Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
School of Medicine, China Medical University, Taichung, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
J Formos Med Assoc. 2022 Mar;121(3):703-711. doi: 10.1016/j.jfma.2021.08.003. Epub 2021 Aug 25.
The risk of hepatocellular carcinoma (HCC) is reduced but not eliminated after nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB). We aimed to investigate the role of serum Prothrombin Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) and alpha-fetoprotein in predicting HCC and mortality in cirrhotic CHB patients at virological remission (VR) following NA therapy.
Patients with CHB-related cirrhosis undergoing NA therapy from two medical centers in Taiwan were retrospectively included. Serum PIVKA-II were quantified by an automated chemiluminescence assay. Multivariable Cox proportional hazards regression models were used to identify predictors for HCC and death. Serial on-treatment PIVKA-II levels after VR were investigated.
Overall, 293 CHB-related cirrhosis patients were included. At VR, the mean age was 55, and the mean PIVKA-II level was 35 mAU/mL. After a mean follow-up of 78 months, 76 patients developed HCC and 19 died. After adjustment for confounding factors, alpha-fetoprotein >7 ng/mL (hazard ratio [HR]: 2.84, 95% confidence interval [CI]: 1.73-4.67) and PIVKA-II >50 mAU/mL (HR: 2.46, 95%CI: 1.35-4.49) at VR significantly predicted HCC development. In patients with alpha-fetoprotein ≤10 ng/mL or ≤20 ng/mL at VR, PIVKA-II >50 mAU/mL increased 2.45 or 3.16-fold risk of HCC, respectively. PIVKA-II levels after VR increased serially in patients who developed HCC afterwards.
In patients with CHB-related cirrhosis, serum alpha-fetoprotein >7 ng/mL and PIVKA-II >50 mAU/mL at the time of antiviral therapy-induced VR is associated with a greater risk of HCC. PIVKA-II is a predictive marker for HCC in patients with low normal alpha-fetoprotein level.
核苷（酸）类似物（NA）治疗慢性乙型肝炎（CHB）后，肝细胞癌（HCC）的风险降低但并未消除。我们旨在研究血清 Prothrombin Induced by Vitamin K Absence or Antagonist-II（PIVKA-II）和甲胎蛋白在抗病毒治疗诱导的病毒学应答（VR）后 NA 治疗的 CHB 相关肝硬化患者中的作用，以预测 HCC 和死亡率。
回顾性纳入来自台湾两家医疗中心的 CHB 相关肝硬化接受 NA 治疗的患者。通过自动化学发光测定法定量检测血清 PIVKA-II。使用多变量 Cox 比例风险回归模型确定 HCC 和死亡的预测因素。研究 VR 后治疗过程中连续的 PIVKA-II 水平。
总体而言，纳入了 293 例 CHB 相关肝硬化患者。在 VR 时，平均年龄为 55 岁，平均 PIVKA-II 水平为 35 mAU/mL。平均随访 78 个月后，76 例患者发生 HCC，19 例患者死亡。调整混杂因素后，VR 时甲胎蛋白>7ng/mL（危险比 [HR]：2.84，95%置信区间 [CI]：1.73-4.67）和 PIVKA-II>50 mAU/mL（HR：2.46，95%CI：1.35-4.49）显著预测 HCC 发生。在 VR 时甲胎蛋白≤10ng/mL 或≤20ng/mL 的患者中，PIVKA-II>50 mAU/mL 分别使 HCC 的风险增加 2.45 倍或 3.16 倍。随后发生 HCC 的患者 VR 后 PIVKA-II 水平连续升高。
在 CHB 相关肝硬化患者中，抗病毒治疗诱导的 VR 时血清甲胎蛋白>7ng/mL 和 PIVKA-II>50 mAU/mL 与 HCC 风险增加相关。PIVKA-II 是甲胎蛋白水平正常低值患者 HCC 的预测标志物。
