干扰素α-1b联合替比夫定序贯治疗慢性乙型肝炎的疗效及其对患者sPD-1和sICOS水平的影响

Curative effect and mechanism analysis of ordinary interferon combined with telbivudine in sequentially treating patients with chronic hepatitis B

目的观察干扰素α-1b(IFNα-1b)联合替比夫定序贯治疗乙型肝炎的疗效,并探讨其对患者血清中可溶性程序性死亡蛋白1(s PD-1)和可溶性可诱导共刺激分子(s ICOS)水平的影响。方法选取我院2012年1月至2013年5月符合条件的患者80例,按随机数表法随机分为观察组和对照组,每组40例。两组患者均给予IFNα-1b治疗,50 g/次,隔日1次,肌内注射。对照组继续给予IFNα-1b巩固治疗,用量同前,疗程12个月。观察组口服替比夫定序贯治疗,600 mg/次,1次/d,疗程12个月。比较两组患者治疗后的应答有效率以及治疗前后的血清s PD-1和s ICOS水平,检测两组患者的门冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)及γ-谷氨酸酰基转移酶(GGT),并参照慢性肝病量表(CLDQ)评价生活质量。结果观察组患者的完全应答率和部分应答率分别为50.0%(20/40)和37.5%(15/40),均高于对照组的40.0%(16/40)和25.0%(10/40),差异均有统计学意义(P<0.05);观察组患者治疗后的CLDQ量表各项评分均明显高于对照组,差异均有显著统计学意义(P<0.01);观察组治疗后AST[(26.56±2.85)U/L]、ALT[(30.28±3.23)U/L]和GGT[(34.26±3.58)U/L]水平均显著低于对照组(P<0.01);观察组治疗后血清中s PD-1和s ICOS水平分别为(404.27±41.26)pg/m L和(35.78±3.91)pg/m L,均明显低于对照组的(517.91±52.55)pg/m L和(44.36±4.56)pg/m L,差异均有显著统计学意义(P<0.01)。结论 IFNα-1b联合替比夫定序贯治疗乙型肝炎可明显改善患者生活质量,提高应答总有效率,其抑制患者血清中s PD-1和s ICOS水平表达可能在治疗中发挥重要作用。

Objective To observe the clinical efficacy of ordinary interferon alpha-1b(IFNα-1b) combined with telbivudine in sequentially treating patients with chronic hepatitis B and its effect on serum soluble apoptosis protein 1(s PD-1) and soluble inducible costimulatory molecule(s ICOS). Methods According to the random number table method, a total of 80 eligible cases, who admitted to our hospital from January 2012 to May 2013, were randomly divided into control group and treatment group, with 40 cases in each group. Patients in both groups received IFNα-1b by intramuscular injection once every two days(50 g each time). The control group was given consolidation therapy of IFNα-1b for 12 months; The treatment group was given telbivudine in sequential treatment for 12 months(600 mg each time). Response rates after treatment were compared and serum s PD-1 and s ICOS were detected in both groups before and after treatment. Indexes of liver function aspartate aminotransferase(AST), alanine aminotransferase(ALT), andγ-glutamyl transpeptidase(GGT) were measured in two groups. Life treatment evaluations in both groups were compared according to Chronic Liver Disease Questionnaire(CLDQ). Results Complete response rate [50.0%(20/40)]and part response rate [37.5%(15/40)] in treatment group were higher than those in control one [40.0%(16/40),25.0%(10/40), respectively] with statistical difference(χ2=4.418, P<0.05). After treatment, scores of CLDQ in treatment group were evidently higher than control one(P<0.01); Levels of AST [(26.56±2.85) U/L], ALT [(30.28±3.23) U/L], and GGT [(34.26 ± 3.58) U/L] in the treatment group were significantly lower than those in control group after treatment(P<0.01). After treatment, levels of serum s PD-1 [(404.27 ± 41.26) pg/m L] and s ICOS [(35.78 ± 3.91) pg/m L] in the treatment group were obviously lower than control group [(517.91±52.55) pg/m L,(44.36±4.56) pg/m L, respectively]with statistical difference(P<0.01). Conclusion Ordinary interferon combined with telbivudine in sequentially treating patients with chronic hepatitis B could notably improve patients’ life quality and increase the response efficient rates.Its role may be related to suppressing the levels of s PD-1 and s ICOS in serum.