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通过直接作用抗病毒药物清除丙型肝炎病毒后对葡萄糖代谢和胰岛素抵抗的调节

Modulation of glucose metabolism and insulin resistance following hepatitis C virus clearance via direct-acting antivirals.

作者信息

Jabeen Sajida, Khan Ramsha, Alrashed May M, Ullah Sajjad, Nabi Ghulam, Ullah Malik Ihsan, Waqar Ahmed Bilal, Attia Kotb A, Kimiko Itoh

机构信息

Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan.

University Institute of Medical Lab Technology, The University of Lahore, Lahore, Pakistan.

出版信息

Sci Rep. 2025 Apr 26;15(1):14663. doi: 10.1038/s41598-025-97827-1.

Abstract

The positive sense RNA virus, hepatitis C virus (HCV), is affiliated with the Flaviviridae family. Approximately 1% of people around the globe experience the impact of the HCV, which can coax them into potentially fatal conditions, including cirrhosis and carcinoma. The second-highest hepatitis C infection burden lies in Pakistan. The case of a HCV-infected patient who additionally has obesity or concurrent medical conditions like diabetes, HBV infection, or HIV infection is susceptible to becoming direr. Direct-acting antiviral medications replaced interferons as a staple of the treatment plan since they have fewer, milder side effects and a higher SVR rate in patients. The present study sought to assess the modifications to glucose homeostasis in non-diabetic chronic HCV-infected patients getting DAA treatment and the factors that independently pertain to insulin resistance. The study enrolled 250 patients, with 190 individuals having HCV-positive PCR results. The analysis included CBC, LFTs, glycaemic and insulin measurements, and the insulin resistance index calculation. Key cardiometabolic risk factors crucial for defining MASLD were assessed, including BMI measurement, evaluation of type 2 diabetes, and lipid profile analysis. The same tests were repeated following DAA therapy, and HOMA-IR was computed to compare pre-and post-treatment results. Among the 250 recruited patients, 190 were detected as HCV positive by the PCR assay, 57% (110 patients) were women, 43% (80 patients) were men, and patients were 47 years old on average. The patients showed high BMI (average 26.28 kg/m) and signs of severe insulin resistance (HOMA-IR > 2.5). Multivariable logistic regression analysis pointed out that elevated baseline levels of triglycerides, ALT, ALP, cholesterol, and total bilirubin were independently associated with high insulin resistance. A notable improvement in HOMA-IR from 13.63 ± 2.63 to 3.16 ± 1.52 (p < 0.005) was spotted after administering interferon-free antiviral therapy for 3 months. The presence of high BMI, hyperlipidemia, and elevated levels of ALP, ALT, and AST in non-diabetic HCV-infected patients were independently associated with IR. In patients who previously had a higher IR index, there was a decrease in the HOMA-IR index after infection clearance by direct-acting antivirals.

摘要

正链RNA病毒丙型肝炎病毒(HCV)属于黄病毒科。全球约1%的人受到HCV的影响,这可能使他们陷入潜在的致命状况,包括肝硬化和癌症。丙型肝炎感染负担第二高的国家是巴基斯坦。HCV感染患者若同时患有肥胖症或并发糖尿病、HBV感染或HIV感染等疾病,病情可能会更严重。直接作用抗病毒药物已取代干扰素成为治疗方案的主要药物,因为其副作用更少、更轻,且患者的持续病毒学应答率更高。本研究旨在评估接受DAA治疗的非糖尿病慢性HCV感染患者的葡萄糖稳态变化以及与胰岛素抵抗独立相关的因素。该研究招募了250名患者,其中190人PCR结果显示HCV呈阳性。分析包括全血细胞计数、肝功能检查、血糖和胰岛素测量以及胰岛素抵抗指数计算。评估了对定义代谢相关脂肪性肝病至关重要的关键心脏代谢危险因素,包括体重指数测量、2型糖尿病评估和血脂谱分析。在DAA治疗后重复进行相同测试,并计算HOMA-IR以比较治疗前后的结果。在招募的250名患者中,PCR检测发现190人HCV呈阳性,57%(110名患者)为女性,43%(80名患者)为男性,患者平均年龄为47岁。患者体重指数较高(平均26.28kg/m)且有严重胰岛素抵抗迹象(HOMA-IR>2.5)。多变量逻辑回归分析指出,甘油三酯、ALT、ALP、胆固醇和总胆红素的基线水平升高与高胰岛素抵抗独立相关。在进行3个月的无干扰素抗病毒治疗后,发现HOMA-IR从13.63±2.63显著改善至3.16±1.52(p<0.005)。非糖尿病HCV感染患者中高体重指数、高脂血症以及ALP、ALT和AST水平升高与胰岛素抵抗独立相关。在先前胰岛素抵抗指数较高的患者中,通过直接作用抗病毒药物清除感染后,HOMA-IR指数有所下降。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/299c/12033326/9c77191a3f86/41598_2025_97827_Fig1_HTML.jpg

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