Department of Radiology and Biomedical Imaging, Division of Interventional Radiology, University of California, San Francisco, 505 Parnassus Ave, M-361, San Francisco, CA 94143.
Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, IL.
AJR Am J Roentgenol. 2021 May;216(5):1283-1290. doi: 10.2214/AJR.20.23478. Epub 2021 Mar 11.
The purpose of this study was to identify risk factors for and outcomes of hepatotoxicity after selective chemoembolization of hepatocellular carcinoma. This retrospective study included 182 patients (136 men and 46 women; median age, 63 years [interquartile range, 57-70 years]) who underwent 338 consecutive doxorubicin drug-eluting bead (DEB) chemoembolization procedures between 2011 and 2014. Outcomes were assessed until November 2019. In 97% of procedures, two or fewer segments were targeted. The Barcelona Clinic Liver Cancer (BCLC) stage was 0 or A for 77 procedures (22.8%), B for 75 (22.2%), C for 122 (36.1%), and D for 64 (18.9%). Hepatotoxicity was defined as worsened ascites or encephalopathy or as grade 3 or 4 elevations in liver function test results, creatinine levels, or the international normalized ratio within 30 days. Risk factors were assessed by univariate and multivariable generalized estimating equations. Transplant-free survival was assessed using Cox proportional hazard models. Hepatotoxicity was observed after 84 of 338 procedures (24.9%) performed for 70 of 182 patients (38.5%) and was irreversible for 40 procedures (11.8%). On multivariable analysis, risk factors for irreversible toxicity included Child-Pugh class C liver function (odds ratio [OR], 4.4; 95% CI, 1.0-19.0; = .04), BCLC stage C (OR, 5.0; 95% CI, 1.6-16.0; = .006) or D (OR, 7.4; 95% CI, 2.1-25.5; = .002) disease, TIPS or hepatofugal portal venous flow (OR, 6.3; 95% CI, 2.3-17.0; < .001), and a serum α-fetoprotein level of 200 ng/mL or greater (OR, 2.6; 95% CI, 1.1-6.1; = .03). Irreversible toxicity was associated with reduced transplant-free survival among patients who were ineligible for liver transplant (hazard ratio, 2.5; standard error, 0.42; = .03). Irreversible hepatotoxicity was common after selective chemoembolization in patients with advanced stage disease, an elevated serum α-fetoprotein level, or reduced hepatic portal venous perfusion, and it may hasten death among patients who are ineligible for liver transplant.
本研究旨在确定肝癌选择性化疗栓塞后发生肝毒性的风险因素和结局。这项回顾性研究纳入了 182 例(男 136 例,女 46 例;中位年龄 63 岁[四分位间距 57-70 岁])患者,他们于 2011 年至 2014 年间接受了 338 次连续的多柔比星载药微球(DEB)化疗栓塞术。直至 2019 年 11 月评估了结局。在 97%的手术中,靶向两个或更少的节段。巴塞罗那临床肝癌(BCLC)分期为 0 期或 A 期 77 例(22.8%),B 期 75 例(22.2%),C 期 122 例(36.1%),D 期 64 例(18.9%)。肝毒性定义为腹水恶化或肝性脑病,或肝功能检查、肌酐水平或国际标准化比值在 30 天内升高至 3 级或 4 级。通过单变量和多变量广义估计方程评估风险因素。使用 Cox 比例风险模型评估无肝移植生存。在为 182 例患者中的 70 例(38.5%)进行的 338 次手术中的 84 次(24.9%)中观察到肝毒性,其中 40 次(11.8%)为不可逆性。多变量分析显示,不可逆毒性的风险因素包括 Child-Pugh 肝功能 C 级(比值比[OR],4.4;95%置信区间[CI],1.0-19.0; =.04)、BCLC 分期 C 期(OR,5.0;95%CI,1.6-16.0; =.006)或 D 期(OR,7.4;95%CI,2.1-25.5; =.002)疾病、TIPS 或肝向性门静脉血流(OR,6.3;95%CI,2.3-17.0; <.001),以及血清甲胎蛋白水平≥200ng/mL(OR,2.6;95%CI,1.1-6.1; =.03)。在不符合肝移植条件的患者中,不可逆毒性与无肝移植生存时间缩短有关(风险比,2.5;标准误差,0.42; =.03)。在晚期疾病、血清甲胎蛋白水平升高或肝门静脉灌注减少的患者中,选择性化疗栓塞后常发生不可逆性肝毒性,这可能加速不符合肝移植条件的患者的死亡。