基因突变与丙肝治疗反应相关

2006-12-19 00:00 来源:丁香园 作者:lwjssry 译
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纽约(路透社健康栏目)12月13日消息:血色病基因HFE突变使丙肝病毒感染患者肝内铁蓄积增加,但却能增强对干扰素和利巴韦林治疗的反应。

文章的第一作者Dr. Herbert L. Bonkovsky向路透社健康栏目解释道:“我们的研究结果强调了铁作为慢性HCV并存因素的重要性。我们及其他研究者最近得出的这一结论适用于多种肝脏疾病,包括乙型慢性病毒性肝炎、丙型慢性病毒性肝炎、酒精性肝病和非酒精性脂肪肝。”

美国康涅狄格州的Farmington市的康涅狄格州卫生中心附属大学的Dr. Bonkovsky及其同事称,HFE基因突变可增加铁蓄积并影响肝病病情。更进一步,研究者研究了1051名HCV病人并发现35%携带有至少一种HFE基因突变。

然而与不携带HFE基因突变的病人相比,携带者治疗反应终点(携带者40%,非携带者29%)和病毒反应终点(携带者20%,非携带者14%)均显著增高。

Dr. Bonkovsky还说道:“这一惊人发现提示,尽管HFE基因突变,特别是H63D等位基因的遗传性变异,将导致铁在肝脏和肝内血液中的富积,然而另一方面HFE基因突变却能增强目前慢丙肝最佳疗法的治疗反应。”

他总结道:“因此,这一遗传突变是一把双刃剑。”

在该文章的评论中,西雅图华盛顿大学的Drs. Kris V. Kowdley和Jacob Alexander认为这项重要的研究独创性地着眼于铁和HFE基因突变在慢丙肝治疗反应中的作用。

Gene Mutations Linked With Response to HCV Therapy

By Will Boggs, MD

NEW YORK (Reuters Health) Dec 13 - Patients with hepatitis C virus infection (HCV) who carry HFE mutations have increased iron stores within the liver, but they also seem to have increased rates of response to interferon and ribavirin therapy.

"Our results," lead investigator Dr. Herbert L. Bonkovsky told Reuters Health, "emphasize the importance of iron as a comorbid factor in chronic HCV. We and others have pointed this out recently for several liver diseases, including chronic viral hepatitis B and C, alcoholic liver disease, and non-alcoholic fatty liver disease."

Mutations in the HFE gene can increase iron stores and influence liver disease, Dr. Bonkovsky of the University of Connecticut Health Center, Farmington and colleagues note. To investigate further, the researchers studied 1051 HCV patients and found that 35% carried at least one HFE gene mutation.

Nevertheless, compared to those without these mutations, carriers had a significantly higher end of treatment response (40% versus 29%) and virological response (20% versus 14%).

"The striking finding," continued Dr. Bonkovsky "is that although HFE mutations -- especially the H63D genetic variation --led to more iron in the livers and blood of the subjects, they also were associated with improved responses to the current best therapy for chronic hepatitis C."

"Thus," he concluded, "the presence of these genetic variations is a two-edged sword."

In an accompanying editorial, Drs. Kris V. Kowdley and Jacob Alexander of the University of Washington, Seattle conclude that this "important study" has provided "unique insights into the role of iron and HFE mutations in response to treatment in chronic hepatitis virus C."

http://www.medscape.com/viewarticle/549335


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