核苷(酸)类似物抗病毒治疗HBV相关肝细胞癌患者低病毒血症及其对肿瘤治疗疗效的影响

Impact of low-level viremia on prognosis in patients with hepatitis B virus-related hepatocellular carcinoma after TACE therapy

目的分析核苷(酸)类似物(NAs)抗病毒治疗乙型肝炎病毒(HBV)相关肝细胞癌(HCC)患者发生低病毒血症(LLV)及其对肿瘤治疗疗效的影响。方法2016年1月~2020年12月我院收治的HBV相关HCC初治患者119例,所有患者均接受肝动脉化疗栓塞术(TACE)及其综合抗肿瘤治疗,给予恩替卡韦(ETV)或富马酸替诺福韦二吡呋酯抗病毒治疗。随访截止时间为2021年12月31日。结果在119例HBV相关HCC患者中,有42例(35.3%)抗病毒后发生LLV;LLV组血清HBeAg阳性率为64.3%,显著高于非LLV组的27.3%(P<0.05);在治疗后3个月,LLV组肿瘤客观缓解率(ORR)为33.3%,显著低于非LLV组的58.4%(P<0.05);在治疗后6个月,LLV组血清ALT、AST、Child-Pugh评分和甲胎蛋白(AFP)水平分别为35.0(28.6,56.0)U/L、56.0(43.6,78.5)U/L、7.0(6.0,8.0)分和2732.0(85.7,17595.0)ng/ml,显著高于非LLV组【分别为29.0(21.0,43.0)U/L、40.0(27.0,61.0)U/L、6.0(5.0,7.0)分和22.5(5.2,780.6)ng/ml,P<0.05】;LLV组2 a生存率为2.4%,显著低于非LLV组的41.6%(P<0.05);Logistic回归分析显示,是否存在LLV【HR(95%CI)为2.1(1.3~3.3)】、巴塞罗那(BCLC)分期【HR(95%CI)为1.7(1.2~1.9)】和射频消融术(RFA)【HR(95%CI)为0.4(0.2~0.7)】是影响HBV相关HCC患者预后的独立因素(P<0.05)。结论HBeAg阳性可能是HBV相关HCC患者NAs治疗后发生LLV的影响因素,而LLV可能影响抗肿瘤治疗疗效,值得重视。

Objective The aim of this study was to investigate the impact of low-level viremia(LLV)on prognosis in patients with hepatitis B virus-related hepatocellular carcinoma(HCC)after transarterial chemoembolization(TACE)therapy.Methods 119 patients with HBV-related HCC were admitted to our hospital between January 2016 and December 2020,and all patients received comprehensive anti-tumor therapy based on TACE and nucleoside(acid)analogs(NAs)for antiviral therapy.All patients were followed-up to December 31,2021.Results Among the 119 patients,42(35.3%)had LLV after antiviral therapy;serum HBeAg positive rate in patients with LLV was 64.3%,significantly higher than that in the non-LLV group(27.3%,P<0.05);at the end of 3 months after TACE treatment,the ORR in patients with LLV was significantly lower than that in the non-LLV group(33.3%vs.58.4%,P<0.05);6 months after treatment,serum ALT,AST,Child-Pugh score and AFP levels in patients with LLV were 35.0(28.6,56.0)U/L,56.0(43.6,78.5)U/L,7.0(6.0,8.0)and 2732.0(85.7,17595.0)ng/ml,significantly higher than[29.0(21.0,43.0)U/L,40.0(27.0,61.0)U/L,6.0(5.0,7.0)and 22.5(5.2,780.6)ng/ml,respectively,P<0.05]in the non-LLV group;the 2-year survival in patients with LLV was 2.4%,significantly lower than 41.6%(P<0.05)in the non-LLV group;the multivariate Logistic analysis showed that with or without LLV[HR(95%CI):2.1(1.3-3.3)],Barcelona Clinic Liver Cancer(BCLC)stage[HR(95%CI):1.7(1.2-1.9)]and radiofrequency ablation[HR(95%CI):0.4(0.2-0.7)]were the independent prognostic factors for patients with HBV-related HCC(P<0.05).Conclusion Serum HBeAg positive might influence antiviral response to NAs therapy,and the LLV might impact the prognosis of patients with HBV-related HCC after TACE treatment,which warrants concerns clinically.