乙肝相关性肝细胞癌患者术后早期复发与晚期复发影响因素分析

Influencing factors of early and late recurrence of HBV-related hepatocellular carcinoma after operation

目的观察乙肝相关性肝细胞癌患者根治性切除术后早期及晚期复发情况,探讨术后早期及晚期复发的危险因素。方法150例乙肝相关性肝细胞癌患者均行根治性肝切除术,术后组织病理提示微血管侵犯(microvascular invasion,MVI)分级M1或M2级者于术后1个月行经导管肝动脉化疗栓塞治疗,术前和/或术后给予抗乙肝病毒治疗。根据术后随访结果,将患者分为早期复发组(术后1年内复发)、晚期复发组(术后≥1年复发)、未复发组。比较早期复发组与未复发组、晚期复发组与未复发组术前甲胎蛋白(α-fetoprotein,AFP)、异常凝血酶原(prothrombin induced by vitamin K absence or antagonist-Ⅱ,PIVKA-Ⅱ)、谷丙转氨酶、谷草转氨酶、谷氨酰转移酶、总胆红素、白蛋白水平,白蛋白-胆红素分级,巴塞罗那分期,HBV-DNA载量,乙型肝炎E抗原(hepatitis B virus e antigen,HBeAg)阳性、肝硬化、肉眼血管侵犯率,肿瘤直径,肿瘤个数,MVI分级;采用Cox比例风险模型分析乙肝相关性肝细胞癌患者术后早期及晚期复发的危险因素。结果150例中21例行半肝以上切除术,122例行肝叶或肝段切除,7例行局部切除术;82例术后1个月左右行经导管肝动脉化疗栓塞术。中位随访时间29.5个月,未复发79例,早期复发48例,晚期复发23例。早期复发组年龄≤55岁、肿瘤数目≥2个、肿瘤直径>5 cm、MVI分级M2级、巴塞罗那分期B~C期、谷氨酰转移酶>60 u/L、AFP≥20μg/L、PIVKA-Ⅱ≥40 mAu/mL、HBeAg阳性、AFP≥20μg/L+PIVKA-Ⅱ≥40 mAu/mL比率均高于未复发组(P<0.05)。晚期复发组肿瘤数目≥2个、HBeAg阳性比率均高于未复发组(P<0.05)。肿瘤数目≥2个(HR=2.044,95%CI:1.081~3.863,P=0.028)、MVI分级M2级(HR=3.081,95%CI:1.440~6.593,P=0.004),AFP≥20μg/L且PIVKA-Ⅱ≥40 mAU/mL(HR=2.591,95%CI:1.121~5.430,P=0.028)是乙肝相关性肝细胞癌患者术后早期复发的危险因素;肿瘤数目≥2个(HR=3.267,95%CI:1.761~6.060,P=0.001),HBeAg阳性(HR=2.734,95%CI:1.494~5.000,P=0.001)是乙肝相关性肝细胞癌患者术后晚期复发的危险因素。结论乙肝相关性肝细胞癌患者肿瘤数目≥2个、MVI分级M2级、术前AFP和PIVKA-Ⅱ同时升高者更易出现早期复发,肿瘤数目≥2个、术前HBeAg阳性者术后易出现晚期复发。

Objective To observe the early and late recurrence of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after radical hepatectomy,and to investigate the risk factors of early and late recurrence.Methods In 150 patients with HBV-HCC undergoing radical hepatectomy,those with postoperative histopathological microvascular invasion(MVI)grade M1 or M2 received transcatheter hepatic arterial chemoembolization 1 month after operation,and anti-hepatitis B virus therapy was given before and/or after operation.During postoperative follow-up,150 patients were divided into early recurrence group(recurrence 1 year after operation),late recurrence group(recurrence≥1 year after operation)and no-recurrence group.The preoperativeα-fetoprotein(AFP),prothrombin induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ),glutamic-pyruvic transaminase,glutamic-oxaloacetic transaminase,glutamyl-transferase,total bilirubin,albumin,albumin-bilirubin score grade,Barcelona Clinic Liver Cancer stage,HBV-DNA load,percentages of patients with hepatitis B virus e antigen(HBeAg)positive,liver cirrhosis and gross vascular invasion,tumor diameter,number of tumors,and MVI grade were compared between early recurrence group and no-recurrence group and between late recurrence group and no-recurrence group.Cox proportional risk model was used to analyze the risk factors of early and late recurrence in patients with HBV-HCC.Results In 150 patients,21 patients underwent hemihepatectomy,122 patients underwent liver lobe or segment resection,7 patients underwent local resection,and 82 patients underwent transcatheter hepatic arterial chemoembolization about 1 month after operation.The follow-up lasted 29.5 months averagely,showing no recurrence in 79 patients,early recurrence in 48 and late recurrence in 23.The percentages of patients with age≤55 years,≥2 tumors,>5 cm in tumor diameter,M2 MVI grade,B-C Barcelona Clinic Liver Cancer stage,glutamyl-transferase>60 u/L,AFP≥20μg/L,PIVKA-Ⅱ≥40 mAu/mL,HBeAg positive,and AFP≥20μg/L+PIVKA-Ⅱ≥40 mAu/mL were higher in early recurrence group than those in no-recurrence group(P<0.05).The percentages of patients with≥2tumors and HBeAg positive were higher in late recurrence group than those in no-recurrence group(P<0.05).Tumors≥2(HR=2.044,95%CI:1.081-3.863,P=0.028),M2MVI grade(HR=3.081,95%CI:1.440-6.593,P=0.004),and AFP≥20μg/L+PIVKA-Ⅱ≥40 mAU/mL(HR=2.591,95%CI:1.121-5.430,P=0.028)were the risk factors of early recurrence in patients with HBV-HCC,while tumors≥2(HR=3.267,95%CI:1.761-6.060,P=0.001)and HBeAg positive(HR=2.734,95%CI:1.494-5.000,P=0.001)were the risk factors of late recurrence.Conclusion The HBV-HCC patients with≥2tumors,M2 MVI grade,and preoperative elevated AFP and PIVKA-Ⅱlevels are more likely to have early recurrence,while the patients with≥2tumors and preoperative HBeAg positive are more likely to have late recurrence.