Gut: 1型慢丙肝者SVR减轻胰岛素抵抗

Gut杂志［Gut 2012，61（1）：128］发表研究：1型慢性丙型肝炎患者持续病毒学应答（SVR）与稳态模型评估法—胰岛素抵抗（HOMA-IR）减轻有关，2/3型患者无此情况。基因1型HCV可能对IR的发生有直接作用，而不依赖于机体的代谢因素。

原始文献：

Thompson AJ, Patel K, Chuang WL, Lawitz EJ, Rodriguez-Torres M, Rustgi VK, Flisiak R, Pianko S, Diago M, Arora S, Foster GR, Torbenson M, Benhamou Y, Nelson DR, Sulkowski MS, Zeuzem S, Pulkstenis E, Subramanian GM, McHutchison JG; ACHIEVE-1 and ACHIEVE-2/3 Study Teams.Viral clearance is associated with improved insulin resistance in genotype 1 chronic hepatitis C but not genotype 2/3.Gut. 2012 Jan;61(1):128-34.

OBJECTIVES:

Genotype-specific associations between hepatitis C virus (HCV) and insulin resistance (IR) have been described, but a causal relationship remains unclear. This study investigated the association between a sustained virological response (SVR) and IR after chronic HCV therapy.

METHODS:

2255 treatment-naive patients with chronic HCV genotype 1 or 2/3 were enrolled in two phase 3 trials of albinterferon alpha-2b versus pegylated interferon alpha-2a for 48 or 24 weeks, respectively. IR was measured before treatment and 12 weeks after treatment using homeostasis model assessment (HOMA)-IR.

RESULTS:

Paired HOMA-IR measurements were available in 1038 non-diabetic patients (497 with genotype 1; 541 with genotype 2/3). At baseline the prevalence of HOMA-IR >3 was greater in patients with genotype 1 than 2/3 (33% vs 27%; p=0.048). There was a significant reduction in the prevalence of IR in patients with genotype 1 achieving SVR (δ 10%; p<0.001), but not in genotype 1 non-responders or those with genotype 2/3. Multivariate analysis indicated that SVR was associated with a significant reduction in mean HOMA-IR in patients with genotype 1 (p=0.004), but not in those with genotype 2/3, which was independent of body mass index, alanine transaminase, γ-glutamyl transpeptidase and lipid level changes.

CONCLUSIONS:

SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.

拓展阅读：

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• Gut: 1型慢丙肝者SVR减轻胰岛素抵抗
• PNAS：丙肝病毒通过劫持肝脏microRNA以幸存
• Nat.Med：抑制NPC1L1表达或可预防丙肝病毒感染
• 2011年AASLD基因1型丙肝治疗指南更新（附全文）
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