恩替卡韦单药与联合干扰素抗病毒治疗对慢性乙型肝炎患者肝细胞癌发生风险的影响

Abstract

摘要:

目的探究恩替卡韦 (ETV) 联合干扰素 (IFN) 治疗与ETV单药治疗对慢性乙型肝炎相关肝细胞癌 (HCC) 发生的影响。方法回顾性选取2008年1月-2014年12月在北京地坛医院收治的409例慢性乙型肝炎患者,根据抗病毒治疗方式不同分为联合IFN组 (n=169,IFN治疗≥6个月) 及ETV单药组 (n=240,ETV治疗≥12个月) ,随访截止至2019年6月,以观察对象发生HCC为终点事件。连续变量两组间比较采用Mann-Whitney U检验,分类变量两组间比较采用χ2检验。倾向评分匹配法 (PSM) 消除组间基线差异,Kaplan-Meier法及log-rank检验用于比较组间的HCC发生率,Cox比例风险回归模型分析影响HCC发生的危险因素。结果研究中位随访时间为5.4 (4.9～7.9) 年。联合IFN组HCC累积发病率与ETV单药组相比,匹配前后差异均无统计学意义 (PSM前:1.2%vs 2.8%,χ2=1.423,P=0.233; PSM后:1.7%vs 4.1%,χ2=1.676,P=0.195) ;亚组分析表明,在非高风险患癌人群中两组HCC累积发病率也无明显差异 (1.3%vs 1.5...

Alternate abstract:

Objective To investigate the effect of entecavir( ETV) alone or combined with interferon( IFN) on the risk of hepatocellular carcinoma( HCC) in patients with chronic hepatitis B( CHB). Methods A retrospective analysis was performed for 409 patients with CHB who were admitted to Beijing Ditan Hospital from January 2008 to December 2014,and according to their antiviral therapy,they were divided into ETV + IFN group with 169 patients( IFN treatment for ≥6 months) and ETV group with 240 patients( ETV treatment for ≥12 months). The patients were followed up to June 2019,and the development of HCC was the outcome event. The Mann-Whitney U test was used for comparison of continuous variables between two groups,and the chi-square test was used for comparison of categorical variables between two groups. The propensity score matching( PSM) method was used to eliminate baseline differences between groups,the Kaplan-Meier method and the log-rank test were used to compare the incidence rate of HCC between groups,and the Cox proportional-hazards regression model analysis was used to investigate the risk factors for the development of HCC. Results The median follow-up time in this study was 5. 4 years( IQR: 4. 9-7. 9). There was no significant difference in the cumulative incidence rate of HCC between the two groups before and after PSM( before PSM: 1. 2% vs 2. 8%,χ2= 1. 423,P = 0. 233; after PSM: 1. 7% vs 4. 1%,χ2= 1. 676,P = 0. 195),and the subgroup analysis also showed no significant difference in the cumulative incidence rate of HCC between the two groups in the non-high risk population( 1. 3% vs 1. 5%,χ2= 0. 335,P = 0. 563). The Cox proportional-hazards regression model showed that age was an independent risk factor for HCC( hazard ratio = 1. 107,95% confidence interval: 1. 005-1. 219,P = 0. 038). Conclusion For CHB patients without a high risk of cancer,compared with ETV monotherapy,ETV combined with IFN for at least 6 months does not significantly reduce the risk of HCC.