Apolipoprotein-E and hepatitis C lipoviral particles in genotype 1 infection: Evidence for an association with interferon sensitivity

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• 作者：David A. Sheridan¹ ; ^{david.sheridan@ncl.ac.uk} ; Simon H. Bridge¹ ; Daniel J. Felmlee¹ ; Mary M.E. Crossey² ; Howard C. Thomas² ; Simon D. Taylor-Robinson² ; Geoffrey L. Toms¹ ; R. Dermot G. Neely³ ; Margaret F. Bassendine¹
• 关键词：apoE ; apolipoprotein E ; HCV ; hepatitis C virus ; LVP ; lipoviral particles ; apoB ; apolipoprotein B ; EVR ; early virological response ; VLDL ; very-low-density-lipoprotein ; TRL ; triglyceride-rich lipoprotein ; LDL ; low-density-lipoprotein ; IP10 ; interferon gamma
• 刊名：Journal of Hepatology
• 出版年：2012
• 期刊代码：162_01688278
• 类别：med
• 出版时间：July, 2012
• 卷：57
• 期：1
• 页码：32-38
• 文件大小：810 K

摘要

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Background & Aims

Hepatitis C virus (HCV) interacts with apolipoproteins B (apoB) and E (apoE) to form infectious lipoviral particles (LVP). Response to peginterferon is influenced by interferon-stimulated genes (ISGs) and <em>IL28Bem> genotype. LDL cholesterol (LDL-C) also predicts interferon response, therefore we hypothesised that LVP may also be associated with interferon sensitivity.

Methods

LVP (HCV RNA density 猢?.07 g/ml) and 鈥榥on-LVP鈥?(d >1.07 g/ml) were measured in 72 fasted HCV-G1 patients by iodixanol density gradient ultracentrifugation and the LVP ratio (LVP/LVP + non-LVP) was calculated. Fasting lipid profiles and apolipoproteins B and E were measured. Interferon-gamma-inducible protein 10 kDa (IP10), a marker of ISGs, was measured by ELISA.

Results

Complete early virological response (EVR) was associated with lower apoE (23.9 卤 7.7 <em>vs.em> 36.1 卤 15.3 mg/L, <em>pem> = 0.013), higher LDL-C (<em>pem> = 0.039) and lower LVP ratios (<em>pem> = 0.022) compared to null responders. In multivariate linear regression analysis, apoE was independently associated with LVP (R² 19.5%, <em>pem> = 0.003) and LVP ratio (<em>pem> = 0.042), and negatively with LDL-C (<em>pem> <0.001). IP10 was significantly associated with ApoB (<em>pem> = 0.001) and liver stiffness (<em>pem> = 0.032). <em>IL28Bem> rs12979860 CC was associated with complete EVR (<em>pem> = 0.044), low apoE (CC 28 卤 11 <em>vs.em> CT/TT 35 卤 13 mg/L, <em>pem> = 0.048) and higher non-LVP (<em>pem> = 0.008). Logistic regression analysis indicated that patients with high LVP ratios were less likely to have EVR (odds ratio 0.01, <em>pem> = 0.018).

Conclusions

In HCV-G1, interferon sensitivity is characterised by low LVP ratios and low apoE levels in addition to higher LDL-C and <em>IL28Bem> rs12979860 CC. Null-response is associated with increased LVP ratio. The association of apoE and LVP with peginterferon treatment response suggests that lipid modulation is a potential target to modify interferon sensitivity.