乙型肝炎病毒DNA载量对晚期肝细胞癌系统治疗安全性及预后的影响

Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma

目的观察乙型肝炎(乙肝)病毒(HBV)阳性对接受系统治疗的晚期肝细胞癌(肝癌)患者发生肝损害、HBV再激活(HBVr)及HBVr对系统治疗预后的影响。方法回顾性收集2018年7月至2020年12月中山大学附属第三医院等4家医院403例乙肝相关肝癌患者的临床资料,分析系统治疗期间肝损害及HBVr发生率,并分析HBVr对生存预后的影响。结果共纳入403例患者,359例(89.1%)为男性,年龄(51.5±12.1)岁。进行倾向性评分匹配(PSM)前,高HBV-DNA(基线HBV-DNA>1000 U/ml,n=147)组与低HBV-DNA(基线HBV DNA≤1000 U/ml,n=256)组相比,肝硬化、TNM及巴塞罗那分期(BCLC)晚期患者比例较高(P<0.05)。进行PSM后基线指标在两组间差异无统计学意义。高HBV-DNA组和低HBV-DNA组在肝损害和HBVr发生率上差异均无统计学意义(均P>0.05)。对169例有生存数据的患者进行生存分析,发现高HBV-DNA组和低HBV-DNA组的中位总生存期(OS)分别为11.49个月(95%CI:7.77~12.89)和16.65个月(95%CI:10.54~21.99,P=0.008),中位无进展生存期(PFS)分别为7.41个月(95%CI:5.06~8.67)和10.55个月(95%CI:6.72~13.54,P=0.038),差异均有统计学意义,但有无HBVr、有无肝损害的患者OS和PFS差异均无统计学意义(均P>0.05)。结论系统治疗前HBV-DNA>1000 U/ml并不增加乙肝相关肝癌患者系统治疗时肝损害或HBVr的风险,该类患者可以安全地接受系统治疗。

Objective To study the effect of hepatitis B virus(HBV)infection on the occurrence of liver damage,HBV reactivation(HBVr)and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma(HCC)receiving systemic therapy.Methods The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases,The Third Affiliated Hospital of Sun Yat-Sen University et al,from July 2018 to December 2020 were collected.The incidence of liver damage and HBVr during systematic therapy,and the influence of HBVr on survival prognosis were analyzed.Results Of the 403 patients,89.1%were male(n=359),with a median age of 51 years(51.5±12.1).Before propensity score matching(PSM),the proportion of patients with cirrhosis,TNM and advanced BCLC stage was higher in high HBV-DNA(baseline HBV-DNA>1000 U/ml,n=147)group comparing with the low HBV-DNA(baseline HBV DNA≤1000 u/ml,n=256)group(P<0.05).There was no significant difference in baseline indexes between the two groups after PSM.In 290 patients after PSM,there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group(P>0.05).Survival analysis was performed on 169 patients with survival data,the median overall survival(OS)was found to be 11.49 months(95%CI:7.77-12.89)and 16.65 months(95%CI:10.54-21.99,P=0.008)in the high and low HBV-DNA groups,respectively.And median progression-free survival(PFS)was 7.41 months(95%CI:5.06-8.67)and 10.55 months(95%CI:6.72-13.54,P=0.038),respectively,with a statistically significant difference.There were no differences in overall survival(OS)and progression-free survival(PFS)between patients with and without HBVr and those with or without liver damage(P>0.05).Conclusions HBV-DNA levels above 1000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma,and such patients can safely receive systemic therapy.