Analysis Of Clinical And Virological Characteristics Of Chronic Hepatitis B Virus Infected Population With Concurrence Of HBeAg And Anti-HBe

?Objective? 1.To investigate the clinical features of concurrent HBe Ag and Anti-HBe in Population with chronic HBV infection.2.To explore the virological characteristic of concurrent HBe Ag and Anti-HBe in HBV core promoter,Pre C and C region.To clarify the mechanism of simultaneous HBe Ag and Anti-HBe.?Methods? 1.Clinical features of chronic HBV infected population with current HBe Ag and Anti-HBe.Collected data which belong to11,154 chronic hepatitis B virus Infected Population from the First Affiliated Hospital of Fujian Medical University.Gathered 302 infected people with current HBe Ag and Anti-HBe(HBe Ag+/Anti-HBe+)as GROUP ?,choose 905 infected people with HBe Ag positive and Anti-HBe negative(HBe Ag+/Anti-HBe-)as GROUP ? randomly,choose 1405 infected people with HBe Ag negative and AntiHBe positive(HBe Ag-/Anti-HBe+)as GROUP ? randomly.Collected their HBs Ag?HBe Ag?Anti-HBe?HBV DNA and other clinical data.Compare this data between three groups by using Oneway ANOVA test,F test,Kruskal-Wallis H test,Mann-Whitney U test,?2 test and Fisher exact test.2.Virological characteristic of concurrent HBe Ag and Anti-HBe.Collected serum from 60 people with current HBe Ag and Anti-HBe as experimental group,collected serum form 75 people randomly with HBe Ag+/Anti-HBe-as control group ?,collected serum form 104 people with HBe Ag-/Anti-HBe+ as control group ?.All of them were collected form the First Affiliated Hospital of Fujian Medical University who were chronic HBV infected.HBV DNA were Extracted and CP(core promoter),Pre C and C region was amplified by semi-nested PCR and sequenced.Mutations of CP,Pre C and C region were analyed.Use statistical tools to find the difference between three groups and charity the mechanism of HBe Ag+/Anti-HBe+ and clarified virological characteristics of current HBe Ag and Anti-HBe.?Results? 1.Clinical characteristics of chronic HBV infected population with current HBe Ag and Anti-HBe.Among the population with chronic HBV infection,the proportion of current HBe Ag+/Anti-HBe+ patients was 2.71%.The age distribution showed a trend of increasing first and then decreasing.It peaks at the age of 31 to 40(26.49%),with more males than females(70.00% vs.30.00%).The proportion of current HBe Ag and AntiHBe with HBs Ag ?250 IU/ml was between HBe Ag+/ Anti-HBe-and HBe Ag-/AntiHBe+ person.(88% VS 92% VS 55%,P < 0.001).HBe Ag titer [2.99(1.5-6.5)S/CO] was lower than that of HBe Ag+/ Anti-HBe-infected people [78.47(6.02-1287.82)S/CO](P < 0.001).The Anti-HBe titer [0.67(0.34-0.93)S/CO] of double positive patients was lower than that of HBe Ag-/Anti-HBe+ patients [0.01(0.01-0.02)S/CO](P < 0.001).HBV DNA > 500 IU/ml ratio: GROUP II > GROUP I > GROUP III(43% VS 29% VS 23%,P < 0.0001).The proportion of patients with liver cirrhosis from GROUP ?was higher than GROUP ?(14.2% VS 10.4%,P < 0.01).The proportion of patients with hepatic malignancy in the GROUP?was higher than GROUP ?(13.9% VS 3.9%,P < 0.01).The percentage of infected people whose ALT>80 U/L was much more in GROUP ? than GROUP ?(20% VS 8%,P < 0.0001).2.Virological characteristic of chronic HBV infected population with current HBe Ag and Anti-HBe.There have significant difference in genotype distribution among three groups(P < 0.0001),B/C genotype in the experimental group(50.59% VS 49.12%)and the control group ?(50.85% VS 49.15%)have average distribution,however,in control group?(82.81% VS 17.18%),genotype B account for more than genotype C.Nucleotide sequence analysis in the CP region showed that the experimental group had a higher mutation rate than the control group?(1.58% VS 1.12%,P < 0.05).In loci associated with disease progression,such as nt1753 and nt1762/1764,Experimental group is significantly higher than control group?(nt1753:20% VS 4%,nt1762/1764:47% VS 18%,P<0.05).What's more,experimental group shows a higher cumulative rate in disease progression associated loci than control group?and control group ?(0.24±0.2 VS 0.12±0.14 VS 0.17±0.17,P<0.05).As the Basic Core Promoter(Basic Core Promoter,BCP)area nucleotide mutations accumulated,HBe Ag showed a downward trend(r = 0.474,P < 0.05).For Pre C area we found that: only nt G1896 A mutation in control group ? was higher than experimental group(P < 0.05),the rest of the mutations had no statistical difference.C region sequence analysis showed that amino acid mutation loci of experimental group was mostly located in the antigenic peptides which were related to HLA-? or HLA-?.Amino acid mutation in C region of control group II was significantly higher than experimental group and control group I(5.42±3.82 VS 2.36±1.70 VS 1.91±1.87,P<0.0001).?Conclusions? 1.Current HBe Ag and Anti-HBe are associated with the progression of liver disease.2.There are many mutation sites related to disease progression in BCP region of current HBe Ag and Anti-HBe people who are chronic HBV infected.3.Cumulative nucleotide mutations in the BCP region is negatively correlated with HBe Ag,and higher cumulative mutations in the BCP region may be one of the reasons for the formation of HBe Ag+/ Anti-HBe+.7.The mutation in region C is higher in HBe Ag+/ Anti-HBe-chronic HBV infected people than HBe Ag+/ Anti-HBe+ people.