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一项关于循环成纤维细胞生长因子21作为4型慢性丙型肝炎肝损伤新型无创生物标志物的研究:埃及患者及其对直接抗病毒药物的反应。

A study of the circulating fibroblast growth factor 21 as a novel noninvasive biomarker of hepatic injury in genotype-4 chronic hepatitis C: Egyptian patients and their response to direct-acting antiviral agents.

作者信息

El Sagheer Ghada M, Ahmad Asmaa K, Abd-ElFattah Aliaa S, Saad Zienab M, Hamdi Lamia

机构信息

Internal Medicine Department, Endocrinology Unit,

Hepatology Department.

出版信息

Clin Exp Gastroenterol. 2018 Oct 24;11:415-422. doi: 10.2147/CEG.S173484. eCollection 2018.

Abstract

BACKGROUND

Fibroblast growth factor (FGF) 21 was reported to be induced by different injurious agents, including chronic hepatitis C (CHC) virus, affecting the liver. The aims of this study were to evaluate the FGF21 levels in CHC patients before and after the treatment with direct-acting antiviral agents (DAAs) in comparison to that in control subjects and to correlate these levels with insulin resistance (IR), lipid profile, and fibrosis stages.

PATIENTS AND METHODS

We studied 75 naive CHC patients and 40 age- and gender-matched healthy control subjects. Patients were divided into five groups based on the severity of fibrosis as detected by Fibroscan as follows: F0, n=2; F1, n=13; F2, n=23; F3, n=16; F4, n=21. We estimated the FGF21 levels at the start of the study for all the participants and for the patients only at the end of treatment with simisipivir (SIM) and sofosbuvir (SOF). These levels were compared between the patients and the control subjects and also for the patients before and after the treatment with DAAs. The FGF21 levels were correlated to IR, lipid profile, and stages of liver fibrosis

RESULTS

The FGF21, fasting blood sugar (FBS), fasting insulin, and homeostasis model of IR (HOMA-IR) were significantly higher in CHC patients compared to control (5.04±0.75 vs 4.7±0.52, 20.15±5.13 vs 13.15±4.2, 4.49±1.28 vs 2.72±0.87, and 123.7±52.6 vs 21.8±8.8; ≤0.01, ≤0.001, ≤0.001, and ≤0.001, respectively). The posttreatment FGF21 levels were significantly reduced when compared to the pretreatment levels (123.7±52.5 vs 60.5±32.7, ≤0.001). FGF21 levels showed significant negative correlation with FBS and positive correlation with serum albumin (≤0.05 and ≤0.003, respectively). The multiple linear regression analysis revealed that serum albumin, high-density lipoprotein cholesterol (HDL-c), and the stage of liver fibrosis were independent risk factors for FGF21.

CONCLUSION

Besides its metabolic modulator role, FGF21 strongly introduced itself as a novel biomarker of hepatic injury in Egyptian, genotype-4, CHC patients.

摘要

背景

据报道,成纤维细胞生长因子(FGF)21可由包括慢性丙型肝炎(CHC)病毒在内的不同损伤因子诱导产生,影响肝脏。本研究的目的是评估直接抗病毒药物(DAA)治疗前后CHC患者的FGF21水平,并与对照组进行比较,同时将这些水平与胰岛素抵抗(IR)、血脂谱和纤维化分期相关联。

患者与方法

我们研究了75例初治CHC患者和40例年龄及性别匹配的健康对照者。根据Fibroscan检测到的纤维化严重程度,将患者分为五组:F0组,n = 2;F1组,n = 13;F2组,n = 23;F3组,n = 16;F4组,n = 21。我们在研究开始时对所有参与者以及仅在使用西米普韦(SIM)和索磷布韦(SOF)治疗结束时对患者进行FGF21水平评估。将这些水平在患者与对照者之间进行比较,同时也在DAA治疗前后的患者之间进行比较。FGF21水平与IR、血脂谱和肝纤维化分期相关。

结果

与对照组相比,CHC患者的FGF21、空腹血糖(FBS)、空腹胰岛素和IR稳态模型评估(HOMA-IR)显著更高(分别为5.04±0.75 vs 4.7±0.52、20.15±5.13 vs 13.15±4.2、4.49±1.28 vs 2.72±0.87以及123.7±52.6 vs 21.8±8.8;P≤0.01、P≤0.001、P≤0.001和P≤0.001)。与治疗前水平相比,治疗后FGF21水平显著降低(123.7±52.5 vs 60.5±32.7;P≤0.001)。FGF21水平与FBS呈显著负相关,与血清白蛋白呈正相关(分别为P≤0.05和P≤0.003)。多元线性回归分析显示,血清白蛋白、高密度脂蛋白胆固醇(HDL-c)和肝纤维化分期是FGF21的独立危险因素。

结论

除了其代谢调节作用外,FGF21在埃及基因4型CHC患者中强有力地表明自身是肝损伤的一种新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d74/6204854/6623c07d366b/ceg-11-415Fig1.jpg

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