Liu Jian, Zhang Xiaofeng, Lin Jianbo, Dai Chun, Xie Zhihao, Shi Xintong, Zhu Bin, Cui Longjiu, Wu Yeye, Jing Yuanming, Fu Xiaohui, Yu Wenlong, Wang Kui, Li Jun
Department of Hepatic Surgery, the Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
Department of Biliary Surgery, the Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, China.
Int J Cancer. 2025 Mar 15;156(6):1293-1303. doi: 10.1002/ijc.35224. Epub 2024 Oct 25.
Serum hepatitis B core-related antigen (HBcrAg) is considered a surrogate marker of the amount and activity of intrahepatic covalently closed circular DNA. This study aimed to explore the prognostic value of HBcrAg on patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative hepatectomy undergoing antiviral therapy (AVT). Data of 949 consecutive patients with HBV-related HCC undergoing curative resection between 2010 and 2013 were reviewed. Serum HBcrAg levels were measured at surgery (baseline) for all patients and at the time of 2 years postoperatively (on-treatment) for those without recurrence. Primary endpoint was tumor recurrence. High HBcrAg levels are associated with malignant phenotypes. HBcrAg independently affected both recurrence and overall survival (OS) in patients with negative hepatitis B e antigen (HBeAg-, p = .007 and p = .042, respectively) but not in their positive HBeAg (HBeAg+) counterparts (p = .100 and p = .075, respectively). Patients with high baseline HBcrAg had higher late, but not early recurrence rates than those with low baseline HBcrAg levels, regardless of HBeAg status (HBeAg+: p = .307 for early, p = .001 for late; HBeAg-: p = .937 for early, p < .001 for late). On-treatment HBcrAg independently affected late recurrence in patients stratified by both cirrhosis and HBeAg (p < .001 for all). The predictive power of HBcrAg kinetics for late recurrence was better than that of the baseline and on-treatment HBcrAg. High HBcrAg levels during long-term AVT are associated with late recurrence of HCC after hepatectomy. Combining baseline and on-treatment HBcrAg might be valuable in identifying patients at a high risk of relapse and stratifying surveillance strategies postoperatively.
血清乙型肝炎核心相关抗原（HBcrAg）被认为是肝内共价闭合环状DNA数量和活性的替代标志物。本研究旨在探讨HBcrAg对接受抗病毒治疗（AVT）的乙型肝炎病毒（HBV）相关肝细胞癌（HCC）患者行根治性肝切除术后的预后价值。回顾了2010年至2013年间949例连续接受根治性切除的HBV相关HCC患者的数据。所有患者在手术时（基线）测定血清HBcrAg水平，未复发患者在术后2年时（治疗中）测定。主要终点是肿瘤复发。高HBcrAg水平与恶性表型相关。HBcrAg独立影响乙型肝炎e抗原阴性（HBeAg-）患者的复发和总生存期（OS）（分别为p = 0.007和p = 0.042），但对HBeAg阳性（HBeAg+）患者无此影响（分别为p = 0.100和p = 0.075）。无论HBeAg状态如何，基线HBcrAg水平高的患者晚期复发率高于基线HBcrAg水平低的患者，但早期复发率无差异（HBeAg+：早期p = 0.307，晚期p = 0.001；HBeAg-：早期p = 0.937，晚期p < 0.001）。治疗中HBcrAg独立影响按肝硬化和HBeAg分层的患者的晚期复发（所有p < 0.001）。HBcrAg动力学对晚期复发的预测能力优于基线和治疗中HBcrAg。长期AVT期间高HBcrAg水平与肝切除术后HCC的晚期复发相关。结合基线和治疗中HBcrAg可能有助于识别复发高危患者并对术后监测策略进行分层。
