Departments of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Center for Translational Research, The Institute of Medical Science Hospital, The University of Tokyo, Tokyo, Japan.
J Gastroenterol. 2018 Jul;53(7):883-889. doi: 10.1007/s00535-017-1424-0. Epub 2017 Dec 29.
Nucleot(s)ide analogues (NA) can reduce the risk of hepatocellular carcinoma (HCC), but not completely prevent its development.
Two hundred and thirty-four chronic hepatitis B patients virologically well controlled with entecavir or tenofovir disoproxil fumarate for more than 1 year were enrolled in this study. Over the median observation period of 51 (12-142) months, 24 of 234 patients developed HCC. We quantified HBV markers, alpha-fetoprotein (AFP) and Mac-2-binding protein glycosylation isomer (M2BPGi) at baseline and 48 weeks after therapy.
Serum AFP and M2BPGi tended to decline from baseline to 48 weeks after treatment both in patients who did and those who did not develop HCC. Univariate Cox regression analysis indicated that serum M2BPGi levels ≥ 1.215 COI at 48 weeks were associated with HCC development [hazard ratio (HR) 5.73; p ≤ 0.001]. Multivariate analysis showed that male sex (HR 5.6; p = 0.01), AFP ≥ 9.65 ng/ml (HR 22.01; p ≤ 0.001), M2BPGi ≥ 1.215 (HR 5.07; p = 0.004) at 48 weeks were significant independent predictive factors for HCC development. Based on a scoring system consisting of three factors above described, Kaplan-Meier analysis for four groups (score 0, 1, 2, ≥ 3), revealed significant differences in cumulative HCC occurrence for each group within 2 years. The rate of incidence of HCC was 0, 5.4, 23.4, and 75% in each group, respectively.
In patients receiving NA therapy, higher M2BPGi at 48 weeks, as well as male sex and higher AFP at 48 weeks were independent risk factors for HCC development.
核苷（酸）类似物（NA）可以降低肝细胞癌（HCC）的风险，但不能完全预防其发生。
本研究纳入了 234 例慢性乙型肝炎患者，他们在接受恩替卡韦或替诺福韦酯治疗 1 年以上后病毒学得到了很好的控制。在中位观察期为 51（12-142）个月期间，234 例患者中有 24 例发生 HCC。我们在基线和治疗后 48 周时定量检测了 HBV 标志物、甲胎蛋白（AFP）和 Mac-2 结合蛋白糖基化异构体（M2BPGi）。
血清 AFP 和 M2BPGi 在发生 HCC 和未发生 HCC 的患者中，从基线到治疗后 48 周均呈下降趋势。单因素 Cox 回归分析表明，治疗后 48 周时血清 M2BPGi 水平≥1.215 COI 与 HCC 发生相关[风险比（HR）5.73；p≤0.001]。多因素分析显示，男性（HR 5.6；p=0.01）、AFP≥9.65ng/ml（HR 22.01；p≤0.001）和 M2BPGi≥1.215（HR 5.07；p=0.004）是 HCC 发生的独立预测因素。基于包含上述三个因素的评分系统，Kaplan-Meier 分析四组（评分 0、1、2、≥3），发现每组在 2 年内 HCC 累积发生率有显著差异。每组 HCC 发生率分别为 0、5.4%、23.4%和 75%。
在接受 NA 治疗的患者中，治疗后 48 周时 M2BPGi 水平升高，以及男性和 AFP 水平升高是 HCC 发生的独立危险因素。
