Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, 93053 Regensburg, Germany.
Department of Internal Medicine I, University Hospital Regensburg, 93053 Regensburg, Germany.
Int J Mol Sci. 2022 Aug 29;23(17):9806. doi: 10.3390/ijms23179806.
Hepatitis C virus (HCV) infection affects ceramide metabolism, and, here, we have evaluated associations of eight serum ceramide species with viral load, viral genotype, and disease markers in 178 patients with chronic HCV. In this cohort, ceramide d18:1;O2/16:0 was higher in the serum of the 20 diabetic patients compared to the patients without this complication. Moreover, ceramide d18:1;O2/24:0 was negatively correlated with age. Of note, all but ceramide d18:1;O2/16:0 and 26:0 were diminished in the serum of patients with liver cirrhosis and, with the exception of ceramide d18:1;O2/16:0, were negatively correlated with the model for end-stage liver disease (MELD) score. Most of the serum ceramides are carried in low-density lipoprotein (LDL), which rises following effective direct-acting antiviral (DAA) therapy. Ceramide d18:1;O2/24:0 recovered in parallel with LDL, whereas ceramide d18:1;O2/18:0 declined. Genotype-3-infected patients had the lowest ceramide levels, which were comparable to other genotypes after DAA treatment. Notably, ceramide d18:1;O2/23:0 and 24:0 were negatively correlated with the MELD score in patients with liver cirrhosis at the end of DAA therapy. Long-chain (LC) ceramides show adverse effects, whereas very-long-chain (VL) species have protective functions in the liver. The ratio of VL/LC ceramides was higher in non-cirrhosis patients than cirrhosis patients and further increased at the end of therapy in this subgroup. In summary, our study shows that serum ceramide levels are related to liver cirrhosis and viral genotype. Whether the more favorable serum ceramide profile in non-cirrhosis patients, before and after DAA therapy, is of pathophysiological importance needs further investigation.
丙型肝炎病毒 (HCV) 感染会影响神经酰胺代谢，在这里，我们评估了 178 例慢性 HCV 患者的八种血清神经酰胺与病毒载量、病毒基因型和疾病标志物之间的相关性。在这个队列中，20 例糖尿病患者的血清中神经酰胺 d18:1;O2/16:0 高于无此并发症的患者。此外，神经酰胺 d18:1;O2/24:0 与年龄呈负相关。值得注意的是，除了神经酰胺 d18:1;O2/16:0 和 26:0 之外，所有血清神经酰胺在肝硬化患者的血清中均减少，除了神经酰胺 d18:1;O2/16:0 之外，还与终末期肝病模型 (MELD) 评分呈负相关。大多数血清神经酰胺都存在于低密度脂蛋白 (LDL) 中，在有效的直接作用抗病毒 (DAA) 治疗后，LDL 会升高。神经酰胺 d18:1;O2/24:0 与 LDL 一起恢复，而神经酰胺 d18:1;O2/18:0 则下降。感染基因型 3 的患者的神经酰胺水平最低，在 DAA 治疗后与其他基因型相当。值得注意的是，在 DAA 治疗结束时，肝硬化患者的神经酰胺 d18:1;O2/23:0 和 24:0 与 MELD 评分呈负相关。长链 (LC) 神经酰胺有不良影响，而非常长链 (VL) 神经酰胺在肝脏中有保护作用。非肝硬化患者的 VL/LC 神经酰胺比值高于肝硬化患者，在该亚组中，在治疗结束时进一步增加。综上所述，我们的研究表明，血清神经酰胺水平与肝硬化和病毒基因型有关。在 DAA 治疗前后，非肝硬化患者的血清神经酰胺谱更有利是否具有病理生理意义，还需要进一步研究。
