Department of Pancreatic Hepatobiliary Surgery, The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou 510655, Guangdong Province, China.
Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
World J Gastroenterol. 2023 Feb 28;29(8):1359-1373. doi: 10.3748/wjg.v29.i8.1359.
Serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) is a promising biomarker for hepatocellular carcinoma (HCC) surveillance.
To identify the contributing factors related to the abnormal elevation of PIVKA-II level and assess their potential influence on the performance of PIVKA-II in detecting HCC.
This study retrospectively enrolled in 784 chronic liver disease (CLD) patients and 267 HCC patients in Mengchao Hepatobiliary Hospital of Fujian Medical University from April 2016 to December 2019. Logistic regression and the area under the receiver operating characteristic curve (AUC) were used to evaluate the influencing factors and diagnostic performance of PIVKA-II for HCC, respectively.
Elevated PIVKA-II levels were independently positively associated with alcohol-related liver disease, serum alkaline phosphatase (ALP), and total bilirubin (TBIL) for CLD patients and aspartate aminotransferase (AST) and tumor size for HCC patients (all < 0.05). Serum PIVKA-II were significantly lower in patients with viral etiology, ALP ≤ 1 × upper limit of normal (ULN), TBIL ≤ 1 × ULN, and AST ≤ 1 × ULN than in those with nonviral disease and abnormal ALP, TBIL, or AST (all < 0.05), but the differences disappeared in patients with early-stage HCC. For patients with TBIL ≤ 1 × ULN, the AUC of PIVKA-II was significantly higher compared to that in patients with TBIL > 1 × ULN (0.817 0.669, = 0.015), while the difference between ALP ≤ 1 × ULN and ALP > 1 × ULN was not statistically significant (0.783 0.729, = 0.398). These trends were then more prominently perceived in subgroups of patients with viral etiology and HBV alone.
Serum PIVKA-II has better performance in detecting HCC at an early stage for CLD patients with normal serum TBIL.
维生素 K 缺乏或拮抗剂-II(PIVKA-II)诱导的血清蛋白是肝细胞癌(HCC)监测的一种很有前途的生物标志物。
确定与 PIVKA-II 水平异常升高相关的因素,并评估它们对 PIVKA-II 检测 HCC 性能的潜在影响。
本研究回顾性纳入 2016 年 4 月至 2019 年 12 月福建医科大学孟超肝胆医院的 784 例慢性肝病(CLD)患者和 267 例 HCC 患者。使用逻辑回归和受试者工作特征曲线(ROC)下面积(AUC)分别评估 PIVKA-II 对 HCC 的影响因素和诊断性能。
升高的 PIVKA-II 水平与 CLD 患者的酒精性肝病、血清碱性磷酸酶(ALP)和总胆红素(TBIL)以及 HCC 患者的天门冬氨酸氨基转移酶(AST)和肿瘤大小呈独立正相关(均<0.05)。与非病毒性疾病和异常 ALP、TBIL 或 AST 患者相比,病毒性病因、ALP≤1×正常值上限(ULN)、TBIL≤1×ULN 和 AST≤1×ULN 的患者血清 PIVKA-II 显著降低(均<0.05),但在早期 HCC 患者中差异消失。对于 TBIL≤1×ULN 的患者,PIVKA-II 的 AUC 明显高于 TBIL>1×ULN 的患者(0.817比 0.669,=0.015),而 ALP≤1×ULN 与 ALP>1×ULN 之间的差异无统计学意义(0.783比 0.729,=0.398)。这些趋势在病毒性病因和仅 HBV 的患者亚组中更为明显。
对于 TBIL 正常的 CLD 患者,血清 PIVKA-II 在早期检测 HCC 时具有更好的性能。