A Serum Metabonomics Study Of Hepatitis C Virus Spontaneous Clearance Patients

Hepatitis C is a serious threat to global public health diseases, there is no effectivevaccine can prevent. It is estimated that about180million people worldwide infected withHCV, mainly through blood products transfusion, broken skin and mucous membrane, andother ways. In the HCV acute infection populations about20%to30%can be achieved thatthe virus be spontaneously cleared. After6months, the HCV virus has not cleared wereknown as chronic hepatitis C virus infection, about50%to80%of HCV infection willprogress to chronic condition, in which20%to30%patients will develop liver cirrhosis orhepatocellular carcinoma. Currently the standard treatment for hepatitis C therapy ispegylated interferon in combination with ribavirin (PEG-IFN-α/RBV). Due to the longcourse of treatment, adverse reactions, the relatively high price of pegylated interferon andthe low rate of sustained virologic respons, the treatment of patients is a greater burden.Metabolomics derived from metabolic profiling analysis, as a new research method, hasbecome the important part of systems biology, mainly reflecting the the metabolitescorresponding changes in external stimuli caused by the change of the pathophysiology ofthe tissue cells. Metabolomics study focus on the small molecules in a biological sample,which has a molecular weight often less than1000Da. The change of metabolic componentsof the biological sample completely could be found by the research technology.30persons were chosen in each group of this study， It based on the serummetabonomics were analyzed with LC-MS/MS in each group, and then pattern recognitionof principal component analysis (PCA) and orthogonal partial least squares discriminantanalysis (OPLS-DA) was performed to discover different metabolites. According to the VIP(variable importance in projection) value, non-parametric test and identifying in thedatabases, a number of potential biomarkers which were differences among the three groupsof serum metabolites were screened out.The research found that there are twenty-five variables were significant differencesamong the three groups. By correlation analysis and structural identification, seven variableswere identified as Arachidonic acid, Palmitoleic acid, Dodecanoylcarnitine, LysoPC(20:5(5Z,8Z,11Z,14Z,17Z)), LysoPC(16:0), LysoPE(18:0), LysoPE(16:0/0:0) whichrelate to fatty acid metabolism and pholipids catabolism. Especially, Arachidonic acid andsome variables whose structure were not identified clearly such as m/z179.0719, m/z382.1360, m/z548.3475, m/z680.4281and m/z303.2323show better predictability for thehepatitis C spontaneous clearance group and their area under the curve (AUC) were from0.887to0.977. They have quite good specificity and sensitivity.Significant differences existed among three groups on the serum metabolic level.Clinical outcomes of HCV infection may be related with these metabolites in serum.