A serum metabonomics study on the difference between alcohol- and HBV-induced liver cirrhosis by UPLC coupled with Q-TOF mass spectrometry

Background Liver cirrhosis is the fatal sequel of chronic hepatitis, making early diagnosis of liver cirrhosis critical. Liver biopsy is still the standard diagnostic method for liver cirrhosis, although its use in a wide population with alcoholism or HBV infection remains difficult. In this study, we used the metabonomic approach to detect potential biomarkers for early diagnosis of liver cirrhosis. Methods Serums were collected prospectively from normal control subjects (n=22) and patients with alcoholic cirrhosis (n=18) or hepatitis B virus (HBV)-induced cirrhosis (n=19). The serum metabonome was analyzed using ultraperformance liquid chromatography (LC)/time-of-flight mass spectrometry (MS) integrated with chemometrics. The acquired LC-MS data were normalized and processed using principal component analysis and partial least squares discrimination analysis. Results Significant differences in the metabonome among the three groups were observed. Lysophosphatidyl cholines (LPCs) (LPC C16:0, LPC C18:0, LPC C18:2, LPC C18:3, LPC C20:3, LPC C20:5) decreased in the serum of patients with hepatic cirrhosis, whereas bile acids (glycocholic acid, glycochenodeoxycholic acid), hypoxanthine, and stearamide increased in the serum of patients with liver cirrhosis. These metabolites are considered “common” biomarkers for hepatic cirrhosis. Oleamide and myristamide increased in the serum of patients with alcoholic cirrhosis but decreased in those with HBV-induced cirrhosis. These could be specific biomarkers for differential diagnosis between alcohol- and HBV-induced hepatic cirrhosis. Conclusions There are significance metabonomic differences between alcohol- and HBV-induced liver cirrhosis. This study demonstrates that metabonomics is a top-down system biology tool for conducting research on clinical problems.     

乙型肝炎慢加急性肝衰竭前期的临床特征及预后评分模型的建立

目的探讨乙型肝炎相关慢加急性肝衰竭(HBV-ACLF)前期患者的临床特征,并建立相应的预后评分模型。方法利用HBV-ACLF中国诊断标准研究(COSSH-ACLF)队列,回顾性分析725例乙型肝炎相关慢加急性肝功能障碍(HBV-ACHD)患者的临床特征,采用多因素COX回归分析90 d预后的相关独立危险因素并建立预后评分模型,并利用内部500例和外部390例HBV-ACHD患者进行验证。结果在725例HBV-ACHD患者中,男性为主(76.8%),96.8%患者有肝硬化基础,并发症以腹水(66.5%)多见,器官衰竭以凝血功能衰竭(4.1%)为主,90 d病死率为9.2%。多因素COX回归分析得出,总胆红素(TBil)、白细胞计数(WBC)、碱性磷酸酶(ALP)是HBV-ACHD患者90 d病死率的最佳预测指标,并建立评分模型COSSH-ACHDs=0.75×ln(WBC)+0.57×ln(TBil)-0.94×ln(ALP)+10,其受试者工作特征曲线下面积(auROC)显著高于终末期肝病模型(MELD)、MELD-Na、CTP及CLIF-C ADs(P<0.05),500例内部随机选择组和390例外部验证组均验证了类似结果。结论HBV-ACHD患者是一组以肝硬化失代偿为主、合并少量器官衰竭的人群,其90 d病死率为9.2%,COSSH-ACHDs具有更高的预测HBV-ACHD患者90 d预后的效能,为临床早期诊治提供循证医学依据。