 1;116(8):1657-1666. doi: 10.14309/ajg.0000000000001219.
Antiviral therapy improves hepatic fibrosis and reduces hepatocellular carcinoma (HCC) incidence. This study aimed to evaluate whether on-therapy changes in scores for fibrosis index based on 4 factors and aspartate aminotransferase-to-platelet ratio index are associated with HCC development and establish an HCC risk score model incorporating noninvasive fibrosis marker (NFM) response.
This multicenter study recruited 5,147 patients with chronic hepatitis B (4,028 for derivation cohort and 1,119 for validation cohort) who were given entecavir/tenofovir for >12 months between 2007 and 2018. A risk prediction model for HCC was developed using predictors based on multivariable Cox models, and bootstrapping was performed for validation.
The 10-year cumulative HCC incidence rates were 12.6% and 13.7% in the derivation and validation cohorts, respectively. The risk of HCC significantly differed with early NFM response, with a marked reduction in HCC risk in patients achieving a significant decrease in NFM by 12 months (P < 0.001). NFM response, sex, age, and cirrhosis were independently predictive of HCC. We developed the Fibrosis marker response, Sex, Age, and Cirrhosis (FSAC) score based on regression coefficients of each variable. For the 10-year prediction of HCC, FSAC showed higher C-index values than PAGE-B, modified PAGE-B, CU-HCC, and REACH-B (0.84 vs 0.77, 0.80, 0.77, and 0.67, respectively; all P < 0.005). The predictive performance of FSAC was corroborated in the validation cohort, with higher C-index than other models (all P < 0.050).
On-therapy changes in NFM are an independent indicator of HCC risk. FSAC incorporating NFM response is a reliable risk score for risk estimation for HCC with better performance than other models.
抗病毒治疗可改善肝纤维化并降低肝细胞癌（HCC）的发生率。本研究旨在评估纤维化指数基于 4 个因素的评分和天门冬氨酸氨基转移酶与血小板比值指数的治疗中变化是否与 HCC 发展相关，并建立包含非侵入性纤维化标志物（NFM）反应的 HCC 风险评分模型。
这项多中心研究招募了 5147 名慢性乙型肝炎患者（4028 名用于推导队列，1119 名用于验证队列），他们在 2007 年至 2018 年期间接受了恩替卡韦/替诺福韦治疗超过 12 个月。使用多变量 Cox 模型的预测因子建立了 HCC 风险预测模型，并进行了自举验证。
推导队列和验证队列的 10 年累积 HCC 发生率分别为 12.6%和 13.7%。NFM 早期反应的 HCC 风险显著不同，12 个月时 NFM 显著下降的患者 HCC 风险明显降低（P < 0.001）。NFM 反应、性别、年龄和肝硬化是 HCC 的独立预测因子。我们根据每个变量的回归系数开发了基于纤维化标志物反应、性别、年龄和肝硬化（FSAC）的评分。对于 HCC 的 10 年预测，FSAC 的 C 指数值高于 PAGE-B、改良 PAGE-B、CU-HCC 和 REACH-B（分别为 0.84 与 0.77、0.80、0.77 和 0.67；所有 P < 0.005）。在验证队列中，FSAC 的预测性能也得到了证实，C 指数值高于其他模型（所有 P < 0.050）。
NFM 的治疗中变化是 HCC 风险的独立指标。包含 NFM 反应的 FSAC 是 HCC 风险评估的可靠风险评分，性能优于其他模型。
