Li Jun-Feng, Qu Feng, Zheng Su-Jun, Ren Feng, Wu Hui-Li, Liu Mei, Ren Jin-Yu, Chen Yu, Duan Zhong-Ping, Zhang Jin-Lan
The First Clinical Medical School, Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China.
Mol Med Rep. 2015 Jul;12(1):323-30. doi: 10.3892/mmr.2015.3361. Epub 2015 Feb 17.
The plasma profile of sphingolipids in hepatic fibrosis patients with chronic hepatitis C (CHC) is rarely considered at present. The association between plasma sphingolipids and severe fibrosis in CHC remains an obscure area of research. The aim of the present study was to assess the plasma profile of sphingolipids and to examine the association between plasma sphingolipids and severe fibrosis in CHC, in order to identify potential novel markers of severe fibrosis in CHC. A cohort of 120 treatment-naïve patients with CHC were included in the present study. Liver biopsies were performed and routine serological indicators were measured. Plasma sphingolipids were detected using high performance liquid chromatography tandem mass spectrometry. A total of 44 plasma sphingolipids were detected. Plasma hexosylceramide (HexCer; d18:1/12:0), HexCer (d18:1/16:0) and HexCer (d18:1/22:0) were shown to be significantly different in patients with CHC between those with and without severe fibrosis (Metavir F ≥ 3; P < 0.05). HexCer (d18:1/12:0) was observed to be closely associated with severe fibrosis in CHC [odds ratio (OR)=1.03] following adjustment for confounding variables in a multivariate analysis. HexCer (d18:1/12:0) had diagnostic value for severe fibrosis in CHC [area under the curve (AUC)=0.69]. In patients with CHC who had developed significant fibrosis (Metavir F ≥ 2), HexCer (d18:1/12:0) remained closely associated with severe fibrosis (OR=1.08) in this subgroup. In addition, HexCer (d18:1/12:0) had sufficient diagnostic ability (AUC=0.73) to distinguish severe fibrosis in patients with CHC with significant fibrosis. In conclusion, the present study indicated that plasma HexCer (d18:1/12:0) exhibits a close correlation with severe hepatic fibrosis in CHC, particularly in patients who have significant fibrosis. Additionally, HexCer (d18:1/12:0) may be a potential marker of severe hepatic fibrosis in CHC.
目前很少考虑慢性丙型肝炎(CHC)肝纤维化患者的血浆鞘脂谱。CHC患者血浆鞘脂与严重纤维化之间的关联仍是一个研究模糊的领域。本研究的目的是评估血浆鞘脂谱,并研究CHC患者血浆鞘脂与严重纤维化之间的关联,以确定CHC严重纤维化的潜在新标志物。本研究纳入了120例未经治疗的CHC患者队列。进行了肝活检并测量了常规血清学指标。使用高效液相色谱串联质谱法检测血浆鞘脂。共检测到44种血浆鞘脂。CHC患者中,有严重纤维化(Metavir F≥3)和无严重纤维化的患者之间,血浆己糖神经酰胺(HexCer;d18:1/12:0)、HexCer(d18:1/16:0)和HexCer(d18:1/22:0)存在显著差异(P<0.05)。在多变量分析中对混杂变量进行校正后,观察到HexCer(d18:1/12:0)与CHC中的严重纤维化密切相关[比值比(OR)=1.03]。HexCer(d18:1/12:0)对CHC中的严重纤维化具有诊断价值[曲线下面积(AUC)=0.69]。在已发生显著纤维化(Metavir F≥2)的CHC患者中,该亚组中HexCer(d18:1/12:0)仍与严重纤维化密切相关(OR=1.08)。此外,HexCer(d18:1/12:0)具有足够的诊断能力(AUC=0.73)来区分有显著纤维化的CHC患者中的严重纤维化。总之,本研究表明,血浆HexCer(d18:1/12:0)与CHC中的严重肝纤维化密切相关,尤其是在有显著纤维化的患者中。此外,HexCer(d18:1/12:0)可能是CHC严重肝纤维化的潜在标志物。