目的 观察恩替卡韦(entecavir,ETV)单用及联合使用聚乙二醇干扰素(peginterferon,Peg-IFN)治疗高病毒载量慢性乙型肝炎(chronic hepatitis B,CHB)患者的疗效.方法 该项前瞻性非随机队列研究纳入了2019年12月至2023年12月在南昌大学第一附属医院等4家医院接受治疗的152例高病毒载量CHB患者.根据治疗方案将患者分为ETV组102例及Peg-IFN与ETV联合治疗组50例.主要结局指标为48周时乙型肝炎病毒(hepatitis B virus,HBV)表面抗原(hepatitis B virus s antigens,HBsAg)血清清除率.次要结局指标为48周HBsAg下降水平、HBV e抗原(hepatitis B virus e antigens,HBeAg)血清清除率、HBV-DNA阴转率及下降水平以及ALT下降水平.计量资料符合正态分布,两组间比较采用独立样本t检验,治疗前后组内比较采用重复测量方差分析.计数资料两组间比较采用卡方检验,治疗前后组内比较采用Cochran's Q检验多重比较进行统计分析.结果 两组患者的ALT、HBV-DNA和HBsAg水平在整个48周治疗期间较治疗前均显著下降(P＜0.001).治疗48周时,ETV组丙氨酸氨基转移酶(30.82±9.86)U/L显著低于联合治疗组(37.57±19.84)U/L(P=0.027);ETV组HBV-DNA和HBsAg水平分别为(1.22±1.17)lg IU/mL和(3.65±0.85)lg IU/mL均显著高于联合治疗组(0.82±0.96)lg IU/mL和(2.62±1.45)lg IU/mL(P=0.034,P＜0.001).ETV组治疗48周时HBeAg和HBV-DNA清除率较治疗前均显著升高(P＜0.001),而HBsAg清除率与治疗前差异无统计学意义(P=0.171).联合治疗组治疗48周时HBsAg、HBeAg和HBV-DNA清除率较治疗前均显著升高(P＜0.05).治疗48周时,ETV组HBsAg和HBeAg血清清除率分别2.0％和13.7％均显著低于联合治疗组12.0％和38.0％(P=0.027,P=0.001);ETV组HBV-DNA清除率89.2％低于联合治疗组94.0％,差异无统计学意义(P=0.509).结论 Peg-IFN联合ETV治疗方案可作为高病毒载量CHB患者的首选治疗方案.
Efficacy of Entecavir Alone and in Combination with Peginterferon in the Treatment of Patients with High Viral Load Chronic Hepatitis B
Objective To observe the efficacy of entecavir(ETV)alone and in combination with peginterferon(Peg-IFN)in the treatment of patients with high viral load chronic hepatitis B(CHB).Methods This prospective cohort study included 152 patients with high viral load CHB who were treated at four hospitals,including the First Affiliated Hospital of Nanchang University,between December 2019 and December 2023.Based on the patients'conditions and their own wishes,the patients were divided into the ETV group(n=102)and the Peg-IFN and ETV combined treatment group(n=50).The primary endpoint was defined as HBV surface antigen(HBsAg)seroclearance at week 48.Secondary endpoints were the 48-week HBsAg decline level,HBV e antigen(HBeAg)seroclearance,HBV-DNA negative conversion rate and decline level,and ALT decline level.Measurement data conformed to normal distribution and were compared between two groups using two independent samples t-test,and within-group comparisons before and after treatment were analyzed using repeated measures ANOVA.Count data were compared between two groups using the chi-square test,and within-group comparisons before and after treatment were statistically analyzed using Cochran's Q test for mul-tiple comparisons.Results ALT,HBV-DNA,and HBsAg levels decreased significantly in both groups throughout the 48-week treat-ment period compared with pre-treatment(P＜0.001).At 48 weeks of treatment,alanine aminotransferase(30.82±9.86)U/L was significantly lower in the ETV group than in the combination therapy group(37.57±19.84)U/L(P=0.027);The HBV-DNA and HBsAg levels in the ETV group were significantly higher at(1.22±1.17)lg IU/mL and(3.65±0.85)lg IU/mL,respectively,than those in the combination therapy group at(0.82±0.96)lg IU/mL and(2.62±1.45)lg IU/mL(P=0.034,P＜0.001).Both HBeAg and HBV-DNA clearance were significantly higher in the ETV group at 48 weeks of treatment compared with pre-treatment(P＜0.001),whereas the difference between HBsAg clearance and pre-treatment was not statistically significant(P=0.171).HBsAg,HBeAg,and HBV-DNA clearance rates were significantly higher in the combination therapy group at 48 weeks of treatment compared to pre-treatment(P＜0.05).At 48 weeks of treatment,HBsAg and HBeAg seroclearance rates of 2.0％and 13.7％,respectively,were significantly lower in the ETV group than in the combination therapy group at 12.0％and 38.0％(P=0.027,P=0.001);The HBV-DNA clearance rate of 89.2％in the ETV group was lower than that of 94.0％in the combination therapy group,but the difference was not statistically significant(P=0.509).Conclusion The Peg-IFN combined with ETV regimen can be the first recommended treatment option for patients with high viral load CHB.
万方数据
维普
