[HBeAg阳性慢性乙型肝炎患者阴虚证体质与HLA-DQA1基因多态性及聚乙二醇干扰素α治疗反应的相关性]

[Correlation between Constitution of Yin Deficiency Syndrome and Polymorphism of HLA-DQA1/Treatment Response of Peg-IFNalpha Therapy in HBeAg Positive Chronic Hepatitis B Patients].

作者信息

Guo Jian-chun, Deng Xiao-mei, Wu Jing, Xun Yun-hao, Huang Xiao-xiao, Wang Wei-wei, Shi Wei-zhen

出版信息

Zhongguo Zhong Xi Yi Jie He Za Zhi. 2016 May;36(5):539-43.

Abstract

OBJECTIVE

To observe the correlation between constitution of yin deficiency syndrome (YDS) and polymorphism of HLA-DQA1/treatment response of Peg-lFNalpha therapy in HBeAg positive chronic hepatitis B (CHB) patients, and to explore constitution of Chinese medicine (CM) in response of interferon therapy.

METHODS

Totally 120 HBeAg positive CHB patients who were treated with Peg-IFNalpha were enrolled, and assigned to YDS group (59 cases) and non-YDS group (61 cases) according to classification of CM constitutions. All patients were subcutaneously injected with Peg-IFNalpha-2b (1.0 microg/kg body weight) or Peg-IFNalpha-2a (180 microg), once per week. Effective efficacy was primarily judged when complete response (CR) or partial response (PR) was obtained at month 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-IFNalpha 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) vs. 9.8% (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 (Pc > 0.05 for both).

CONCLUSIONS

Both constitutions of CM and HLA-DQA1 gene polymorphism af- fect HBeAg positive CHB patients' response to Peg-INFalpha. Constitutions of YDS and HLA-DQA1 * 0501 was not favorable to response, their association needed to be further studied.

摘要

目的

观察HBeAg阳性慢性乙型肝炎（CHB）患者阴虚体质与HLA - DQA1基因多态性及聚乙二醇干扰素α（Peg - IFNα）治疗反应的相关性，探讨中医体质在干扰素治疗应答中的作用。

方法

选取120例接受Peg - IFNα治疗的HBeAg阳性CHB患者，根据中医体质分类分为阴虚体质组（59例）和非阴虚体质组（61例）。所有患者皮下注射聚乙二醇干扰素α - 2b（1.0μg/kg体重）或聚乙二醇干扰素α - 2a（180μg），每周1次。主要在治疗6个月时以获得完全缓解（CR）或部分缓解（PR）判断疗效。获得CR或PR的患者完成1年疗程。采用聚合酶链反应序列特异性引物（PCR - SSP）法检测HLA - DQA1基因分型。比较CR或PR患者中医体质分布差异及组间HLA - DQA1等位基因频率。

结果

两种不同中医体质的CHB患者对Peg - IFNα治疗反应不同。阴虚体质组CR + PR比例为61.0%（36/59），明显低于非阴虚体质组[78.7%（48/61），P < 0.05]。CR患者HLA - DQA1 * 0501等位基因频率低于无应答患者[14.8%（8/54）对30.6%（22/72）]，差异有统计学意义（P < 0.05）。CR患者HLA - DQA1 * 0601等位基因频率高于无应答患者[18.5%（10/54）对5.6%（4/72）]，差异有统计学意义（P < 0.05）。阴虚体质组HLA - DQA1 * 0301等位基因频率低于非阴虚体质组[2.5%（3/118）对9.8%（12/122）]，差异有统计学意义（P < 0.05）。阴虚体质组HLA - DQA1 * 0501等位基因频率高于非阴虚体质组[33.9%（40/118）对18.9%（23/122）]，差异有统计学意义（P < 0.05）。但校正后差异无统计学意义（两者P c> 0.05）。