Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
Liver Int. 2018 Nov;38(11):1997-2005. doi: 10.1111/liv.13889. Epub 2018 Jun 12.
BACKGROUND & AIMS: This study investigates the long-term incidences and predictors of developing hepatocellular carcinoma (HCC), cirrhotic events and mortality in cirrhotic patients receiving entecavir (ETV) therapy.
We enrolled 481 nucleos(t)ide analogue-naïve chronic hepatitis B (CHB) patients who had compensated cirrhosis upon entry and had received ETV monotherapy for >12 months.
The 8-year cumulative incidences of developing HCC, cirrhotic events and liver-related mortality were 26.5%, 8.62% and 10.03% respectively. Multivariate analysis revealed that diabetic mellitus (DM), higher fibrosis-4 (FIB-4) and alpha-foetoprotein (AFP) levels at 12 months of treatment, and FIB-4 increase from baseline to 12 months were independent factors of HCC. FIB-4 and AFP levels at 12 months of treatment were also independent factors of cirrhotic events and mortality. FIB-4 cut-off values of 3, 3 and 5 as well as AFP cut-offs of 5, 5, and 9 ng/mL at 12 months of treatment were optimal for predicting HCC, cirrhotic events and mortality during therapy respectively. The FIB-4 and AFP levels at 12 months of treatment were assessed for the combined risk of developing clinical outcomes. The 8-year incidences of HCC, cirrhotic events and liver-related mortality in the subgroups with low FIB-4 and AFP levels were only 5.95%, 1.03% and 2.43% respectively. DM was an independent predictor of HCC and mortality.
The combination of FIB-4 and AFP levels at 12 months of treatment is a useful marker for predicting the development of HCC, cirrhotic events and mortality in compensated cirrhotic patients with CHB who are receiving ETV therapy.
本研究旨在探讨长期接受恩替卡韦（ETV）治疗的代偿性肝硬化慢性乙型肝炎（CHB）患者发生肝细胞癌（HCC）、肝硬化事件和死亡的发生率及预测因素。
我们纳入了 481 例核苷（酸）类似物初治的 CHB 患者，这些患者在入组时已经患有代偿性肝硬化，并且接受 ETV 单药治疗>12 个月。
8 年的 HCC、肝硬化事件和与肝脏相关的死亡率的累积发生率分别为 26.5%、8.62%和 10.03%。多变量分析显示，治疗 12 个月时的糖尿病（DM）、较高的纤维化-4（FIB-4）和甲胎蛋白（AFP）水平，以及从基线到 12 个月时 FIB-4 的增加是 HCC 的独立因素。治疗 12 个月时的 FIB-4 和 AFP 水平也是肝硬化事件和死亡率的独立因素。治疗 12 个月时 FIB-4 的截断值为 3、3 和 5，AFP 的截断值为 5、5 和 9 ng/mL，是预测治疗期间 HCC、肝硬化事件和死亡率的最佳值。治疗 12 个月时的 FIB-4 和 AFP 水平用于评估发生临床结局的联合风险。在 FIB-4 和 AFP 水平较低的亚组中，HCC、肝硬化事件和与肝脏相关的死亡率的 8 年发生率分别仅为 5.95%、1.03%和 2.43%。DM 是 HCC 和死亡率的独立预测因素。
在接受 ETV 治疗的 CHB 代偿性肝硬化患者中，治疗 12 个月时 FIB-4 和 AFP 水平的联合是预测 HCC、肝硬化事件和死亡率发生的有用标志物。
