转化生长因子-β高产基因型与HIV阳性急性丙型肝炎患者对丙型肝炎病毒特异性治疗的反应相关。

The transforming growth factor-beta high-producer genotype is associated with response to hepatitis C virus-specific therapy in HIV-positive patients with acute hepatitis C.

作者信息

Nattermann Jacob, Vogel Martin, Nischalke Hans Dieter, Danta Mark, Ahlenstiel Golo, Michalk Monika, Sauerbruch Tilman, Rockstroh Jürgen K, Spengler Ulrich

机构信息

Department of Internal Medicine I, University of Bonn, Bonn, Germany.

出版信息

AIDS. 2008 Jul 11;22(11):1287-92. doi: 10.1097/QAD.0b013e3282f85daa.

DOI:10.1097/QAD.0b013e3282f85daa

PMID:18580607

Abstract

BACKGROUND

Coinfection with the hepatitis C virus (HCV) in HIV-positive patients is an emerging health problem. The factors affecting response to HCV-specific therapy are poorly understood but may involve host genetic factors. HCV NS5A-induced inhibition of transforming growth factor-beta signaling has been suggested as a potential mechanism involved in HCV pathogenesis. Transforming growth factor-beta, a multifunctional cytokine, displays gene polymorphisms (transforming growth factor-beta codon 10T/C and codon 25G/C) associated with differential cytokine secretion. Here, we studied whether transforming growth factor-beta gene polymorphisms affect treatment response in HCV/HIV coinfection.

METHODS

Transforming growth factor-beta genotypes were determined in 60 HIV-positive patients with acute hepatitis C treated with pegylated interferon-alpha. Patients were classified into those with a high-producer genotype and others with non-high-producer genotypes. Rates of sustained virological responses were compared between high-producer and non-high-producer patients. As a control, 100 healthy, 201 HIV(+)/HCV(-), and 148 HCV(+)/HIV(-) subjects were studied.

RESULTS

Transforming growth factor-beta genotype distribution did not differ significantly between the groups. In HIV/HCV coinfection carriers of the transforming growth factor-beta high-producer genotype had significantly higher sustained virological response rates than patients with a transforming growth factor-beta non-high-producer genotype (75 vs. 41.7%; P = 0.039). In a forward-conditional stepwise regression model, transforming growth factor-beta high-producer genotype was confirmed as an independent positive predictor for sustained virological response in interferon-alpha therapy (odds ratio, 4.4; 95% confidence interval, 1.5-13.4; P = 0.009).

CONCLUSION

Response rates to interferon-alpha therapy are enhanced in acute HCV-infected HIV-positive patients carrying the transforming growth factor-beta 'high-producer' genotype. This finding may indicate that a transforming growth factor-beta 'high-producer' state can partially compensate HCV NS5A-induced inhibition of transforming growth factor-beta signaling.

摘要

背景

HIV阳性患者合并丙型肝炎病毒（HCV）感染是一个新出现的健康问题。影响HCV特异性治疗反应的因素尚不清楚，但可能涉及宿主遗传因素。有人提出，HCV NS5A诱导的对转化生长因子-β信号传导的抑制是参与HCV发病机制的一种潜在机制。转化生长因子-β是一种多功能细胞因子，具有与细胞因子分泌差异相关的基因多态性（转化生长因子-β密码子10T/C和密码子25G/C）。在此，我们研究了转化生长因子-β基因多态性是否影响HCV/HIV合并感染的治疗反应。

方法

对60例接受聚乙二醇化干扰素-α治疗的急性丙型肝炎HIV阳性患者进行转化生长因子-β基因型测定。患者被分为高产基因型患者和非高产基因型患者。比较高产和非高产患者的持续病毒学应答率。作为对照，研究了100名健康人、201名HIV(+)/HCV(-)者和148名HCV(+)/HIV(-)者。

结果

各组间转化生长因子-β基因型分布无显著差异。在HIV/HCV合并感染中，转化生长因子-β高产基因型携带者的持续病毒学应答率显著高于转化生长因子-β非高产基因型患者（75%对41.7%；P = 0.039）。在向前条件逐步回归模型中，转化生长因子-β高产基因型被确认为干扰素-α治疗中持续病毒学应答的独立阳性预测因子（优势比，4.4；95%置信区间，1.5 - 13.4；P = 0.009）。