原发性肝癌微波消融术后对血清高尔基体蛋白73、甲胎蛋白的影响

摘要/Abstract

摘要： 目的观察原发性肝癌(PLC)微波消融(MWA)疗效及对血清高尔基体蛋白73(GP73)和甲胎蛋白(AFP)的影响。方法收集2016年01月—2018年10月在第九一〇医院住院治疗的单个病灶直径≤ 3 cm且AFP升高的PLC 102例,所有患者均接受MWA治疗,观察治疗前后血清GP73、AFP及生化学指标[白蛋白(Alb)、总胆红素(TBil)、丙氨酸氨基转移酶(ALT)和天冬氨酸氨基转移酶(AST)]变化;随访3年以上,通过增强MRI或增强CT评估MWA疗效。结果 MWA术后1个月97例(95.10%)PLC达到完全消融,MWA术后1、2、3年总生存率分别为100.00%、97.06%和89.22%。MWA术后3年累积复发47例(46.08%),其中局部肿瘤进展9例(8.82%),新发肿瘤38例(37.25%)。MWA术后1年、2年和3年无病生存率分别为74.51%、58.82%和53.92%。MWA术后1周、2周和4周AFP持续下降,显著低于治疗前水平(P值均<0.001)。MWA治疗后12周AFP恢复正常水平。相反,血清GP73水平在MWA术后1周和2周显著升高,术后2周达到高峰值,经保肝治疗后血清GP73在MWA术后4周明显下降,MWA术后12周恢复到治疗前水平。生化学指标TBil、ALT和AST在MWA术后1周均显著升高,MWA术后引起血清GP73变化与生化学指标(TBil、ALT和AST)的变化相似。结论肝癌MWA术后血清GP73含量显著升高,因而,血清GP73有可能作为监测和评估PLC患者MWA诱导肝脏炎症损伤的潜在生物标志物。AFP可作为MWA疗效评估和复发的监测指标,AFP正常化与PLC完全消融密切相关。

关键词: 原发性肝癌, 微波消融, 高尔基体蛋白73, 甲胎蛋白

Abstract: Objective To observe the efficacy of microwave ablation (MWA) in the treatment of primary liver cancer (PLC) and its effect on serum levels of Golgi protein 73 (GP73) and alpha fetoprotein (AFP).Methods A total of 102 PLC patients with a single small lesion (≤ 3 cm in diameter) and elevated AFP were retrospectively enrolled between January 2016 and October 2018. All of the PLC patients received MWA. Serum GP73, alpha-fetoprotein (AFP), and liver biochemical tests [serum albumin (Alb), total bilirubin (TBil), alanine aminotransferase (ALT), and aspartate aminotransferase (AST)] were compared before MWA and at different time points post the ablation procedure. The efficacy of MWA was evaluated by enhanced MRI or CT follow-up for more than 3 years.Results Complete tumor ablation was achieved in 97 patients (95.10%) with PLC at one month after MWA. The overall survival rates of 1, 2 and 3 years after MWA were 100.00%, 97.06% and 89.22%, respectively. In terms of PLC recurrence, cumulative recurrence occurred in 47 cases (46.08%) at 3 years after MWA, including 9 cases (8.82%) with local tumor progression and 38 cases (37.25%) with new tumors. The disease-free survival rates at 1, 2 and 3 years after MWA were 74.51%, 58.82% and 53.92%, respectively. The serum AFP levels significantly decreased at 1, 2, and 4 weeks after MWA, and returned to the normal range at 12 weeks after MWA. On the contrary, the serum GP73 level increased significantly at 1 and 2 weeks after MWA, and reached the peak at 2 weeks after MWA. After hepato-protective treatment, the serum GP73 declined at 4 weeks after MWA, and returned to the pre-treatment level at 12 weeks after MWA. Liver biochemical indicators of TBil, ALT, and AST were increased significantly at 1 week after MWA. Notably, the changes of serum GP73 in response to MWA were similar to those of liver biochemical indicators (TBil, ALT and AST).Conclusion Serum GP73 increased significantly after MWA treatment for PLC. Therefore, serum GP73 holds potential as a biomarker for monitoring and assessment of MWA-mediated inflammatory injury in patients with PLC. AFP can be used as a monitoring index to evaluate the treatment efficacy of MWA and HCC recurrence after MWA. The normalization of AFP is closely associated with a complete tumor ablation.

Key words: Primary liver cancer, Microwave ablation, Golgi protein 73, Alpha fetoprotein

许正锯, 刘会国, 颜燕燕, 叶巧霞, 张小曼, 黄进发, 李勇飞, 吴金票. 原发性肝癌微波消融术后对血清高尔基体蛋白73、甲胎蛋白的影响[J]. 肝脏, 2023, 28(5): 554-558.

XU Zheng-ju, LIU Hui-guo, YAN Yan-yan, YE Qiao-xia, ZHANG Xiao-man, HUANG Jin-fa, LI Yong-fei, WU Jin-piao. Effect of microwave ablation on serum levels of Golgi protein 73 and alpha fetoprotein in patients with primary liver cancer[J]. Chinese Hepatolgy, 2023, 28(5): 554-558.

参考文献

[1] Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 2021, 71(3):209-249.
[2] Fung J, Lai CL, Yuen MF. Hepatitis B and C virus-related carcinogenesis. Clin Microbiol Infect, 2009,15(11):964-970.
[3] Neuveut C, Wei Y, Buendia MA. Mechanisms of HBV-related hepatocarcinogenesis. J Hepatol, 2010, 52(4):594-604.
[4] Hasegawa K, Aoki T, Ishizawa T, et al. Comparison of the therapeutic outcomes between surgical resection and percutaneous ablation for small hepatocellular carcinoma. Ann Surg Oncol, 2014, 21 Suppl 3:S348-355.
[5] Liang P, Yu J, Lu MD, et al. Practice guidelines for ultrasound-guided percutaneous microwave ablation for hepatic malignancy. World J Gastroenterol, 2013, 19(33):5430-5438.
[6] Shibata T, Iimuro Y, Yamamoto Y, et al. Small hepatocellular carcinoma: comparison of radio-frequency ablation and percutaneous microwave coagulation therapy. Radiology, 2002, 223(2):331-337.
[7] Vogl TJ, Nour-Eldin NA, Hammerstingl RM, et al. Microwave Ablation (MWA): Basics, Technique and Results in Primary and Metastatic Liver Neoplasms - Review Article. Rofo, 2017, 189(11):1055-1066.
[8] Shiina S, Sato K, Tateishi R, et al. Percutaneous Ablation for Hepatocellular Carcinoma: Comparison of Various Ablation Techniques and Surgery. Can J Gastroenterol Hepatol, 2018, 2018:4756147.
[9] Zhou H, Sun Y, Wang Q, et al. N-acetylcysteine alleviates liver injury by suppressing macrophage-mediated inflammatory response post microwave ablation. Int Immunopharmacol, 2020, 85:106580.
[10] Kladney RD, Bulla GA, Guo L, et al. GP73, a novel Golgi-localized protein upregulated by viral infection. Gene, 2000, 249(1-2):53-65.
[11] Liu X, Wan X, Li Z, et al. Golgi protein 73(GP73), a useful serum marker in liver diseases. Clin Chem Lab Med, 2011, 49: 1311-1316.
[12] Xu Z, Shen J, Pan X, et al. Predictive value of serum Golgi protein 73 for prominent hepatic necroinflammation in chronic HBV infection. J Med Virol,2018, 90(6):1053-1062.
[13] Xu Z, Liu L, Pan X, et al. Serum Golgi protein 73 (GP73) is a diagnostic and prognostic marker of chronic HBV liver disease. Medicine (Baltimore),2015, 94(12): e659.
[14] Aghoram R, Cai P, Dickinson JA. Alpha-foetoprotein and/or liver ultrasonography for screening of hepatocellular carcinoma in patients with chronic hepatitis B. Cochrane Database Syst Rev, 2012, 2012(9):CD002799.
[15] Yao M, Zhao J, Lu F. Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma. Oncotarget, 2016, 7(4):3702-3708.
[16] Harris PS, Hansen RM, Gray ME, et al. Hepatocellular carcinoma surveillance: An evidence-based approach. World J Gastroenterol, 2019, 25(13):1550-1559.
[17] 中华人民共和国国家卫生健康委员会医政医管局. 原发性肝癌诊疗规范(2019年版). 中华肝脏病杂志, 2020, 28(2):112-128.
[18] 中华医学会感染病学分会, 中华医学会肝病学分会. 慢性乙型肝炎防治指南(2019年版). 肝脏, 2019, 24(12): 1335-1356.
[19] Luo W, Zhang Y, He G, et al. Effects of radiofrequency ablation versus other ablating techniques on hepatocellular carcinomas: a systematic review and meta-analysis. World J Surg Oncol, 2017, 15(1):126.
[20] Poulou LS, Botsa E, Thanou I, et al. Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma. World J Hepatol. 2015, 7(8):1054-1063.
[21] Ierardi AM, Giorlando F, Piacentino F, et al. Factors predicting outcomes of microwave ablation of small hepatocellular carcinoma. Radiol Med, 2017, 122(2):81-87.
[22] Poggi G, Tosoratti N, Montagna B, et al. Microwave ablation of hepatocellular carcinoma. World J Hepatol, 2015, 7(25):2578-2589.
[23] Bhardwaj N, Dormer J, Ahmad F, et al. Microwave ablation of the liver: a description of lesion evolution over time and an investigation of the heat sink effect. Pathology, 2011, 43(7):725-731.
[24] Wang ZL, Liang P, Dong BW, et al. Prognostic factors and recurrence of small hepatocellular carcinoma after hepatic resection or microwave ablation: a retrospective study. J Gastrointest Surg, 2008, 12(2):327-337.
[25] Rao Z, Ling W, Dai X, et al. Precoagulation with microwave ablation for hepatic parenchymal transection during liver partial resection. Int J Hyperthermia, 2019, 36(1):146-150.
[26] Zhang M, Ma H, Zhang J, et al. Comparison of microwave ablation and hepatic resection for hepatocellular carcinoma: a meta-analysis. Onco Targets Ther, 2017, 10:4829-4839.
[27] Zhang EL, Yang F, Wu ZB, et al. Therapeutic efficacy of percutaneous microwave coagulation versus liver resection for single hepatocellular carcinoma ≤3 cm with Child-Pugh A cirrhosis. Eur J Surg Oncol, 2016, 42(5):690-697.
[28] 中华医学会检验医学分会分子诊断学组. 肝细胞癌生物标志物检测及应用专家共识. 国际检验医学杂志, 2020, 41(24):2945-2948.