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肝组织中 hepcidin 的表达水平与聚乙二醇干扰素-α治疗乙型肝炎的疗效相关。

Hepcidin expression levels involve efficacy of pegylated interferon-α treatment in hepatitis B-infected liver.

机构信息

Department of Clinical Laboratory, the Second Hospital of Anhui Medical University, Hefei 230601, China.

School of Pharmacy, Institute for Liver Diseases of Anhui Medical University, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province 230032, China.

出版信息

Int Immunopharmacol. 2022 Jun;107:108641. doi: 10.1016/j.intimp.2022.108641. Epub 2022 Feb 22.

Abstract

BACKGROUND

Hepcidin is the master iron regulator hormone produced by the liver. The association of serum hepcidin with pegylated interferon therapy in patients with chronic hepatitis C infection has been studied. However, the role of serum hepcidin level in predicting the effect of pegylated interferon treatment in patients with chronic hepatitis B (CHB) infection is yet to be elucidated. Our study aims to investigate the correlation between hepcidin expression levels and the curative effect of interferon-alpha therapy in patients with CHB.

METHODS

A total of 47 patients with CHB who accepted pegylated interferon-α (PEG-IFN- α) treatment were recruited. The serum level of hepcidin was estimated by ELISA. The alternation in the gene expression level of hepcidin was detected by RT-PCR, and immunofluorescence cell staining was performed to detect hepcidin peptide. The induction of antiviral proteins was analyzed by Western blotting. The predictive value of early on-treatment variation in serum hepcidin during treatment progress was assessed by receiver operating characteristic analysis.

RESULTS

High levels of early on-treatment serum hepcidin were observed in patients who achieved a decline in HBsAg > 1 log10 IU/mL or HBV DNA > 1 log10 IU/mL. In vitro, an elevation of the hepcidin expression in HepG2.2.15 cells induced by PEG-IFN-α treatment was noted. Furthermore, combined treatment with hepcidin and PEG-IFN-α increased the levels of antiviral proteins. The predictive cut-off value of hepcidin for HBsAg decline > 1 log10 IU/mL was 239 pg/mL, and the sensitivity and specificity were 72.73% and 70.97%, respectively. The predictive cut-off value of hepcidin for the decline in HBV DNA > 1 log10 IU/mL was 190.4 pg/mL, and the sensitivity and specificity were 72.73% and 61.11%, respectively. Early-on treatment changes in the hepcidin level signified the predictive value of the PEG-IFN-α curative effect.

CONCLUSIONS

A higher early-on treatment hepcidin level indicates a higher possibility of HBsAg and HBV DNA decline in patients with CHB during PEG-IFN-α treatment. A high early-on treatment serum hepcidin level is significant in predicting the PEG-IFN-α therapeutic effect in patients with CHB.

摘要

背景

铁调素是肝脏产生的主要铁调节激素。已经研究了血清铁调素与慢性丙型肝炎感染患者聚乙二醇干扰素治疗的相关性。然而,血清铁调素水平在预测慢性乙型肝炎(CHB)感染患者聚乙二醇干扰素治疗效果中的作用尚不清楚。我们的研究旨在探讨铁调素表达水平与 CHB 患者干扰素-α治疗疗效的相关性。

方法

共纳入 47 例接受聚乙二醇干扰素-α(PEG-IFN-α)治疗的 CHB 患者。采用 ELISA 法检测血清铁调素水平。采用 RT-PCR 检测铁调素基因表达水平的变化,免疫荧光细胞染色检测铁调素肽。采用 Western 印迹法分析抗病毒蛋白的诱导。通过受试者工作特征分析评估治疗过程中早期治疗变化对血清铁调素的预测价值。

结果

在 HBsAg 下降>1 log10 IU/mL 或 HBV DNA 下降>1 log10 IU/mL 的患者中观察到治疗早期血清铁调素水平升高。体外实验中,PEG-IFN-α 处理可诱导 HepG2.2.15 细胞中铁调素表达升高。此外,铁调素和 PEG-IFN-α 联合治疗可增加抗病毒蛋白水平。铁调素预测 HBsAg 下降>1 log10 IU/mL 的截断值为 239 pg/mL,敏感性和特异性分别为 72.73%和 70.97%。铁调素预测 HBV DNA 下降>1 log10 IU/mL 的截断值为 190.4 pg/mL,敏感性和特异性分别为 72.73%和 61.11%。治疗早期铁调素水平的变化表明了 PEG-IFN-α 疗效的预测价值。

结论

治疗早期铁调素水平较高提示 CHB 患者接受 PEG-IFN-α 治疗时 HBsAg 和 HBV DNA 下降的可能性更高。治疗早期血清铁调素水平较高在预测 CHB 患者 PEG-IFN-α 治疗效果方面具有重要意义。

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