The Relevant Factors Affecting The Prognosis Of Hepatitis B Virus Infection

Background and Aims:Hepatitis B virus(HBV) is considered a major risk factor for the progression to liver cirrhosis and hepatocellular carcinoma(HCC).The serum level of HBV DNA is correlated with progression of the disease.The aim of the present study was to investigate the role of hepatitis B virus(HBV) replication in the development of hepatocellular carcinoma(HCC).Methods:170 cases of HCC and 276 control subjects free of HCC and cirrhosis were selected in this study.SerumHBV DNA levels was measured using fluorescein quantitative polymerase chain reaction assay(FQ-PCR at study entry and the last visit.Results:In a binary unconditional logistic regression analysis adjusted for age,cigarette smoking,alcohol consumption and family history of chronic liver diseases,the adjusted odds ratios(95%confidence interval) of HCC in patients with increasing HBV DNA level were 2.834(1.237-6.492), 48.403(14.392-162.789),42.252(14.784-120.750),and 14.819 (6.992-31.411) for HBV DNA levels≥10⁴-＜10⁵;≥10⁵-＜10⁶;≥10⁶-＜10⁷;≥10⁷copies/ml,respectively.Forty-six HCC cases were selected to compare the serums viral loads of HBV DNA at study entry with HBV DNA levels at the last visit.The HBV DNA levelsmeasuredat the two time points were of no statistically significant difference.Conclusions:The findings of this study provide strong longitudinal evidence of an increased hepatocellular carcinoma risk associated with the persistent elevation of serum HBV DNA level at 10⁴ to 10⁷ range. Background:Infection of hepatitis B virus(HBV) can lead to acute hepatitis,chronic hepatitis,and some will even progress to cirrhosis and hepatocellular carcinoma(HCC).Apart from the host' s immune response,the virus itself is also an important factor.Corelation between HBV mutation and pathogenesis has always been a hot topic in different countries and regions.However,the majority of the current study focused on horizontal comparison of HBV mutation among different liver diseases,lacking of longitudinal analysis ofgenemutationand different prognosis.Objective:To investigate HBV gene variations in the patients with primary liver cancer and compare HBV genome changes during the development of liver cancer.Meanwhile,HBV gene sequences in asymptomatic HBV carriers were analyzed.Methods:The subjects were from the Qidong,Jiangsu Province,a follow-up cohort of hepatitis B infectors.Primers were used to amplify HBV fragments from serum samples of 24 cases with HCC and 16 HBV asymptomatic carriers.After agarose gel electrophoresis,the samples were analyzed by double-sequencing to investigate mutations.Results:Among patients with HCC,no high frequency mutations were found in the PreS1,PreS2,S regions,nt1896 G-A mutation existed in 9/20 patients with HCC.nt1899 G-A mutation presented in 5/20 pations.One of them had 1896/1899 double mutations.17/18 patients with HCC showed nt1762 A-T/1764G-A mutation in Basal core promoter(BCP) region. Hepatitis B virus gene sequences did not change during HCC process.In asymptomatic group,15/16 successfully sequenced,of which 6 were found mutation in nt1896 G-A mutation.Three cases showed ntl899G-A mutation. No nt1896/1899 double mutations was found.9 / 16 were found nt1762 A-T/1764G-A mutation in BCP region.Conclusions:Mutation in PreC(nt1896) and basal core promotor(nt1762/1764) regions were common in HBV chronic infectors from Qidong,Jiangsu Province,one of the highest endemic area of hepatitis B and liver cancer.No meaningful changes of HBV gene sequences were found during HCC process. Background:Hepatocellular carcinoma(HCC) is one of the most common malignant tumors worldwide.Despite these scientific advances and the implementation of measures for early hepatocellular carcinoma detection in patients at risk,patient survival has not yet significantly improved during the last three decades.This is in part due to the advanced stage of the disease at the time of diagnosis.Current screening methodologies for liver cancer in at-risk patients rely on measuring the serum level of alpha-fetoprotein(AFP),a biomarker,as well as ultrasound imaging. AFP's sensitivity is very limited since many other liver diseases can result in a very high blood level of AFP similar to that observed in HCC. In addition,AFP is not always elevated in the early stages of cancer development,when therapy is mostly effective.Imaging,on the other hand, depends to a large extent on the operator.Therefore,better diagnostic methods are needed to increase the survival rate in liver cancer patients. We developed a bead-based affinity-fractionated proteomic method to discover novel serum biomarkers for HCC.Methods:Affinity purification of serum with magnetic beads and matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry(MALDI-TOF MS) analysis were used to screen potential liver cancer markers.We compiled MS protein profiles for 24 HCC patients with HBV infection,and compared them with profiles from 24 healthy controls and 25 patients with chronic hepatitis B..The spectra were analyzed statistically using flexAnalysis^TM and ClinProt^TM bioinformatic software. In each MS analysis,the peak intensities of interest were normalized with an internal standard.Results:To optimize MALDI-TOF analysis based on the best discriminator of the cancer and control spectra,copper-chelated beads were used for plasma protein profiling.Five markers that differentiated between cancer and chronic hepatitis B spectra were found,with molecular masses of 1405,1906,1256,1421,2694 Da.Eight distinguished markers differentiated between cancer and healthy controls spectra were detected, with molecular masses of 4779,1406,4197,5333,5478,5520,4078,4107 Da.Conclusions:MALDI-TOF MS offers a unique platform for detecting markers for hepatocellular carcinoma.It also offers a noninvasive method to further study the proteomic changes in the development and progression of liver cancer.