Lemoine M, Chevaliez S, Bastard J P, Fartoux L, Chazouillères O, Capeau J, Pawlotsky J M, Serfaty L
Service d'Hépatologie, APHP, Hôpital Saint-Antoine, Paris, France.
UPMC Université Paris 06, UMR_S938, Paris, France.
J Viral Hepat. 2015 Nov;22(11):890-6. doi: 10.1111/jvh.12408. Epub 2015 Mar 26.
TNFα has been shown to play a role in hepatitis C virus (HCV)-induced insulin resistance (IR). Polymorphism of the IL28B gene that encodes IFN-lambda 3 may be associated with IR through modulation of TNFα. The aim of this study was to investigate the relationship between IL28B rs12979860 genotype, the level of TNFα activation and the degree of IR in patients with chronic hepatitis C. One hundred and thirty-three nondiabetic genotype 1 HCV-infected patients with biopsy proven noncirrhotic hepatitis C were investigated for IR (using HOMA index), IL28B rs12979860 genotype and fasting circulating levels of soluble receptor 1 of TNFα (sTNFR1) and adipokines: leptin, adiponectin and IL-6. The HOMA-IR was positively correlated with serum levels of leptin (r = 0.35, P < 0.0001) and sTNFR1 (r = 0.35, P < 0.0001) but not with IL-6 or adiponectin. IL28B rs12979860 CC genotype was observed in 35% patients. Genotype CC and nongenotype CC patients were similar in terms of HOMA-IR (means 1.6 ± 0.9 vs 1.7 ± 1.4) and had similar circulating levels of sTNFR1 and adipokines. Independent factors associated with IR were ferritin (OR = 1.002, P = 0.02), leptin (OR = 1.06, P = 0.02) and sTNFR1 (OR = 7.9, P = 0.04). This study suggests that in nondiabetic, noncirrhotic, HCV genotype 1-infected patients, there is no relationship between IL28B rs12979860 genotype and HOMA-IR or sTNFR1 level. HCV-related IR may be mediated through TNFα independent of IL28B genotype.
肿瘤坏死因子α（TNFα）已被证明在丙型肝炎病毒（HCV）诱导的胰岛素抵抗（IR）中起作用。编码干扰素λ3的IL28B基因的多态性可能通过调节TNFα与IR相关。本研究的目的是探讨慢性丙型肝炎患者中IL28B rs12979860基因型、TNFα激活水平与IR程度之间的关系。对133例经活检证实为非肝硬化性丙型肝炎的非糖尿病基因型1 HCV感染患者进行了IR（采用HOMA指数）、IL28B rs12979860基因型以及空腹循环中TNFα可溶性受体1（sTNFR1）和脂肪因子（瘦素、脂联素和IL-6）水平的检测。HOMA-IR与血清瘦素水平（r = 0.35，P < 0.0001）和sTNFR1水平（r = 0.35，P < 0.0001）呈正相关，但与IL-6或脂联素无关。35%的患者观察到IL28B rs12979860 CC基因型。CC基因型患者和非CC基因型患者在HOMA-IR方面相似（均值分别为1.6±0.9和1.7±1.4），且sTNFR1和脂肪因子的循环水平相似。与IR相关的独立因素为铁蛋白（OR = 1.002，P = 0.02）、瘦素（OR = 1.06，P = 0.02）和sTNFR1（OR = 7.9，P = 0.04）。本研究表明，在非糖尿病、非肝硬化、基因型1 HCV感染患者中，IL28B rs12979860基因型与HOMA-IR或sTNFR1水平之间无关联。HCV相关的IR可能通过TNFα介导，独立于IL28B基因型。
