维生素 K 缺乏或拮抗剂-II 和甲胎蛋白诱导的凝血酶原时间，以预测用直接作用抗病毒药物治疗的丙型肝炎相关肝硬化的高加索患者发生肝细胞癌的发展。

Prothrombin induced by vitamin K absence or antagonist-II and alpha foetoprotein to predict development of hepatocellular carcinoma in Caucasian patients with hepatitis C-related cirrhosis treated with direct-acting antiviral agents.

机构信息

Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Clinical Laboratory, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

出版信息

Aliment Pharmacol Ther. 2022 Feb;55(3):350-359. doi: 10.1111/apt.16685. Epub 2021 Nov 5.

DOI:10.1111/apt.16685

PMID:34738664

Abstract

BACKGROUND

Prothrombin induced by vitamin K absence or antagonist-II (PIVKA-II) and alpha fetoprotein (AFP) are biomarkers for hepatocellular carcinoma (HCC). However, their performance in patients with cirrhosis related to hepatitis C virus (HCV) treated with direct-acting antiviral agents (DAA) is unknown.

AIM

To evaluate PIVKA-II and AFP as HCC predictors in DAA-treated patients with HCV-related cirrhosis METHODS: In this single centre study, patients with cirrhosis from chronic HCV infection and with a sustained virological response (SVR) to DAA were tested for PIVKA-II and AFP (Fujirebio, Japan) at the start of DAA treatment (baseline), end of treatment (EOT) and at HCC diagnosis.

RESULTS

We included 400 patients with mean age 65 (24-92); 56% were men. From baseline to EOT, PIVKA-II did not change (35 vs 35 mAU/mL, P = 0.43) while AFP significantly decreased (12 vs 6 ng/mL, P < 0.0001). After 52 (3-66) months from baseline, 34 (8.5%) patients developed de novo HCC; median AFP 9 (2-12 868) ng/mL and PIVKA-II 80 (22-1813) mAU/mL. EOT-PIVKA-II (HR 3.05, P < 0.0001) and AFP (HR 2.77, P = 0.001) independently predicted HCC together with diabetes (HR 6.12, P < 0.001) and GGT (HR 1.01, P = 0.03). The 4-year cumulative probability of HCC was 24% vs 2% in patients with EOT-PIVKA-II > or ≤41 mAU/mL (P < 0.0001), and 26% vs 9% for EOT-AFP > or ≤15 ng/mL (P = 0.02). By combining EOT-PIVKA-II and AFP, the 4-year probabilities of HCC were 3% in patients testing negative for both markers, 18% in patients positive for both, and 38% in patients positive for at least one (P < 0.0001).

CONCLUSIONS

In patients with HCV-related cirrhosis treated with DAA, PIVKA-II and AFP independently predicted HCC, while their combination improved risk stratification.

摘要

背景

维生素 K 缺乏或拮抗剂 II（PIVKA-II）和甲胎蛋白（AFP）诱导的凝血酶原是肝细胞癌（HCC）的生物标志物。然而，它们在接受直接作用抗病毒药物（DAA）治疗的丙型肝炎病毒（HCV）相关肝硬化患者中的表现尚不清楚。

目的

评估 DAA 治疗的 HCV 相关肝硬化患者中 PIVKA-II 和 AFP 作为 HCC 预测因子的作用。

方法

在这项单中心研究中，对接受 DAA 治疗的慢性 HCV 感染引起的肝硬化患者进行 PIVKA-II 和 AFP（Fujirebio，日本）检测，时间为 DAA 治疗开始时（基线）、治疗结束时（EOT）和 HCC 诊断时。

结果

我们纳入了 400 名平均年龄 65 岁（24-92 岁）的患者；56%为男性。从基线到 EOT，PIVKA-II 没有变化（35 与 35 mAU/mL，P = 0.43），而 AFP 显著降低（12 与 6 ng/mL，P < 0.0001）。从基线开始 52 个月（3-66 个月）后，34 名（8.5%）患者新发 HCC；中位 AFP 为 9（2-12868）ng/mL，PIVKA-II 为 80（22-1813）mAU/mL。EOT-PIVKA-II（HR 3.05，P < 0.0001）和 AFP（HR 2.77，P = 0.001）与糖尿病（HR 6.12，P < 0.001）和 GGT（HR 1.01，P = 0.03）一起独立预测 HCC。EOT-PIVKA-II >或≤41 mAU/mL 患者的 4 年 HCC 累积发生率为 24%比 2%（P < 0.0001），EOT-AFP >或≤15 ng/mL 患者的 4 年 HCC 累积发生率为 26%比 9%（P = 0.02）。通过联合 EOT-PIVKA-II 和 AFP，检测结果均为阴性的患者 4 年 HCC 发生率为 3%，均为阳性的患者为 18%，至少有一项阳性的患者为 38%（P < 0.0001）。