肝癌患者不同剂量化疗药物经导管动脉化疗栓塞后肝功能的变化

Changes of liver function after transcatheter arterial chemoembolization with use of different dose of anticancer drugs in hepatocellular carcinoma

目的:探讨肝癌患者经导管肝动脉栓塞术(TACE)中化疗药物用量对肝功能的影响. 方法:112例肝癌患者随机分为两组行选择性TACE,A组(n=52)给予小剂量化疗药物:肿瘤瘤径小于5 cm者给予丝裂霉素(MMC)2-4mg;在5-8cm之间者给予MMC 4-6mg, 表阿霉素(EPI)10 mg;大于8 cm者给予MMC 6-8 mg, EPI 10 mg,卡铂(CBP)100 mg;B组(n=60)给予常规剂量化疗药物(丝裂霉素10 mg,卡铂300 mg,表阿霉素40mg). 经导管向供血动脉内注入碘油-化疗药物乳化剂,随后用明胶海绵粒或聚乙烯醇(PVA)微球栓塞供血动脉.TACE术前、术后3d、1 wk、4 wk分别行肝功能检查,比较总胆红素(TBIL)、白蛋白(ALB)、谷丙转氨酶(ALT)及Child-Pugh 评分的变化情况. 结果:两组术前各指标(Child评分、TBIL、ALT、ALB) 均无显著差异(f值分别为0.722、0.962、0.725和0.872, P均>0.05).A组术后3 d,Child评分、TBIL、ALT均显著升高(t值分别为5.319、6.707、7.355,P均<0.01). A组术后1 wk,Child评分、TBIL、ALT与术前比较有显著差异(t值分别为2.243、4.774、2.568,P分别<0.05, P<0.01和P<0.05).A组术后3 d和1 wk,ALB较术前显著下降(t为2.704和7.120,P均<0.01).术后4 wk, A组所有参数均与术前没有显著差异(t值分别为1.890、0.167、0.396和1.273,P均>0.05):B组术后3 d和1 wk, Child评分、TBIL、ALT和ALB与术前相比均显著差异(t值分别为8.859、8.203、9.820、3.463和4.645、6.774、8.747、9.798,P均<0.01).术后4 wk,B组除ALT与术前没有显著性差异(t=1.596,P>0.05)外, Child-Pugh、TBIL和ALB仍与术前有显著差异(t分别为2.603、2.361、和8.881,P分别<0.05,P<0.05,P<0.01). 结论:HCC超选择TACE中,使用小剂量化疗药物引起短暂的、一过性肝功能损害,而应用常规剂量化疗药物可导致更为持久、严重的肝功能损害.

AIM: To study the damage to liver function after transcatheter arterial chemoembolization (TACE) with use of low-dose and conventional-dose of anticancer drugs in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and twelve patients with unresectable HCC were randomly divided into two groups to receive superselective TACE. Patients in group A (n =52) received low-dose anticancer drugs: 2-4mg mitomycin C (MMC) was used when the tumor was less than 5cm in size, while 4-6 mg MMC and 10 mg epirubicin (EPI) were given if tumors were between 5 cm and 8cm in diameter, and 6-8 mg MMC, 10 mg EPI and 100 mg CBP were employed when tumors were larger than 8 cm. Patients in group B (n =60) were given conventional-dose of anticancer drugs (10 mg MMC, 40 mg EPI and 300 mg CBP). Lipiodol-anticancer-drugs emulsion was injected into the feeding arteries of tumors followed by gelfoam or polyvinyl alcohol (PVA) particles embolization. Liver function was evaluated with Child-Pugh scores, total bilirubin levels (TBIL), albumin (ALB) and alanine aminotransferase (ALT) before TACE, 3 days, one-week and 4 weeks after procedures. RESULTS: There was no significant difference between groups A and B in all baseline parameters (Child-Pugh scores, TBIL, ALT and ALB) before TACE (t =0.722, 0.962, 0.725 and 0.872 respectively,P>0.05). In group A, Child-Pugh scores, TBIL and ALT increased significantly 3 days after TACE (t = 5.319, 6.707 and 7.355 respectively, P<0.01) and significant difference were exhibited between baseline and parameters 1 wk after TACE (t =2.243, 4.774 and 2.568 respectively, P <0.05, P <0.01 and P <0.05 respectively). ALB was found significant decrease 3 days and 1 wk after TACE in group A (t =2.704 and 7.120 respectively, P<0.01). The difference between the parameters obtained 4 weeks after the procedure and baseline parameters was not significant in group A (t =1.890, 0.167, 0.396 and 1.273 respectively, P>0.05). In group B, statistical differences exhibited between the four baseline parameters and those 3 d after TACE (t =8.859, 8.203, 9.820 and 3.463 respectively, P<0.01), and baseline parameters versus those 1 wk after the procedures (t =4.645, 6.774,8.747 and 9.798 respectively, P<0.01). The difference between the parameters (Child-Pugh scores, TBIL, ALB) obtained 4 weeks after TACE and baseline parameters was significant (t=2.603, 2.361, 8.881; P<0.05, P<0.05, P <0.01 respectively), while no significant difference was observed in ALT(t = 1.596, P>0.05). CONCLUSION: Superselective TACE with use of low-dose anticancer drug(s) induces transient impairment to liver function, but it can cause lasting, more serious worsening of liver function with use of conventional-dose of anticancer drugs.