HLA-DP多态性与响应聚乙二醇干扰素在白种人患者的慢性乙肝

StephenW

Source: Aliment Pharmacol Ther  |  Posted 1 day ago
Polymorphisms of HLA-DP are associated with response to peginterferon in Caucasian patients with chronic hepatitis B; Brouwer W, Sonneveld M, Tabak F, Simon K, Cakaloglu Y, Akarca U, Zeuzem S, Ferenci P, Heathcote J, de Knegt R, Boonstra A, Hansen B, Janssen H; Alimentary Pharmacology & Therapeutics (Aug 2014)

   
BACKGROUND Polymorphisms of the HLA-DP gene are associated with the natural clearance of the hepatitis B virus in Asian patients.

AIM To investigate the association of HLA-DP polymorphisms with response to peginterferon (PEG-IFN) in Caucasian chronic hepatitis B (CHB) patients.

METHODS We studied 262 Caucasian chronic hepatitis B patients infected with HBV genotype A or D, treated with PEG-IFN for 1 year in two randomised controlled trials (HBV 99-01 and PARC study). Response was defined as an HBV DNA<2000 IU/mL at 6 months post-treatment. Variations at HLA-DPA1 and HLA-DPB1 were genotyped.

RESULTS Of the 262 patients, 58% was HBeAg-positive and HBV genotype A and D was observed in 32% and 68%, respectively. At 6 months post-treatment, 57 (22%) patients had achieved an HBV DNA<2000 IU/mL. HLA-DPB1 was independently associated with virological response [adjusted odds ratio (OR) 1.8, 95% confidence interval (CI):1.1-3.0, P = 0.025], and with an undetectable HBV DNA (adjusted OR 2.4 95% CI: 1.2-4.7, P = 0.015) when adjusted for HBeAg status and other known response modifiers. In HBeAg-positive patients, combined HBeAg seroconversion with HBV DNA<2000 IU/mL was increasingly observed with each addition of an HLA-DPB1 G-allele (adjusted OR 2.7, 95% CI: 1.2-5.9, P = 0.012). Furthermore, HLA-DPA1 and HLA-DPB1 haplotype block GG showed comparable results for virological and combined response.

CONCLUSION In this large cohort of Caucasian chronic hepatitis B patients infected with HBV genotypes A or D, polymorphisms of HLA-DP are independently associated with both virological and serological response to PEG-IFN therapy at 6 months post-treatment.

StephenW

资料来源：滋养品药理有|发布时间1天前
HLA-DP多态性与响应聚乙二醇干扰素在白种人患者的慢性乙肝相关性;布劳威尔W，Sonneveld男，塔巴克楼西门K，Cakaloglu Y，Akarca U，Zeuzem S，Ferenci磷，希思科特Ĵ，德Knegt R，Boonstra A，汉森B，扬森H;消化系统药理学与治疗学（2014年8月）

   
与HLA-DP基因的背景多态性与乙型肝炎病毒的亚洲患者的自然间隙有关。

目的探讨HLA-DP多态性的关联与响应聚乙二醇干扰素（PEG-IFN）的白人慢性乙型肝炎（CHB）患者。

方法我们研究了感染HBV基因型A或D，用PEG-IFN的两项随机对照试验治疗1年262高加索慢性乙肝患者（乙肝99-01和PARC的研究）。反应定义为HBV DNA<2000 IU/ mL的6个月后处理。变型在HLA-DPA1和HLA-DPB1进行基因分型。

结果在262例患者中，58％的HBeAg阳性和HBV基因型A和D，观察分别为32％和68％。 6个月治疗后，有57（22％）的患者已经达到了HBV DNA<2000 IU/ mL的。 HLA-DPB1独立与病毒学应答[校正比值比（OR）1.8，95％可信区间（CI）：1.1-3.0，P = 0.025]关联，并与检测不到HBV DNA（校正OR为2.4％CI：1.2 -4.7，P = 0.015）时，调整为HBeAg状态和其他已知的反应调节剂。在HBeAg阳性患者，合并HBeAg血清转换与HBV DNA<2000 IU/ mL的越来越多，每次加一个HLA-DPB1 G-等位基因的发现（校正OR2.7，95％CI：1.2-5.9，P = 0.012）。另外，HLA-DPA1和HLA-DPB1单倍型区段的GG表明比较的结果为病毒学和结合反应。

结论在感染HBV基因型A或D高加索慢性乙型肝炎患者的这一大组中，HLA-DP的多态性与独立的6个月治疗后均病毒学和血清学反应的PEG-IFN治疗有关

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