恩替卡韦联合聚乙二醇干扰素α-2b治疗低水平血清HBsAg阳性的慢性乙型肝炎患者疗效研究

Serologic response toentecavir and pegylated interferon α-2b combination in treatment of patients with low serum level HBsAg-positive chronic hepatitis B

目的探讨应用恩替卡韦(ETV)联合聚乙二醇干扰素α-2b(PEG-IFNα-2b)治疗血清低水平HBsAg阳性的慢性乙型肝炎(CHB)患者的临床疗效。方法2018年1月~2020年1月我院收治的CHB患者96例,采用随机数字表法分成对照组48例和观察组48例,分别给予ETV或ETV联合PEG-IFNα-2b治疗观察48 w。采用荧光定量PCR法检测HBV DNA定量,采用电化学发光法检测血清HBsAg和HBeAg水平,使用流式细胞仪检测外周血CD3^(+)、CD4^(+)和CD8^(+)细胞百分比,并计算CD4^(+)/CD8^(+)细胞比值。结果在治疗48 w末,观察组血清HBsAg和HBeAg水平分别为(809.8±101.5)IU/mL和(193.4±24.5)IU/mL,均显著低于对照组【分别为(1201.7±204.9)IU/mL和(244.2±5.7)IU/mL,P<0.05】;观察组血清HBeAg转阴率为29.2%,显著高于对照组的4.2%(P<0.05),血清HBeAg转换率为12.5%,血清HBsAg转阴率为8.3%;观察组血清ALT和AST水平分别为(52.5±4.6)U/L和(45.1±5.2)U/L,均显著低于对照组【分别为(63.4±5.2)U/L和(68.2±5.4)U/L,P<0.05】;观察组外周血CD3^(+)、CD4^(+)细胞百分比和CD4^(+)/CD8^(+)细胞比值分别为(68.5±4.2)%、(38.1±3.6)%和(1.8±0.5),均显著高于对照组【分别为(57.4±3.8)%、(32.6±3.1)%和(1.1±0.4),P<0.05】,而CD8^(+)细胞百分比为(21.3±1.8)%,显著低于对照组【(28.7±2.0)%,P<0.05】。结论应用ETV联合PEG-IFNα-2b治疗血清低水平HBsAg阳性的CHB患者具有较好的抗病毒疗效,在部分患者获得了血清学应答,可能与应用α-干扰素提高了机体免疫功能有关。

Objective The aim of this study was to explore the antiviral efficacy of entecavir(ETV)and pegylated interferonα-2b(PEG-IFNα-2b)combination in treatment of patients with low serum level HBsAg-positive chronic hepatitis B(CHB).Methods A total of 96 patients with low serum level HBsAg-positive CHB were enrolled in our hospital between January 2018 and January 2020,and were randomly divided into control and observation group,with 48 cases in each group.The patients in the control group were treated with orally ETV and those in the observation were treated with ETV and PEG-IFNα-2b combination for 48 weeks.Serum HBV DNA loads were detected by fluorescence quantitative polymerase chain reaction,and serum HBsAg and HBeAg levels were detected by electrochemiluminescence.The percentages of CD3^(+),CD4^(+)and CD8^(+)cells were detected by flow cytometry,and ratio of CD4^(+)/CD8^(+)cells was calculated.Results At the end of 48 week observation,serum HBsAg and HBeAg levels in the observation group were(809.8±101.5)IU/mL and(193.4±24.5)IU/mL,both significantly lower than[(1201.7±204.9)IU/mL and(244.2±5.7)IU/mL,respectively,P<0.05]in the control;serum HBeAg negative rate was 29.2%,significantly higher than 4.2%(P<0.05)in the control,and the HBeAg seroconversion rate was 12.5%and serum HBsAg loss was 8.3%;serum ALT and AST levels were(52.5±4.6)U/L and(45.1±5.2)U/L,both significantly lower than[(63.4±5.2)U/L and(68.2±5.4)U/L,respectively,P<0.05]in the control;the percentages of peripheral blood CD3^(+)and CD4^(+)cells and the ratio of CD4^(+)/CD8^(+)cells were(68.5±4.2)%,(38.1±3.6)%and(1.8±0.5),all significantly higher than[(57.4±3.8)%,(32.6±3.1)%and(1.1±0.4),respectively,P<0.05],while the percentage of CD8^(+)cells was(21.3±1.8)%,significantly lower than[(28.7±2.0)%,P<0.05]in the control group.Conclusion The regimen with ETV and PEG-IFNα-2b combination in treating CHB patients with low serum HBsAg positive could gain a good antiviral efficacy,with serologic response in some cases,which might be related to the improved immune functions.