慢性乙型肝炎遗传变异及对聚乙二醇干扰素的反应

StephenW

Genetic Variants and Response to Peg Interferon in Chronic Hepatitis B
Virginia Schad, PharmD
The current Genome Wide Association Study (GWAS) identified genetic variants that are associated with both short- and long-term responses to pegylated interferon (Peg IFN) in patients with chronic hepatitis B (CHB), according to study results published in Clinical Infectious Diseases .1

Peg IFN is used to reduce viral load and hepatic necroinflammation in patients with CHB infection, thus decreasing the risk for hepatocellular carcinoma and the complications of cirrhosis. 2-4 However, in addition to considerable adverse effects, only 20% to 30% of Patients have a sustained response to treatment. 5-8, researchers sought to determine host genetic determinants of response in order to reduce the costs and side effects of treatment by order 1058 patients with CHB treated with Peg IFN for at least 12 weeks with or Without nucleos (t)ide analogues from 21 centers in Europe, Asia, and North America.1

Response at 24 weeks after Peg IFN treatment was defined as combined HBeAg-loss with HBVDNA <2000 IU/mL, or an HBVDNA <2000 IU/mL in patients who are HBeAg-negative. They found that 282 (31%) patients achieved the Single and long-term responses to Peg IFN in patients with CHB who were HBeAg -positive and HBeAg-negative, respectively.

This was the first and largest GWAS study about patients with CHB who were treated with PegIFN to date.1 The investigators concluded that, "Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with PegIFN response in CHB. "In addition, "The current findings could pave the way for gene polymorphism-guided clinical counselling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies."


References

    Brouwer WP, Chan HLY, Lampertico P, et al. Genome wide association study identifies genetic variants associated with early and sustained response to (Peg) Interferon in chronic hepatitis B patients: the GIANT-B study [published on February 2, 2019]. Clin Infect Dis. doi: 10.1093/cid/ciz084

StephenW

慢性乙型肝炎遗传变异及对聚乙二醇干扰素的反应
Virginia Schad，PharmD
根据临床传染病发表的研究结果，目前的全基因组关联研究（GWAS）确定了与慢性乙型肝炎（CHB）患者对聚乙二醇化干扰素（Peg IFN）的短期和长期反应相关的遗传变异。 0.1

Peg IFN用于降低CHB感染患者的病毒载量和肝脏坏死性炎症，从而降低肝细胞癌和肝硬化并发症的风险。 2-4然而，除了相当大的不良反应外，只有20％至30％的患者对治疗有持续的反应。 5-8，研究人员试图确定反应的宿主遗传决定因素，以减少治疗的成本和副​​作用，通过订购1058名用Peg IFN治疗至少12周的CHB患者，其中有或没有来自21的核苷酸（t）ide类似物欧洲，亚洲和北美的中心

Peg IFN治疗后24周的反应定义为HBeAg消失，HBVDNA <2000 IU / mL，或HBVDA <2000 IU / mL，HBeAg阴性患者。他们发现，282例（31％）患者分别在HBeAg阳性和HBeAg阴性的CHB患者中实现了对Peg IFN的单期和长期反应。

这是迄今为止用PegIFN治疗CHB患者的第一次也是最大的GWAS研究。研究人员得出结论：“尽管没有发现全基因组显着的命中，但目前的GWAS确定了与CHB中PegIFN反应相关的遗传变异。 “此外，”目前的研究结果可能为基因多态性指导的临床咨询铺平道路，无论是在（Peg）IFN和自然史的环境中，还是可能用于新的免疫调节疗法。


参考

Brouwer WP，Chan HLY，Lampertico P，et al。全基因组关联研究确定了与慢性乙型肝炎患者（Peg）干扰素的早期和持续反应相关的遗传变异：GIANT-B研究[发表于2019年2月2日]。 Clin Infect Dis。 doi：10.1093 / cid / ciz084