Serum growth differentiation factor 15 predicts hepatocellular carcinoma occurrence after hepatitis C virus elimination
Serum growth differentiation factor 15 predicts hepatocellular carcinoma occurrence after hepatitis C virus elimination
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DOI：
10.1111/apt.16691
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发表时间：
2021-11-23
影响因子：
7.6
通讯作者：
Takehara, Tetsuo
中科院分区：
文献类型：
--
作者：
Myojin, Yuta;Hikita, Hayato;Takehara, Tetsuo
背景：丙型肝炎病毒（HCV）清除后，由于肝细胞癌（HCC）的风险，患者应进行随访。生长分化因子15（GDF 15）是一种由线粒体功能障碍或氧化应激诱导的细胞因子，目的探讨GDF 15对HCV清除后HCC发生的预测价值。方法：我们检测了经直接作用抗病毒药物（DAA）治疗后获得持续病毒学应答的无HCC病史的慢性HCV感染患者血清中GDF 15水平。结果：在推导队列中，DAA治疗后发生HCC的患者血清GDF 15水平高于未发生HCC的患者。多变量考克斯比例风险分析显示基线GDF 15（>1350 pg/mL，HR 2.54）、AFP（>5 ng/mL，HR 2.00）和FIB-4指数（>3.25，HR 2.69）是HCC的独立风险因素。基于GDF 15、AFP和FIB-4指数的评分对HCC发生风险进行分层。在验证队列中，低评分组（N = 171）、中评分组（N = 300）和高分组（N = 166）3年时的累积HCC发生率分别为0.64%、3.27%和15.3%。在整个队列中，用FIB-4指数将患者分为
Background: After hepatitis C virus (HCV) elimination, patients should be followed up due to risk of hepatocellular carcinoma (HCC). Growth differentiation factor 15 (GDF15) is a cytokine induced by mitochondrial dysfunction or oxidative stress.AimTo evaluate the prognostic value of GDF15 for HCC occurrence after HCV elimination.Methods: We measured GDF15 levels in stored serum from patients with chronic HCV infection without a history of HCC who had achieved sustained virological response with direct-acting antiviral agents (DAAs). The patients were randomly divided into derivation (n = 964) and validation (n = 642) cohorts.Results: In the derivation cohort, serum GDF15 levels were higher in those with HCC occurrence after DAA treatment than in those without. Multivariate Cox proportional hazards analysis revealed baseline GDF15 (>1350 pg/mL, HR 2.54), AFP (>5 ng/mL, HR 2.00), and the FIB-4 index (>3.25, HR 2.69) to be independent risk factors for HCC. Scoring based on GDF15, AFP and the FIB-4 index stratified HCC occurrence risk. In the validation cohort, the cumulative HCC occurrence rate at 3 years was 0.64%, 3.27% and 15.3% in low-score (N = 171), medium-score (N = 300) and high-score (N = 166) groups, respectively. In the total cohort, scoring divided patients with a FIB-4 index