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经动脉化疗栓塞术单用及联合靶向药物治疗中期肝癌的肝功能变化及预后比较OACSTPCD

Liver function changes and prognosis of intermediate hepatocellular carcinoma patients treated with transcatheter arterial chemoembolization(TACE)versus TACE plus targeted medicine

中文摘要英文摘要

背景 经动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)和酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)是原发性肝细胞癌(hepatocellular carcinoma,HCC)治疗的常用手段,然而关于TACE与TACE-TKI对中期HCC术后肝功能的影响及预后差异的临床研究仍缺乏.目的 比较TACE与TACE-TKI(索拉非尼或仑伐替尼)治疗中期HCC的短期肝功能变化、并发症、生存情况[无进展生存期(progression free survival,PFS)]及其关联因素.方法 收集2010年 6月—2023年 1月规律就诊于解放军总医院第五医学中心肝脏肿瘤科的中期HCC患者 149例,依据治疗方法将其分为TACE组和TACE-TKI组,研究随访至 2023年 6月,对首次TACE治疗前、治疗后 48 h、治疗后 2个月的肝功能、术后并发症及生存预后进行分析.结果 149例患者中,TACE组 97例,TACE-TKI组 52例(索拉非尼组 27例,仑伐替尼组25例).两组基线特征差异无统计学意义(P>0.05).术后 48 h TACE-TKI组肝功能不全占比高于TACE组(42.3%vs 21.6%,P=0.008);白细胞、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素均较术前升高(P<0.05),而血小板、白蛋白均较术前下降(P<0.05),但组间差异无统计学意义.术后 2个月TACE-TKI组总胆红素水平高于TACE组(19.1 μmol/L vs 14.4 μmol/L,P=0.001),差异有统计学意义.TACE-TKI组的术后并发症占比高于TACE组(30.7%vs 15.5%,P<0.05).中位随访时间为 6.08年,TACE组PFS优于TACE-TKI组(47个月vs 32个月,P<0.05).Cox回归分析显示,甲胎蛋白≤647 ng/mL(HR=0.570,95%CI:0.357~0.909,P=0.018)、天冬氨酸氨基转移酶≤31 μ/L(HR=0.527,95%CI:0.319~0.872,P=0.013)、凝血酶原活动度≤93%(HR=0.507,95%CI:0.310~0.832,P=0.007)、TACE次数>2次(HR=2.104,95%CI:1.359~3.259,P=0.001)、单用TACE治疗方案(HR=0.598,95%CI:0.380~0.942,P=0.027)患者的PFS更长.结论 相比于TACE,TACE-TKI治疗中期肝细胞癌时,发生肝功能不全和术后并发症的概率更高.对于接受TACE或TACE-TKI治疗的中期肝细胞癌患者,甲胎蛋白>647 ng/mL、TACE次数≤2次、天冬氨酸氨基转移酶>31 μ/L、凝血酶原活动度>93%、使用TACE-TKI方案在一定范围内与更差的PFS存在相关性.

Background Transcatheter arterial chemoembolization(TACE)and tyrosine kinase inhibitors(TKI)are usually used in treatment of hepatocellular carcinoma(HCC).However,there is a lack of clinical studies examining the influence of TACE and TACE-TKI on postoperative liver function and prognosis in intermediate HCC.Objective To compare the short-term changes in liver function,complications,and survival outcomes(progression-free survival,PFS)associated with TACE and TACE-TKI(Sorafenib or Lenvatinib)treatments for intermediate HCC and identify their associated factors.Methods The medical records of 149 patients with intermediate HCC who underwent TACE or TACE-TKI in the Fifth Medical Center of Chinese PLA General Hospital were collected from June 2010 to January 2023.According to different therapies,patients were divided into TACE group and TACE-TKI group.The PFS was followed up to June 2023.Liver function before TACE,48 h and 2 months after TACE,complications and survival outcomes were compared between the two groups.Results The baseline characteristics were not significantly different between TACE group(n=97)and TACE-TKI group(n=52).The percentage of hepatic dysfunction was higher in the TACE-TKI group than that in the TACE group at 48 h after TACE(42.3%vs 21.6%,P=0.008).At 48 h after TACE,white blood cell count(WBC),alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total bilirubin(TBIL)in the two groups were all higher than those before TACE(P<0.05),while the levels of platelet(PLT)and albumin(ALB)in both groups were lower compared with those before TACE(P<0.05).At 2 months after TACE,TBIL was higher in the TACE-TKI group than that in the TACE group(19.1 μmol/L vs 14.4 μmol/L,P=0.001).The TACE-TKI group had a higher incidence of postoperative complications than that of the TACE group(30.7%vs 15.5%,P<0.05).The median follow-up time was 6.08 years.PFS was longer in the TACE group than that in the TACE-TKI group(47 months vs 32 months,P<0.05).Multivariate Cox analysis showed that Alpha fetoprotein(AFP)≤647 ng/mL(HR=0.570,95%CI:0.357-0.909,P=0.018),AST≤31 μ/L(HR=0.527,95%CI:0.319-0.872,P=0.013),prothrombin activity(PTA)≤93%(HR=0.507,95%CI:0.310-0.832,P=0.007),TACE treatment>twice(HR=2.104,95%CI:1.359-3.259,P=0.001)and the TACE therapy(HR=0.598,95%CI:0.380-0.942,P=0.027)were associated with longer PFS.Conclusion TACE-TKI(Sorafenib or Lenvatinib)group has a higher occurrence of liver dysfunction and postoperative complications than that of the TACE group during the treatment of intermediate HCC.AFP>647 ng/mL,TACE treatment≤twice,AST>31 μ/L,the TACE-TKI therapy and PTA>93%may be associated with worse PFS in intermediate HCC patients treated with TACE or TACE-TKI.

王沫萱;程家敏;千年松

解放军医学院,北京 100853||解放军总医院第八医学中心呼吸与危重症医学部胸部肿瘤科,北京 100091解放军总医院第五医学中心肝病医学部肝病科,北京 100039解放军总医院第八医学中心呼吸与危重症医学部胸部肿瘤科,北京 100091

临床医学

中期肝细胞癌经动脉化疗栓塞术索拉非尼仑伐替尼肝功能术后并发症

intermediate hepatocellular carcinomatranscatheter arterial chemoembolizationsorafeniblenvatinibliver functionpostoperative complications

《解放军医学院学报》 2024 (003)

230-238 / 9

科技青年培育计划(2019NPY112);海南省重点研发项目(ZDYF2023SHFZ117)

10.12435/j.issn.2095-5227.2024.009

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