Liu Xiufeng, Zhuang Lijun, Yang Fan, Liu Ping, Xia Zhaojun, Guo Ying, Dong Pingping, Chen Chao, Li Zixiong
Department of Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.
Department of Nephrology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, People's Republic of China.
J Hepatocell Carcinoma. 2025 Jun 27;12:1241-1252. doi: 10.2147/JHC.S527332. eCollection 2025.
AFP positivity (≥20 ng/mL) is often used as one of the diagnostic criteria for HCC. The aim of this study is to analyze the prognosis of advanced HCC with negative (<20 ng/mL) AFP at baseline following systemic drug treatment.
In this study, 91 patients with AFP-negative advanced HCC who received systemic drug treatment in Nanjing Jinling Hospital from February 2011 to September 2023 were collected, and 213 patients with AFP-positive advanced HCC were collected as the control group. A propensity score model was used to adjust for potential confounding variables. Cox regression analysis was used to clarify the differences of prognosis in subgroups for HCC patients.
Following propensity score matching with 1:2 ratio, 90 HCC patients from Group A (AFP-negative) and 180 from Group B (AFP-positive) were chosen to participate in the final analysis set. The OS of AFP-negative HCC patients was extended by 13.5 months compared to AFP-positive HCC patients. Within the AFP-negative HCC group, the top-ranked first-line treatment options were TKIs combo ICIs (mPFS = 9.5m, mOS = 37.1m), chemotherapy combo ICIs (mPFS = 8.1m, mOS = 15.5m), and TKIs (mPFS = 5.6m, mOS = 28.2m). Subgroup analysis indicated that among AFP-negative HCC patients, those without PVTT or with HBV DNA <50lU/mL had longer survival time. For HCC patients who opted for TKIs combo ICIs as their first-line treatment and then switched to TKIs alone for second-line treatment, the mOS and 95% CI were 30.7 (24.8-NA) months.
The survival time of AFP-negative HCC patients was significantly longer than that of AFP positive HCC patients. Patients with no PVTT or HBV DNA <50lU/mL have relatively better efficacy of systemic drug therapy. With the AFP-negative HCC patients, TKIs combo ICIs are preferentially recommended for the first-line therapy, and TKIs are used for the second-line therapy after progression.
甲胎蛋白阳性（≥20 ng/mL）常被用作肝癌的诊断标准之一。本研究旨在分析全身药物治疗后基线甲胎蛋白阴性（<20 ng/mL）的晚期肝癌患者的预后情况。
本研究收集了2011年2月至2023年9月在南京金陵医院接受全身药物治疗的91例甲胎蛋白阴性晚期肝癌患者，并收集了213例甲胎蛋白阳性晚期肝癌患者作为对照组。采用倾向评分模型对潜在混杂变量进行调整。采用Cox回归分析来阐明肝癌患者亚组预后的差异。
按1:2的比例进行倾向评分匹配后，从A组（甲胎蛋白阴性）选择90例肝癌患者，从B组（甲胎蛋白阳性）选择180例患者纳入最终分析集。与甲胎蛋白阳性肝癌患者相比，甲胎蛋白阴性肝癌患者的总生存期延长了13.5个月。在甲胎蛋白阴性肝癌组中，排名靠前的一线治疗方案是酪氨酸激酶抑制剂联合免疫检查点抑制剂（中位无进展生存期=9.5个月，中位总生存期=37.1个月）、化疗联合免疫检查点抑制剂（中位无进展生存期=8.1个月，中位总生存期=15.5个月）和酪氨酸激酶抑制剂（中位无进展生存期=5.6个月，中位总生存期=28.2个月）。亚组分析表明，在甲胎蛋白阴性肝癌患者中，无门静脉癌栓或乙肝病毒DNA<50 lU/mL的患者生存时间更长。对于选择酪氨酸激酶抑制剂联合免疫检查点抑制剂作为一线治疗，然后转为单独使用酪氨酸激酶抑制剂进行二线治疗的肝癌患者，中位总生存期及95%置信区间为30.7（24.8-无上限）个月。
甲胎蛋白阴性肝癌患者的生存时间显著长于甲胎蛋白阳性肝癌患者。无门静脉癌栓或乙肝病毒DNA<50 lU/mL的患者全身药物治疗疗效相对较好。对于甲胎蛋白阴性肝癌患者，一线治疗优先推荐酪氨酸激酶抑制剂联合免疫检查点抑制剂，进展后二线治疗使用酪氨酸激酶抑制剂。
