聚乙二醇干扰素 α-2a 注射后慢性丙型肝炎患者体温升高与病毒学应答相关，并受 IL28B 基因型调节。

Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.

机构信息

Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

出版信息

J Hepatol. 2013 Nov;59(5):957-63. doi: 10.1016/j.jhep.2013.07.004. Epub 2013 Jul 10.

DOI:10.1016/j.jhep.2013.07.004

PMID:23850879

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3856983/

Abstract

BACKGROUND & AIMS: Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity.

METHODS

60 treatment-naïve patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24h and the maximal increase from baseline during that time (ΔTmax) was determined. Serum HCV-RNA, interferon-gamma-inducible protein-10 (IP-10) and expression of interferon-stimulated genes (ISGs - CD274, ISG15, RSAD2, IRF7, CXCL10) in peripheral blood mononuclear cells (PBMCs) were measured at very early time points, and response kinetics calculated. The IL28B single nucleotide polymorphism, rs12979860, was genotyped.

RESULTS

Temperatures rose by 1.2±0.8°C, peaking after 12.5h. ΔTmax was strongly associated with 1st phase virological decline (r=0.59, p<0.0001) and was independent of gender, cirrhosis, viral genotype or baseline HCV-RNA. The association with 1st phase decline was seen in patients with rs12979860CC genotype (r = 0.65, p <0.0001) but not in CT/TT (r = 0.13, p = 0.53) and patients with CC genotype had a higher DTmax (1.4 ± 0.8 C vs. 0.8 ± 0.6 +C, p = 0.001). DTmax was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12979860CC [corrected].ΔTmax weakly predicted early virological response (AUC=0.68, CI 0.49-0.88).

CONCLUSIONS

Temperature rise following peginterferon injection is closely associated with virological response and is modulated by IL28B polymorphism, reflecting host interferon-responsiveness.

摘要

背景与目的

慢性丙型肝炎的干扰素治疗与发热等非特异性症状相关。我们旨在确定体温变化与干扰素抗病毒活性的关系。

方法

60 例初治慢性丙型肝炎患者（67%基因型 1/4/6，33%基因型 2/3）入组一项临床试验开始接受聚乙二醇干扰素 alfa-2a 和利巴韦林治疗。在最初 24 小时内，在基线和每日 3 次测量体温，并确定这段时间内的最大体温升高（ΔTmax）。在非常早期时间点测量外周血单个核细胞（PBMC）中的血清 HCV-RNA、干扰素-γ诱导蛋白-10（IP-10）和干扰素刺激基因（ISGs - CD274、ISG15、RSAD2、IRF7、CXCL10）的表达，并计算反应动力学。对 IL28B 单核苷酸多态性 rs12979860 进行基因分型。

结果

体温升高 1.2±0.8°C，在 12.5 小时时达到峰值。ΔTmax 与第 1 相病毒学下降呈强烈相关（r=0.59，p<0.0001），与性别、肝硬化、病毒基因型或基线 HCV-RNA 无关。rs12979860CC 基因型患者中观察到与第 1 相下降的相关性（r = 0.65，p <0.0001），而 CT/TT 基因型患者中无相关性（r = 0.13，p = 0.53），且 CC 基因型患者的 DTmax 更高（1.4 ± 0.8°C 比 0.8 ± 0.6°C，p = 0.001）。DTmax 与血清 IP-10 和 PBMC ISG 表达的 6 小时和 24 小时诱导相关，但仅在 rs12979860CC 患者中相关[校正]。ΔTmax 对早期病毒学应答有弱预测作用（AUC=0.68，CI 0.49-0.88）。