新技术理论跟踪~~宿主基因对于干扰素对乙肝的治疗有预期效应

liver411

全世界3.5亿乙肝患者. 乙肝造成慢性肝炎, 肝硬化, 肝癌, 每年全球有1.2百万人死于与乙肝相关的疾病. 目前治疗乙肝的药物有: interferon alfa, Epivir-HBV (lamivudine), Hepsera (adefovir) or Viread (tenofovir). 其中干扰素的效益只有25%-40%, 问题在于缺乏有效的效应, 原因未知.

最近越来越多科学家对于病毒的亚型产生兴趣, 认为不同的基因型病毒对干扰素有不同的效应. 前日, 科学家发现宿主对于干扰素产生效应的基因组合和干扰素治疗乙肝的效益有关. 这组基因缩写叫"SNP", 即: single nucleotide polymorphisms. 下面这个文摘讲述了几组对比病人在SNP和干扰素效益的结果. (不另) 研究结果表明, SNP和干扰素有直接关系.

目前, SNP的商业性用途还没有展开. 但是人们已经开始认识到, 特别是在疾病图同期识别不同的SNP可以在预期药效, 治疗方案等等方面产生剧烈变化.


原文:




[B]Host Genes May Be Predictive of Response to Interferon Therapy for HBV[/B]
By Brian Boyle, MD

Hepatitis B virus (HBV) infection infects over 350 million people worldwide and is a significant cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Chronic HBV infection has been estimated to result in more than 1.2 million deaths per year because of acute or chronic disease.

Treatment is generally recommended for patients with chronic HBV and with detectable HBV e antigen (HBeAg) or DNA and elevated alanine aminotransferase (ALT) serum levels. Options for treatment now include interferon alfa, Epivir-HBV (lamivudine), Hepsera (adefovir) or Viread (tenofovir). Treatment with interferon alfa results in a sustained remission of HBV in only 25% to 40% of chronic HBV patients and the reasons for this relatively poor and variable response have not been well defined.

In a study published in Hepatology, researchers evaluated the host single nucleotide polymorphisms (SNPs) that might be predictive of an interferon response in HBV patients. They selected genes in the interferon pathway involved in antiviral and signaling activities and sequenced 22 SNPs for 82 patients.

The researchers found that 2 SNPs in the antiviral pathway influenced interferon response. One SNP, in the regulatory region of the eIF-2 gene, had A/G alleles and these appeared to affect response rates to interferon. The rate of A/G heterozygotes was 22% in nonresponders to interferon therapy and 2% in sustained responders (Odds ration [OR] 12.82; 95% Confidence Intervals [CI]: 1.52-107.85, P = .009).

Using a multivariate analysis that adjusted for age, sex, and HBV DNA level, the OR reached 14.94 (95% CI: 1.45-153.71, P = .023) and this SNP had greater significance than HBV DNA levels as a predictor of interferon response. Another SNP, in the MxA gene promoter region, revealed G/T alleles of borderline significance. The G/T heterozygote rate was 19% in nonresponders to interferon and 43% in sustained responders (P = .061).

The authors conclude, "the importance of identifying potential SNP markers in predicting clinical response should not be downplayed. Our results supported the potential clinical usefulness of host SNPs over conventional predictors of treatment response (i.e., HBV DNA levels, ALT, and others).

"In light of recent improvements in SNP detection methods and of the potential for efficient mass screening, the greater specificity in using SNPs combined with conventional predictors of treatment response may allow physicians to individualize the medical regimen for each patient.

"The multiple discoveries of associations between SNPs and a wide variety of disease states, in combination with advances in novel SNP detection technology that allows rapid screening of a large amount of patient samples, yield a powerful knowledge base and tools to predict and change the course of patient care and treatment in the future."

12/06/02

Reference
J King and others. Genetic polymorphisms in interferon pathway and response to interferon treatment in hepatitis B patients: A pilot study. Hepatology 2002; 36:1416-1424.


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