HBeAg阳性慢性乙型肝炎患者阴虚体质、HLA-DQA1基因多态性及Peg-IFNα治疗应答的相关性

Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNα Therapy in HBe Ag Positive Chronic Hepatitis B Patients

目的观察中医阴虚体质与HBeAg阳性慢性乙型肝炎(chronic hepatitis B,CHB)患者聚乙二醇干扰素α(Peg-IFNα)治疗应答及人类白细胞抗原(HLA)DQA1基因多态性的关系,探讨中医体质因素在干扰素治疗应答中的作用。方法收集行Peg-IFNα治疗的120例HBeAg阳性CHB患者资料,通过体质分类判定中医体质类型后分为阴虚质组(59例)和非阴虚质组(61例)。两组均应用Peg-IFNα-2b(1.0μg/kg体重)或Peg-IFNα-2a(180μg)皮下注射,每周1次;6个月后获得完全应答(CR)或部分应答(PR)初步判断为治疗有效,有治疗应答者完成1年疗程。采用聚合酶链反应序列特异性引物法(PCR-SSP)检测HLADQA1基因型。比较不同应答情况患者体质类型分布及组间基因频率的差异。结果不同体质类型CHB患者Peg-IFNα治疗应答存在差异,阴虚质组有效率[61.0%(36/59)]明显低于非阴虚质组[78.7%(48/61)],差异有统计学意义(P<0.05)。CR患者HLA-DQA1*0501等位基因频率为14.8%(8/54),明显低于无应答(NR)患者的30.6%(22/72);HLA-DQA1*0601等位基因频率为18.5%(10/54)则高于NR患者的5.6%(4/72),差异均有统计学意义(P<0.05)。阴虚质患者HLA-DQA1*0301等位基因频率[2.5%(3/118)]低于非阴虚质患者[9.8%(12/122)],而HLA-DQA1*0501等位基因频率[33.9%(40/118)]高于非阴虚质组患者[18.9%(23/122)],差异均有统计学意义(P<0.05),但校正后差异无统计学意义(P_c>0.05)。结论中医体质和HLA-DQA1基因多态性影响HBeAg阳性CHB患者对Peg-IFNα的应答,阴虚体质和HLA-DQA1*0501基因型不利于应答,但其关系尚有待明确。

Objective To observe the correlation between constitution of yin deficiency syndrome（YDS）and polymorphism of HLA-DQA1/treatment response of Peg-IFNα therapy in HBe Ag positive chronic hepatitis B（CHB） patients, and to explore constitution of Chinese medicine（CM） in response of interferon therapy. Methods Totally 120 HBe Ag positive CHB patients who were treated with Peg-IFNα were enrolled, and assigned to YDS group（59 cases） and non-YDS group（61 cases） according to classification of CM constitutions. Al patients were subcutaneously injected with Peg-IFNα-2b（1. 0 μg/kg body weight） or Peg-IFNα-2a（180 μg）, once per week. Effective efficacy was primarily judged when complete response（CR） or partial response（PR） was obtained atmonth 6. Those with CR or PR completed 1 year therapeutic course. HLA-DQA1 gene types were detected by polymerase chain reaction sequence specific primers（PCR-SSP）. The distribution difference of CM constitutions in patients with CR or PR and their inter-group HLA-DQA1 allele frequency were compared. Results Different treatment responses of Peg-IFNα were observed in CHB patients of two different CM constitutions. The ratio of CR ＋PR was 61. 0%（36/59） in YDS group, obviously lower than that in NYDS group [78. 7%（48/61）, P〈0. 05]. Patients with CR had a lower allele frequency of HLA-DQA1＊ 0501 than those with no-response [14. 8%（8/54） vs.30. 6%（22/72）] with statistical difference（P〈0. 05）. Patients with CR had a higher allele frequency of HLA-DQA1＊ 0601 than those with no-response [18.5%（10/54） vs. 5.6%（4/72）] with statistical difference（P〈0.05）.The allele frequency of HLA-DQA1 ＊ 0301 was lower in YDS group than in non-YDS group [2. 5%（3/118） vs9. 8%（12/122）] with statistical difference（P〈0. 05）. The allele frequency of HLA-DQA1 ＊ 0501 was higher in YDS group than in non-YDS group [33. 9%（40/118） vs 18. 9%（23/122）]with statistical difference（P〈0. 05）. Yet statistical significance was lost after adjustment（P_c 0. 05 for both）. Conclusions Both constitutions of CM and HLA-DQA1 gene polymorphism affect HBe Ag positive CHB patients ＇response to Peg-INFα. Constitutions of YDS and HLA-DQA1＊ 0501 was not favorable to response, their association needed to be further studied.