乙型/丙型肝炎肝硬化患者外周血清鞘脂表达谱特征分析

Expression profiles of sphingolipids in peripheral serum in patients with hepatitis B/C cirrhosis

目的探索乙型/丙型肝炎肝硬化与非病毒性肝硬化患者外周血清鞘脂的不同表达谱特征。方法选取2014年7月-2015年5月首都医科大学附属北京佑安医院疑难肝病及人工肝中心收治的104例肝硬化患者为研究对象,最终纳入97例肝硬化患者,其中包括66例(68.04%)乙型/丙型肝炎肝硬化及31例(31.96%)非病毒性肝硬化患者。采用高效液相色谱-质谱分析法检测患者外周血清中57种鞘脂的表达水平,计量资料两组间比较采用t检验或Mann-Whitney U检验。计数资料两组间比较采用χ^2检验。单因素分析结果中有意义的变量纳入logistic多因素回归分析。结果两组患者年龄、男性比例、TBil、DBil及GGT等临床指标之间差异均无统计学意义(P值均>0.05)。检测57种血清鞘脂表达中,Cer(d18∶1/12∶0)、HexCer(d18∶1/14∶1)和dhCer(d18∶0/24∶1)-1-P在病毒性肝炎肝硬化组的表达水平分别为168.61(168.54~168.88)pmol/0.1 ml、213.93(211.15~218.92)pmol/0.1 ml、60.07(59.40~61.23)pmol/0.1ml,均高于非病毒性肝硬化组[168.53(168.48~168.63)pmol/0.1ml、212.26(209.90~214.64)pmol/0.1 ml、59.42(59.28~59.87)pmol/0.1 ml],两组间差异均有统计学意义(Z值分别为-2.54、-2.03、-2.32,P值均<0.05)。logistics回归分析结果表明,dhCer(d18∶0/24∶1)-1-P高表达与乙型/丙型肝炎肝硬化独立相关(比值比=1.11,95%可信区间1.004~1.225,P=0.042)。病毒性肝炎肝硬化患者亚组分析结果表明,Cer(d18∶1/12∶0)、HexCer(d18∶1/14∶1)和dhCer(d18∶0/24∶1)-1-P在乙型肝炎肝硬化和丙型肝炎肝硬化患者之间的表达水平差异均无统计学意义(Z值分别为-0.563、-0.610、-0.579,P值均>0.05)。结论外周血清鞘脂dhCer(d18∶0/24∶1)-1-P与乙型/丙型肝炎肝硬化密切相关,可能有助于从鞘脂角度深入理解病毒性肝硬化的疾病特征。

Objective To investigate the expression profiles of sphingolipids in peripheral serum in patients with hepatitis B/C cirrhosis and those with non-viral hepatitis-related cirrhosis.Methods A total of 104 patients with liver cirrhosis who were admitted to Difficult&Complicated Liver Diseases and Artificial Liver Center,Beijing YouAn Hospital,Capital Medical University,from July 2014 to May 2015 were enrolled as subjects,and finally 97 patients with liver cirrhosis were enrolled,among whom there were 66 patients(68.04%)with hepatitis B/C cirrhosis and 31 patients(31.96%)with non-viral hepatitis-related cirrhosis.High-performance liquid chromatography-mass spectrometry was used to measure the expression of 57 sphingolipids in peripheral serum.The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The variables with statistical significance in the univariate analysis were included in the multivariate analysis.Results There were no significant differences between the two groups in age,proportion of male patients,total bilirubin,direct bilirubin,and gamma-glutamyl transpeptidase(all P>0.05).As for the 57 sphingolipids in peripheral serum,compared with the non-viral hepatitis-related cirrhosis group,the viral hepatitis-related cirrhosis group had significantly higher expression of Cer(d18∶1/12∶0)[168.61(168.54-168.88)pmol/0.1 ml vs 168.53(168.48-168.63)pmol/0.1 ml,Z=-2.54,P<0.05],HexCer(d18∶1/14∶1)[213.93(211.15-218.92)pmol/0.1 ml vs 212.26(209.90-214.64)pmol/0.1 ml,Z=-2.03,P<0.05],and dhCer(d18∶0/24∶1)-1-P[60.07(59.40-61.23)pmol/0.1 ml vs 59.42(59.28-59.87)pmol/0.1 ml,Z=-2.32,P<0.05].The logistic regression analysis revealed that high expression of dhCer(d18∶0/24∶1)-1-P was independently associated with hepatitis B/C cirrhosis(odds ratio=1.11,95%confidence interval:1.004-1.225,P=0.042).The subgroup analysis of the patients with viral hepatitis-associated cirrhosis showed that there were no significant differences between the patients with hepatitis B cirrhosis and those with hepatitis C cirrhosis in the expression of Cer(d18∶1/12∶0),HexCer(d18∶1/14∶1),and dhCer(d18∶0/24∶1)-1-P(Z=-0.563,-0.610,and-0.579,all P>0.05).Conclusion The sphingolipid dhCer(d18∶0/24∶1)-1-P in peripheral serum is closely associated with hepatitis B/C cirrhosis and may help to understand the features of viral hepatitis-related cirrhosis from the perspective of sphingolipids.