HBV Genotype Distribution In Jilin And Its Correlation With Adefovir Dipivoxil Treatment

Hepatitis B virus (HBV) was one of the most common virus that affectednearly 400 million people worldwide and resulted in chronic hepatitis. Amongthem, 75% occurred in Asia. Infection with this virus was the major reason thatleaded to chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently,the relationship between HBV heterogeneity and anti-virus drugs became thestudy hotspot, because there was some correlation between virus variation anddisease.Hepatitis B virus (HBV) has been classified into 8 genotypes based oncomplete nucleotide sequence divergence. Genotypes of HBV had distinctgeographical distributions. Recently, it was found that there were correlationbetween HBV genotypes and HBV transmission, clinical disease prognosis andthe choice of anti-virus drugs. Currently there were some diagnostic methods ofgenotype, including the complete genome sequence analysis or S gene sequencing,polymerase chain reaction(PCR), PCR-RFLP, micro-board nucleic acidhybridization ELISA, monoclonal antibody EIA, type-special primer PCRgenotyping, probe hybridization,etc. INNO-LiPA HBV Genotyping method(INNOGENETICS Company, Belgium) had a high susceptive for genotyping(especially for the mixed genotype). It was convenient for quality-contral andstandardized operation.Objective: To study HBV genotype distribution of chronic hepatitis Bpatients (HBeAg positive) in Jilin province and its correlation with AdefovirDipivoxil short-term treatment.Methods: HBV genotypes were detected by INNO-LiPA HBV Genotypingmethod after HBV gene segments were amplified by nest-PCR. Serum HBV DNAwas tested by Roche COBAS AMPLICOR HBV MONITOR (the low limitation is200 copies/ml). HBV genotyping were done in 73 chronic hepatitis B patients (HBeAgPositive) were in Jilin province. All cases came from the Infectious DiseaseDepartment of the First Hospital of Jilin University from 2001 to 2004. Amongthese cases, male vs famale: 61/12; Aged from 14 to 51 years; Average age(years):31.4±9.7; All cases: HBsAg positive, HBeAg positive, anti-HBc positive. Courseof disease(years): 6.37±4.62 ; ALT (U/L) 123.9±104.2 ; HBV DNA 8.38±0.92 lg. 40 cases accepted Adefovir Dipivoxil short-term treatment. Aged from 19 to51 years; average age (years): 33.6±8.7; male vs famale: 29/11; diseasecourse(year):5.74±5.23;ALT169.0±107.9ULN ;HBV DNA 8.32±0.95lg. BothHBsAg and HBeAg had been positive for 6 monthes or more in serum. SerumHBV DNA ≧106 copies/ml, ALT > normal value, excluding hepatocellularcarcinomar, discompensive liver cirrhosis, AIH; anti-HCV negative, anti-HIVnegative, anti-HDV negative; without lamivudine and other anti-virus drugstreatment within recent three months. Trial was divided into four phases. Phase 1: Random, double blind, takingplacebo orally qd,, totally 12 weeks. Patients accepted Adefovir Dipivoxil andplacebo in the proportion of 3 vs 1. Phase 2: All cases accepted AdefovirDipivoxil treatment openly. Phase 3: The patients who accepted AdefovirDipivoxil treatment in phase 1 had been devided into Adefovir Dipivoxil groupand placebo group in the proportion of 2 vs 1 randomly for 12 weeks. Whereas thepatients who took placebo in phase1 would take Adefovir Dipivoxil continuely.Phase 4: All the patients still in trial would accepted Adefovir Dipivoxil treatment.40 cases were included in trial groups. Among them, one case retreated fromthe trial for her procreating after 28 weeks. So, 39 cases had been completed intotal 40 weeks trial. 29 cases had been completed in total 92 weeks trial.Otherwise, one case retreated from the trial for multiple metastasis of stomachcarcinoma after 80 weeks. Now 38 cases had been treated for 108 weeks. Firstly, we compared Adefovir Dipivoxil group(12 weeks) and placebogroup(12 weeks) in therapeutic effect. Secondly, Adefovir Dipivoxil group(0 week)and Adefovir Dipivoxil group(40 weeks) were compared in 39 cases. The data ofAdefovir Dipivoxil groups (0 week, 40 weeks and 92 weeks) in 29 cases wascompared, respectively. We also compared thirty-one single genotypes patients with eight mixedgenotypes patients, HBV DNA logarithm value and ALT in two teams. Result: There were seven B genotypes, fifty-two C genotypes, ten B+Cgenotypes, four B+C+D genotypes in seventy-three cases. Infection rate of Cgenotype was highest than others. There were two B genotypes, thirty Cgenotypes, five B+C genotypes, and three B + C+ D genotypes in AdefovirDipivoxil group (forty cases). Among them, infection rate of C genotype washighest than others. Adefovir Dipivoxil group (12 weeks) and placebo group (12 ·8·weeks) were compared in therapeutic effect. Its results as follow: AdefovirDipivoxil group---Serum HBV DNA decreased 3.45 logarithm to baseline.Recovery rate of ALT was 50% (15/30). Control group---Serum HBV DNAincreased 0.41 logarithm to baseline. The results of 20 patients treated withAdefovir dipivoxil for 0, 40 and 92 weeks show that serum HBV DNA decreased4.46Lg, 4.5Lg, recovery rate of ALT is 77.8%, 85.2% ;AST 91.7%, 95.8%. Thedecrease value of ALT and HBV DNA log in single genotypes and mixedgenotypes patients has no significance. We think that there is no relation betweenmixed genotype and Adefovir dipivoxil therapy effect. When the therapeuticcourse is 108 weeks, HBeAg of 17 cases converse, HBeAb of 11 cases converse.There are 16 C genotype cases and 1 B+C+D genotype case. HBV DNAlogarithm value and ALT in thirty-two single genotypes patients with eight mixedgenotypes patients have no statistic significance before treated with Adefovirdipivoxil and treated for 40 weeks. Discussion: We detected HBV genotypes of 73 HBeAg positive CHB casesin Jilin province. The results showed that HBV genotype of HBeAg positive CHBcases in Jilin province included B, C, B+C and B+C+D genotypes. Thepercentage of C genotype is the highest, which indicates the infection of Cgenotype has relation with the development of CHB. These results arecoincidence with studies in China. But the percentage is higher in our study,which is relative with the development of CHB. All cases are HBeAg positive andreoccurrence. We compared HBV DNA and ALT recovery rate of patients treated withAdefovir dipivoxil and placebo for 12 weeks, respectively; 39 cases treatedcontinually with Adefovir dipivoxil for 0 and 40 weeks; we compared the data of29 cases in 0 and 40 weeks that were treated continually with Adefovir dipivoxilfor 92 weeks. The results of the Adefovir dipivoxil group and placebo groupshowed that the serum HBV DNA decreased 3.45lg compared with baseline,recovery rate of ALT is 50%(15/30); serum HBV DNA in control group increased0.41lg compared with baseline, recovery rate of ALT is 10% (1/10). There issignificant difference between two groups, which is coincidence with the studiesin other countries. Otherwise, ALT recovery to normal level in 8/39 cases treated for 40 weeks,there are 5 fatty liver cases in these cases. The results indicated that the effect ofAdefovir dipivoxil is not very good to patients combining fatty liver. The resultsof 29 cases in 0 and 40 weeks that were treated continually with Adefovirdipivoxil for 92 weeks showed that the HBV DNA decreased 4.46lg and 4.65compared with baseline, the recovery rate of ALT is 77.8%, 85.2%; AST is 1.7%and 95.8. The effect of Adefovir dipivoxil increases with the elongation oftherapeutic course, which indicate that the CHB patients should be treated withAdefovir dipivoxil for a long time. 3/29 cases combining with fatty liver did notrecovery to normal level, which indicate that combining fatty liver have influenceon the effect of Adefovir dipivoxil, but the reason is not clear. The decrease of ALT and HBV DNA log value in single genotype and mixedgenotype cases has no significance. When the total therapy course is 108 weeks,HBeAg of 9 cases converse, HBeAb of 11 cases converse. There is a C genotypecase and a B+C+D genotype case. Auording to our data. we think gentypes inchronic activition hepatitis B is patients (HBeAg positive) had no obviousdifference with therapy effect of Adefovir dipiwxil. INNO-LiPA HBV gene Kit of INNOGENETICS Company had a high...