核苷（酸）类似物抗病毒治疗对乙型肝炎病毒相关性肝癌病理分化及预后的影响

Effect of nucleos （t）ide analog antiviral treatment on the pathological differentiation and prognosis of hepatitis B virus-related hepatocellular carcinoma

目的探讨核苷（酸）类似物抗病毒治疗对HBV相关性肝癌病理分化的影响及肝癌预后的影响因素。方法回顾性分析2007年3月至2013年11月哈尔滨医科大学附属第一医院HBV相关性肝癌且行肝部分切除的患者127例。其中术前接受核苷（酸）类似物治疗16例，术前未抗病毒治疗111例，分析两组之间病理分化的差异。术后抗病毒及术后未抗病毒患者分别为29例和82例，随访并分析两组间术后生存及复发的情况，应用多因素分析肝癌预后的影响因素。计数资料比较采用卡方检验或Fisher确切概率法，生存率的比较采用Log-rank秩检验，生存的影响因素采用单因素、多因素Cox回归模型。结果术前抗病毒治疗患者高、中、低分化肝细胞癌所占比例分别为18．75％、68．75％和12．50％，术前未抗病毒治疗患者分别为16．22％、66．67％和17．11％，差异无统计学意义（x2=0．224，P=0．885）。127例患者的总体中位生存时间为39个月，6个月、1年、2年的生存率分别为91．7％、77．5％、59．3％。术后抗病毒治疗患者的6个月、1年、2年生存率分别为96．3％、92．4％、78．5％，明显高于术后未抗病毒治疗患者的85．9％、70．0％、48．5％，差异有统计学意义（x2=6．967，P=0．008）。单因素分析显示，肿瘤大小、肿瘤数目、门静脉转移、甲胎蛋白（AFP）水平、术后抗病毒治疗、病理分化、TNM分级、巴塞罗那临床分期（BCLC分期）、γ-GT、PTA是肝癌术后生存的影响因素（均P〈0．05）。多因素分析显示，AFP水平（HR=1，95％CI：1．000441．002，P=0．004）、术后抗病毒治疗（HR=0．38，95％CI：0．38～0．15，P=0．04）和BCLC分期（C比A：HR=3．63，95％CI：1．31～10．09，P=0．04）是影响肝癌患者生存的独立预测因素。结论核苷（酸）类似物抗病毒治疗对HBV相关性肝癌的病理分化无显著影响，而AFP水平、BCLC分期和术后抗病毒治疗是影响肝癌术后生存的独立预测因素。

Objective To explore the effect of nucleos（t）ide analog （NA） antiviral treatment on the pathological differentiation of hepatitis B virus （HBV）-related hepatocellular carcinoma （HCC） and the prognostic factors of HCC. Methods Totally 127 patients with HBV-related HCC who were hospitalized and received partial hepatectomy in First Affiliated Hospital of Harbin Medical University from March 2007 to November 2013 were included in this study. Sixteen cases received antiviral treatment before operation and the remaining 111 cases had no history of NA treatment. The differences of histopathological grading were compared between the two groups. Twenty-nine patients received antiviral treatment for the first time after surgery, and the rest 82 patients did not. All these patients were followed up for survival and recurrence. Multivariate analysis was used to explore the prognostic factors for HCC. The categorical variables were analyzed by X2 test or Fisher exact test. Survival rate was compared with Log-rank test. Univariate or multivariate Cox regression analysis was used to explore the related factors of survival. Results The proportions of well-, moderately- or poorly-differentiated HCC in patients with antiviral treatment before surgery were 18.75 %, 68.75 % and 12.5%, respectively. Whereas the proportions in those without treatment were 16. 22%, 66. 67% and 17. 11%, respectively. There was no significant difference in histopathological grading of HCC between the two groups （x2= 0. 224, P= 0. 885）. The overall median survival time was 39 months. The 6-month, 1- and 2-year survival rates were 91. 7%, 77.5% and 59.3%, respectively. The f-month, 1- and 2-year survival rate of postoperative antiviral treatment were 96.3%, 92.4% and 78.5%, respectively, which were significantly higher than those of no antiviral treatment group （85. 9%, 70. 0% and 48. 5%, respectively; x2 =6. 967, P=0. 008）. Univariate analysis showed that tumor number, size, portal vein transfer, AFP level, postoperative antiviral treatment, histopathological grading, TNM staging, BCLC staging, γ-GT and PTA were prognostic factors for postoperative HCC survival. Multivariate analysis showed that AFP level （HR= 1, 95%CI： 1. 0004--1. 002, P=0. 004）, postoperative antiviral treatment （HR=0. 38, 95%CI： 0.38- 0.15, P=0.04） andBCLC stage （Bvs A： HR=1. 55, 95%CI： 0.76 -3.18; CvsA： HR=3.63, 95% CI; 1.31-10.09, P = 0.04） were independent prognostic factors. Conclusions Preoperative antiviral treatment has no impact on the histopathological grading of HCC. BCLC stage, AFP level and postoperative antiviral treatment are independent prognostic factors for HBV-related HCC.