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A Metabonomics Study Of Chronic Hepatitis B In Different Stages Using HPLC/TripleTOF-MS/MS

Posted on:2013-02-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:X ShaoFull Text:PDF
GTID:1114330371982696Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Chronic hepatitis B virus (HBV) infection is a serious global public healthproblem, with approximately2billion people infected worldwide, and morethan3.5million people with chronic HBV infection. Hepatitis B carriers are athigh risk for development of liver fibrosis, cirrhosis, decompensation cirrhosisand hepatocellular carcinoma (HCC). Each year, about100million people diedof liver failure, cirrhosis and hepatocellular carcinoma which due to HBVinfection. In2006, the hepatitis B epidemiological survey in China showed thatour existing chronic HBV infection is9300million, of which patients withchronic hepatitis B is about20million. Which is infected by hepatitis B virus,the natural history of chronic hepatitis B (CHB) is divided into three(or four)phases, immune tolerant, immune active or immune clearance,inactive carrierand reactivation phase. Only the immune active phase is the best period ofantiviral treatment. But in different stages of infection of judgment there is nospecific biomarkers.The distinction between different stages mainly rely onserological, biochemical, virological, iconography tests and liver biopsy ofclinical evaluation. The patients refused to do liver biopsy as is an invasiveoperation, even though it to be the"gold standard" method in evaluating chronichepatitis and fibrosis. So effective methods for distinguish the different phasesare an urgent requirement for clinics, and chronic mechanism is not very clear,its treatment is still a major problem in the medical profession.Metabonomics is the second genomics, transcriptome and proteome after anew group of technology, is one of the indispensable basic discipline forsystems biology. Its object of study are the relative molecular mass smallmolecules less than1000Dalton. Compared with genomics and proteomics, metabolomics, and physiology more closely linked. The disease causes thebody the pathophysiological process of change, and ultimately lead to themetabolite change accordingly, through the analysis of certain metabolites, andcompared with normal metabolites to find disease biomarkers, will provide abetter disease diagnostic methods.The purpose of this study was to use metabonomic profiling to determinea potential specific biomarker pattern in micro-plasma and urine as a non-invasive infected by HBV in different periods detection.We used the HPLC/TripleTOF-MS/MS based human plasma and urinemetabolic profiling. Multidimensional statistical methods to find relateddifferences in metabolite able to distinguish between the different groups.3077and3100ions were detected in the initial screening experiments. By statisticalanalysis of148feature variables were significantly different between thedifferent groups.23important differential metabolites were found and wereconfirmed and related with pathophysiological process of hepatitis. Thepotential biomarkers in the hepatocyte damage and repair, energy consumption,fatty acid biosynthesis, bile acid biosynthesi and inflammation play animportant role in progression, and they also can be used for clinical staging ofindicators is not clear without liver biopsy. Such as glycocholic acid,Taurochenodeoxycholic acid, Taurocholic acid,3-Oxodecanoic acid, biliverdin,lysophosphatidylethanolamines and lysophosphatidylcholines could be used asclinical indicators of staging without liver biopsy, which could provide goodsensitivity and specificity for the diagnosis of immune active CHB.Lysophosphatidylcholines could be the potential biomarkers for immunetolerant and oleamide could be the potential biomarker of inactive carrier.This metabonomic approach may provide insight into discovery andidentification of new diagnostic biomarkers for immune active phase in chronichepatitis B and for guidance of antiviral treatment is of great significance. Drug treatment not only improves efficiency, and avoid unnecessary treatment andassociated adverse reactions occur, which will open up a new era ofindividualized treatment of chronic hepatitis B.
Keywords/Search Tags:metabonomics, HBV, immune active stage, biomarker
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