恩替卡韦联合甘草酸二铵肠溶胶囊治疗慢性乙型病毒性肝炎的临床研究

Clinical trial of entecavir combined with diammonium glycyrrhetinate enteric-coated capsules in the treatment of patients with chronic viral hepatitis B

目的 研究恩替卡韦联合甘草酸二铵肠溶胶囊治疗慢性乙型病毒性肝炎(CHB)的疗效及安全性。方法 将CHB患者随机分为试验组和对照组。试验组患者给予恩替卡韦联合甘草酸二铵肠溶胶囊,恩替卡韦,每次0.5 mg,每天1次,口服;甘草酸二铵肠溶胶囊,前10周每次150 mg,每天3次,第11周每次100 mg,每天3次,第12周每次50 mg,每天3次,口服,持续服药12周。对照组患者给予恩替卡韦,每次0.5 mg,每天1次,口服,持续服药12周。治疗后,比较2组患者的临床疗效、乙型病毒性肝炎病毒(HBV)-DNA水平和乙型病毒性肝炎表面抗原(HBsAg)阳性率、肝功能、临床恢复情况、肝纤维化指标、炎症因子水平和药物不良反应发生情况。结果 试验组和对照组,各36例。试验组和对照组的临床总有效率分别为为94.45%和80.55%,差异有统计学意义(P<0.05)。治疗后,试验组和对照组的HBV-DNA水平分别为(180±120)和(1 250±830)cps·mL^(-1),HBsAg阳性率分别为6.7%和36.7%,TBIL分别为(34.75±5.49)和(58.91±6.33)μmol·L^(-1),谷草转氨酶(GOT)分别为(52.33±8.81)和(73.48±10.38)U·L^(-1),谷丙转氨酶(GPT)分别为(50.41±6.43)和(86.32±9.26)U·L^(-1),PTA分别为(86.70±12.18)%和(67.73±9.79)%,差异均有统计学意义(均P<0.05)。试验组和对照组的肝功能指标恢复时间分别为(3.06±0.78)和(4.32±1.01)周;病毒转阴时间分别为(3.03±0.81)和(4.29±0.96)周,差异有统计学意义(P<0.05)。治疗后,2组患者血清Ⅲ型前胶原肽(PC-Ⅲ)、Ⅳ型胶原(Ⅳ-C)、透明质酸(HA)和层粘连蛋白(LN)水平均低于治疗前,且试验组PC-Ⅲ、Ⅳ-C、HA和LN水平均低于对照组(均P<0.05)。试验组和对照组的药物不良反应总发生率分别为11.11%和16.67%,差异无统计学意义(P>0.05)。结论 恩替卡韦联合甘草酸二铵肠溶胶囊治疗CHB临床疗效较好,可改善肝功能,延缓肝纤维化进展,降低炎症反应,且无明显药物不良反应发生,安全性高。

Objective To study the efficacy and safety of entecavir combined with diammonium glycyrrhizinate enteric-coated capsule in the treatment of chronic viral hepatitis B(CHB).Methods Patients with CHB were randomly divided into treatment group and control group.Treatment group was given entecavir combined with diammonium glycyrrhizinate enteric-coated capsule,entecavir orally,0.5 mg each time,once a day;capsules of diammonium glycyrrhizinate enteric-coated were taken orally,150 mg each time,3 times a day for the first 10 weeks,100 mg each time,3 times a day for the 11th week,50 mg each time,3 times a day for the 12th week,for 12 weeks.Control group was given entecavir orally,0.5 mg once a day for 12th weeks.After treatment,the clinical efficacy,HBV-DNA level,positive rate of hepatitis B virus surface antigen(HBsAg),liver function,clinical recovery,liver fibrosis index,inflammatory factor level and occurrence of adverse drug reactions were compared between the two groups.Results There were 36 cases in treatment group and 36 cases in control group.The total clinical effective rate in treatment group and control group were 94.45%and 80.55%,the difference was statistically significant(P<0.05).After treatment,hepatitis B virus(HBV)-DNA levels in treatment group and control group were(180±120)and(1250±8.30)cps·mL^(-1);the positive rate of HBsAg were 6.7%and 36.7%;TBIL were(34.75±5.49)and(58.91±6.33)μmol·L^(-1);glutamic-0xaloacetic transaminase(GOT)were(52.33±8.81)and(73.48±10.38)U.L^(-1);glutamic-pyruvic transaminase(GPT)were(50.41±6.43)and(86.32±9.26)U.L^(-1);PTA values were(86.70±12.18)%and(67.73±9.79)%,the differences were statistically significant(all P<0.05).The recovery time of liver function indexes in treatment group and control group were(3.06±0.78)and(4.32±1.01)weeks;the time of virus turning negative were(3.03±0.81)and(4.29±0.96)weeks,the difference was statistically significant(P<0.05).After treatment,the serum levels of type II procollagen peptide(PC-II),type IV collagen(IV-C),hyaluronic acid(HA)and laminin(LN)in two groups were lower than before treatment,and the levels of PC-II,IV-C,HA and LN in treatment group were lower than those in control group(all P<0.05).The total incidence of adverse drug reactions in treatment group and control group were 11.11%and 16.67%,with no statistical significance(P>0.05).Conclusion Entecavir combined with diammonium glycyrhizate enteric-coated capsules has good clinical efficacy in the treatment of CHB,can improve liver function,delay the progression of liver fibrosis,reduce the inflammatory response,and no significant adverse drug reactions,with high safety.