丙酚替诺福韦联合PEG-IFNα-2b治疗慢性乙型肝炎患者疗效研究

Combination of tenofovir alafenamide and PEG-IFNα-2b in treatment of patients with chronic hepatitis B

目的探讨丙酚替诺福韦(TAF)联合聚乙二醇干扰素α-2b(PEG-IFNα-2b)治疗慢性乙型肝炎(CHB)患者的疗效。方法2021年3月~2023年3月我院收治的CHB患者122例,被随机分为对照组61例和观察组61例,分别给予TAF或TAF联合PEG-IFNα-2b治疗48 w。采用实时荧光定量PCR法检测血清HBV DNA载量,采用电化学发光法定量检测血清HBeAg和HBsAg水平,采用ELISA法检测血清Toll样受体4(TLR4)和白细胞介素-35(IL-35)水平。结果在治疗24 w末和治疗48 w末,观察组血清HBeAg水平分别为(195.3±36.4)IU/ml和(180.6±25.9)IU/ml,显著低于对照组【分别为(236.1±42.5)IU/ml和(217.5±33.8)IU/ml,P<0.05】,血清HBsAg水平分别为(925.1±226.9)IU/ml和(816.2±175.3)IU/ml,显著低于对照组【分别为(1028.4±251.5)IU/ml和(921.7±226.8)IU/ml,P<0.05】;观察组HBeAg转阴率分别为21.3%和29.5%,显著高于对照组的3.3%和6.6%(P<0.05);观察组血清TLR4水平分别为(68.6±17.4)pg/mL和(41.4±15.9)pg/mL,显著低于对照组【分别为(90.1±20.5)pg/mL和(73.5±18.2)pg/mL,P<0.05】,血清IL-35水平分别为(127.9±25.5)pg/mL和(73.5±18.6)pg/mL,均显著低于对照组【分别为(191.4±30.6)pg/mL和(102.7±26.1)pg/mL,P<0.05】。结论应用TAF联合PEG-IFNα-2b治疗CHB患者具有良好的抗病毒疗效,能提高血清HBeAg转阴率,可能与降低了TLR4和IL-35表达有关,值得进一步研究。

Objective The aim of this study was to investigate antiviral efficacy of tenofovir alafenamide(TAF)and peginterferon interferonα-2b(PEG-IFNα-2b)combination in treatment of patients with chronic hepatitis B(CHB).Methods A total of 122 patients with CHB were enrolled in our hospital between March 2021 and March 2023,and were randomly divided into control(n=61)and observation(n=61)group,receiving TAF or TAF and PEG-IFNα-2b combination for antiviral therapy for 48 weeks.Serum HBV DNA loads were detected by real-time fluorescence quantitative PCR,serum HBeAg and HBsAg levels were assayed by electrochemiluminescence,and serum Toll-like receptor 4(TLR4)and interleukin-35(IL-35)levels were determined by ELISA.Results By end of 24-week and 48 week treatment,serum HBeAg levels in the combination group were(195.3±36.4)IU/ml and(180.6±25.9)IU/ml,both significantly lower than[(236.1±42.5)IU/ml and(217.5±33.8)IU/ml,P<0.05],and serum HBsAg levels were(925.1±226.9)IU/ml and(816.2±175.3)IU/ml,significantly lower than[(1028.4±251.5)IU/ml and(921.7±226.8)IU/ml,P<0.05]in TAF-treated patients;serum HBeAg negativity rates was 21.3%and 29.5%,both significantly higher than 3.3%and 6.6%(P<0.05)in TAF group;serum TLR4 levels were(68.6±17.4)pg/mL and(41.4±15.9)pg/mL,both much lower than[(90.1±20.5)pg/mL and(73.5±18.2)pg/mL,respectively,P<0.05],and serum IL-35 levels were(127.9±25.5)pg/mL and(73.5±18.6)pg/mL,both much lower than[(191.4±30.6)pg/mL and(102.7±26.1)pg/mL,respectively,P<0.05]in TAF group.Conclusion TAF and PEG-IFNα-2b combination in treatment of patients with CHB is efficacious,with a satisfactory serumHBeAg negativity,which might be related to reduced expressions of TLR4 and IL-35 and needs further investigation.