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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Variations in Serum Sphingolipid Levels Associate With Liver Fibrosis Progression and Poor Treatment Outcome in Hepatitis C Virus but Not Hepatitis B Virus Infection
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Variations in Serum Sphingolipid Levels Associate With Liver Fibrosis Progression and Poor Treatment Outcome in Hepatitis C Virus but Not Hepatitis B Virus Infection

机译：丙型肝炎病毒而非乙型肝炎病毒感染的血清鞘脂水平变化与肝纤维化进展和治疗效果差相关

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摘要

Ablation of very-long-chain ceramides (Cers) with consecutive elevations in sphinganine levels has been shown to cause a severe hepatopathy in a knockout mouse model. We have recently shown that serum sphingolipids (SLs) are deregulated in patients with chronic liver disease. However, their role as possible biomarkers in liver fibrosis remains to date unexplored. We assessed, using liquid chromatography/tandem mass spectrometry, serum concentrations of various SL metabolites in 406 patients with chronic viral hepatitis, 203 infected with genotype 1 hepatitis C virus (HCV) and 203 with hepatitis B virus (HBV), respectively. We observed significant variations of serum SLs, with sphingosine and sphinganine being, both in univariate (P<0.05) as well as in multivariate analysis, significantly associated to severity of liver fibrosis in HCV-infected patients (odds ratio [OR]: 1.111; confidence interval [CI]: 1.028-1.202; P=0.007 and OR, 0.634; CI, 0.435-0.925; P=0.018, respectively). Serum SLs correlated significantly with serum triglyceride and cholesterol levels as well as with insulin resistance, defined by the homeostatic model assessment index, in HCV patients. Sustained viral response rates in HCV patients were independently predicted by serum C24Cer (OR, 0.998; CI, 0.997-0.999; P=0.001), its unsaturated derivative C24:1Cer (OR, 1.001; CI, 1.000-1.002; P=0.059), and C18:1Cer (OR, 0.973; CI, 0.947-0.999; P=0.048), together with ferritin (OR, 1.006; CI, 1.003-1.010; P<0.001), alkaline phosphatase (OR, 1.020; CI, 1.001-1.039; P=0.032), and interleukin-28B genotype (OR, 9.483; CI, 3.139-28.643; P<0.001). Conclusion: Our study demonstrates a tight interaction between variations in serum SL levels and progression of liver fibrosis as well as responsiveness to antiviral therapy. Particularly, sphingosine, sphinganine, and C24Cer appear as promising novel biomarkers in chronic HCV infection and should be further evaluated within the noninvasive prediction of liver fibrosis. (Hepatology 2015;61:812-822)
机译：已证明，在剔除小鼠模型中，鞘氨醇水平持续升高的超长链神经酰胺（Cers）消融会导致严重的肝病。我们最近显示，慢性肝病患者的血清鞘脂（SL）失调。然而，迄今为止，它们作为肝纤维化中可能的生物标志物的作用尚待探索。我们使用液相色谱/串联质谱法分别评估了406例慢性病毒性肝炎，203例基因1型丙型肝炎病毒（HCV）和203例B型肝炎病毒（HBV）患者的各种SL代谢产物的血清浓度。我们在单变量（P <0.05）和多变量分析中均观察到血清SLs，鞘氨醇和鞘氨醇存在显着差异，与HCV感染患者的肝纤维化严重程度显着相关（优势比[OR]：1.111;置信区间[CI]：1.028-1.202; P = 0.007; OR：0.634; CI：0.435-0.925; P = 0.018）。 HCV患者的血清SL与血清甘油三酸酯和胆固醇水平以及由稳态模型评估指数定义的胰岛素抵抗密切相关。血清C24Cer（OR，0.998; CI，0.997-0.999; P = 0.001），其不饱和衍生物C24：1Cer（OR，1.001; CI，1.000-1.002; P = 0.059）独立预测HCV患者的持续病毒应答率和C18：1Cer（OR，0.973; CI，0.947-0.999; P = 0.048），以及铁蛋白（OR，1.006; CI，1.003-1.010; P <0.001），碱性磷酸酶（OR，1.020; CI，1.001） -1.039; P = 0.032）和白介素28B基因型（OR，9.483; CI，3.139-28.643; P <0.001）。结论：我们的研究表明血清SL水平的变化与肝纤维化进程以及对抗病毒治疗的反应性之间存在紧密的相互作用。特别地，鞘氨醇，鞘氨醇和C24Cer在慢性HCV感染中似乎是有希望的新型生物标志物，应在肝纤维化的非侵入性预测范围内进一步评估。 （肝病2015; 61：812-822）

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