Clinical Study On The Relevance Between HBV PreS Mutations And Advanced Liver Disease

Master Candidate:Yao PeijunSupervisor:Associate professor Gao Jianpeng[Aim] To investigate the prevalence of PreS mutations and to assess their association with HBV-related advanced liver disease progression in three tertiary hospital of Kunming in Yunnan Province.[Methods] Blood samples and clinical data of patients with hepatopathy were investigated. Seventy-one subjects were included:21chronic hepatitis B (CHB)(including5acute-on-chronic liver failure, ACLF),41liver cirrhosis (LC)(including5ACLF) and9hepatocellular carcinoma (HCC). DNA of Hepatitis B Virus (HBV) from all samples were extracted. HBV genotyping was performed with a detection kit. PCR assay was performed to analyze the target HBV gene fragment,the Pre-S region of all HBV DNA was amplified and sequenced. Pre-S mutations were analyzed by Chromas and DNAstar software, as well as SPSS software for statistics. Possible correlations between Pre-S mutations and HBV-related advanced liver disease progress were examined.[Results]1Squence analysis1.1Among71cases,the distribution of HBV genotype was as follows:genotype C alone in49,genotype B alone in21,mixed genotype B and C in1.Genotype C and B in group CHB, group LC and group HCC, were14vs7-.28vsl2>7vs2, respectively.There was no significant difference among the three groups in the distribution of genotype C (P>0.05).HBV PreS mutations were detected in33of71cases(46.48%).As for the prevalence of PreS mutations according to site,PreS2mutation was the most commonly found mutation(19),followed by preSl-S2mutation(12) and PreSl mutation(2). The highest prevalence of the PreS mutations was found in HCC(66.67%),followed by LC(48.78%) and CHB(not include ACLF)(18.75%).There was a significant difference in prevalence of these mutations between CHB and LC or HCC(P<0.05),but the prevalence of PreS mutations of LC was similar to that of patients with HCC(P>0.05).In addition,ACLF (80%) had a higher frequency of PreS mutations than CHB (P<.005).There were significant correlations between PreS mutations and HBV-related ACLF.1.2The proportion of viral load(?)104copies/ml in the patients with PreS mutations(30,99.9%) was significantly higher than those without mutation(19,50.0%)(P<0.001).There were significant correlations between PreS mutations and HBV at high replicative phase.But there were no significant differences between the patients with and without PreS mutations in sex,in terms of age distribution,in the distribution of genotype C(P>0.05).2Patient Clinical Data2.1No significant differences were observed in sex,in terms of age distribution,HBeAg status,or in HBV DNA levels((?)104copies/ml),among the three groups of CHB(not include ACLF), LC and HCC.2.2There were no significant differences between the group HBV-related ACLF and group CHB in sex,in terms of age distribution,HBeAg status,or in HBV DNA levels((?)104copies/ml).2.3To compare the liver function(ALT, ALB and TBIL)among the group CHB、LC and HCC.Serum ALB levels was significantly higher in patients with CHB (P<0.001), but there was no significant difference between the LC and the HCC group. The highest serum TBIL levels was found in group HCC,followed by LC and CHB.The serum TBIL levels of each group increased as disease severity increased (P<0.05).There was no significance comparing ALT among three groups because of its unstable degree of variation.2.4Among71cases,the proportion of all patients with history of antiviral treatment was43.66%(31/71), respectively in group CHB(not include ACLF),LC and HCC were62.5%、41.46%、22.22%, there was no significant difference in the proportion of antiviral treatment among three groups (P>0.05).And there was no significant difference between the ACLF(40%) and the CHB group in the proportion of antiviral treatment (P>0.05)[Conclusion]1HB V genotype from three tertiary hospital of Kunming mostly belonged to C and B, genotype C was the predominant genotype.2Among all the detection rates of Pre-S mutation,PreS2mutation was the most commonly found mutation,followed by preS1-S2mutation and PreS1mutation.3PreS mutations would lead HBV replication to a higher level.HBV-related advanced liver disease was significantly more common in patients with PreS mutation.As the illness worsen, detection rate of Pre-S mutation increased, and it would be easier to cause the HBV-related advanced liver disease as well as ACLF.