Relationship Of Hepatitis B Virus Mutations And HBV-related Acute-on-chronic Liver Failure

AIM:To investigate the relationship between Hepatitis B Virus(HBV) mutations and HBV-related acute-on-chronic liver failure(ACLF).METHODS:Serum were collected from 20 HBV-related ACLF and 19 chronic hepatitis B(CHB) patients.A sensitive and reliable nested PCR assay was performed to analyze the target HBV gene fragments,which were further sequenced and analyzed by BioEdit(7.0.9.0).Fisher's exact probability or t test were calculated by SPSS 17.0 to analyze the relationship between HBV mutations and HBV-related ACLF.RESULTS:Cilinical data:Between ACLF and CHB group,there were significant difference of age(49.70±14.33 vs 40.37±10.91years, P<0.05),ALB (27.31±3.39 vs 43.16±4.35g/L,P<0.05),TBIL(287.37±133.02 vs 19.75±19.99μmol/L, P< 0.05), HBeAg(+) (40.00% vs 73.68%, P<0.05),and HBV DNA (5.82±1.52 vs 7.67±0.85copies/ml,log10, P<0.05),whereas there was no significant difference in gender and ALT. No difference of HBV DNA and clinical improvement rate was found between HBeAg(+) and HBeAg(-) ACLF patients [6.21±1.51vs5.70±1.60 (copies/ml,log10),62.50% vs 66.67%, P> 0.05].Squence analysis:1. Genotype: 16 of 20 ACLF cases were sequenced successfully,all of 16 ACLF patients were genotype C.In CHB group,17 of 19 cases were sequenced completely,genotype B was only found in 2 cases,and other 15 were genotype C.2. We detected PreS1 and PreS2 deletion, PreS2 were found in 8 cases,7 patients(35.00%) were in the ACLF group and 1 patient(5.26%) was in the CHB group.There were significant correlations between PreS2 deletion and HBV-related acute-on-chronic liver failure (P<0.05).3. G1896A,G1899A and G1896A+G1899A mutations occurrence were significantly high in ACLF patients than in CHB patients (56.25% vs 12.50%, 37.50% vs 6.25%,31.25% vs 0.00%,P<0.05).Although A1762T,G1764A, A1762T+G1764A mutations were observed in two groups (81.25% vs 75.00%, 87.50% vs 75.00%,81.25% vs 75.00%),no difference was found between two groups(P>0.05).4. No G587A mutation was found in two groups,4 of 16 patients presented C766G mutation (25.00% vs 0.00%,P<0.05)and only 1 patient presented YMDD mutation.5. A patient with ACLF was monitored more than 2 months,HBV mutations analysis showed that PreS2 deletion,G1896A+G1899A+A1762T+ G1764A,C766G and T1961C mutations occurred at early stage of ACLF,PreS2 deletion,G1896A+G1899A and T1961C muataions disappeared with clinical condition improved,but A1762T+G1764A and C766G mutations still existed.CONCLUSIONS:PreS2 deletion,G1896A,G1899A and G1896A+G1899A mutations were associated with HBV-related ACLF.Although A1762T,G1764A and A1762T+G1764A mutations often existed in both HBV-related ACLF and CHB patients,there was no relationship bewteen A1762T,G1764A,A1762T+G1764A mutations and HBV-related ACLF.