IL28B基因多态性对HBeAg阴性慢性乙型肝炎患者抗病毒疗效及停药后复发的影响  

Impact of IL28B gene polymorphism on antiviral effect and relapse after drug withdrawal of HBeAg-negative chronic hepatitis B patients

作　　者：李莎[1] 莫雨灵 吕建楠 LI Sha;MO Yu-ling;Lü Jian-nan(Department of Medicine,the Fourth People’s Hospital of Nanning,530023,China)

机构地区：[1]南宁市第四人民医院综合内科,530023 [2]南宁市第四人民医院肝病科,530023 [3]北海市人民医院感染科,536000

出　　处：《传染病信息》2021年第4期306-309,334,共5页Infectious Disease Information

基　　金：北海市科学研究与技术开发计划项目(北科合201506003,北科合201777032);广西壮族自治区卫生健康委员会自筹经费科研课题(Z20201108)。

摘　　要：目的探讨IL28B基因多态性对替诺福韦(tenofovir disoproxil fumarate, TDF)序贯或联合普通IFN-α治疗HBeAg阴性慢性乙型肝炎(chronic hepatitis B, CHB)的效果及停药后复发的影响。方法选取2016年1月-2019年12月在南宁市第四人民医院和北海市人民医院门诊或住院的119例初次接受TDF治疗有效并完成序贯或联合普通IFN-α抗病毒治疗的HBeAg阴性CHB患者作为研究对象。根据治疗144周时HBsAg水平对患者进行分组,依据治疗192周时HBsAg水平决定是否停药;采用PCR产物测序方法对患者IL28B rs12979860多态性进行测序分型,探讨IL28B基因多态性与抗病毒疗效及停药后复发的关系。结果对不同IL28B rs12979860基因型患者的基线特征进行比较,差异均无统计学意义(P均> 0.05)。治疗192周时,IL28B rs12979860 CC基因型患者中HBsAg≤1000 IU/ml者占65.7%(65/99),而非CC基因型患者中HBsAg≤1000 IU/ml者仅占35.0%(7/20),2组比较差异有统计学意义(P <0.05);IL28B rs12979860 CC基因型患者HBsAg下降水平为(1.0±0.4)lgIU/ml,而非CC基因型者仅为(0.8±0.3)lgIU/ml(P <0.05);IL28B rs12979860 CC基因型患者肝脏弹性值的平均下降水平为(3.4±1.3) kPa,而非CC基因型者仅为(2.6±1.4) kPa(P <0.05)。停药随访6个月,IL28B rs12979860 CC基因型和非CC基因型患者停药后复发的比例分别为16.9%(11/65)及71.4%(5/7),差异有统计学意义(P <0.05)。对抗病毒治疗期间的IL28B rs12979860 CC基因型和非CC基因型患者主要的药物不良反应发生率比较,差异均无统计学意义(P均> 0.05)。结论 HBeAg阴性CHB患者应用TDF序贯或联合IFN-α治疗可以获得较好的血清学及组织学应答,IL28B rs12979860 CC基因型可能是HBeAg阴性CHB患者抗病毒治疗获得血清学和组织学应答及停药6个月不复发的预测因素。Objective To explore the impact of IL28 B gene polymorphism in the antiviral effect using tenofovir disoproxil fumarate(TDF) sequentially or combined with conventional IFN-α and the relapse after drug withdrawal in HBeAg-negative chronic hepatitis B(CHB) patients. Methods A total of 119 outpatients or inpatients with HBeAg-negative chronic HBV infection who received TDF treatment for the first time and completed sequential or combination of conventional IFN-α antiviral therapy in the Fourth People’s Hospital of Nanning and Beihai People’s Hospital from January 2016 to December 2019 were included as the study subjects. According to the level of HBsAg at 144 weeks of therapy, the subjects were divided into groups. According to the HBsAg level at 192 weeks of therapy, the drug withdrawal was determined. The sequencing and typing of IL28 B rs12979860 polymorphism were performed by PCR, and the association between IL28 B rs12979860 gene polymorphism and antiviral efficacy and relapse after drug withdrawal was analyzed. Results There was no statistical difference in baseline characteristics among carriers of different IL28 B rs12979860 genotypes(P >0.05). At 192 weeks of therapy, the proportion of HBsAg ≤ 1000 IU/ml was 65.7%(65/99) in rs12979860 CC genotype patients, but only 35.0%(7/20) in non-CC genotype patients, with statistical difference between 2 groups(χ^(2)=6.544, P=0.011). The decrease of HBsAg in IL28 B rs12979860 CC genotype patients was(1.0±0.4) lg IU/ml, while that in nonCC genotype patients was(0.8±0.3) lg IU/ml(P <0.05);the decrease of liver stiffness measurement was(3.4±1.3) kPa in IL28 B rs12979860 CC genotype patients, but only(2.6±1.4) kPa in non-CC genotype patients(P <0.05). The relapse rate within 6 months after drug withdrawal was 16.9%(11/65) and 71.4%(5/7) in CC and non-CC genotype patients, with statistical difference(P <0.05). There was no statistical difference in the incidence of main drug adverse reactions during the antiviral therapy in patients carrying IL28 B rs12979860 C

关 键 词：IL28B基因 多态性 慢性乙型肝炎 疗效 

分 类 号：R512.62[医药卫生—内科学]