Analysis Of The Relationship Between Hepatitis B Virus Precore And Basal Core Promoter Mutations And Acute-on-chronic Liver Failure

Objective:To analyze the relationship between Hepatitis B virus precore(PC) and basal core promoter(BCP) mutations and HBV-related acute-on-chronic hepatitis B liver failure (HBV-ACLF).METHODS:44patients with ACLF and28patients with chronic hepatitis B(CHB) were enrolled in this study, and10ACLF patients were monitored, and sera were collected once every one week after treatment.HBV DNA, ALT, TBil, albumin in the serum were examined. The PC and BCP gene fragments were amplified by nested PCR.HBV genotype and BCP/PC mutations were determined by direct sequencing and analyzed by BioEdit(7.0.9.0). HBV DNA in serum was measured by a real-time PCR assay. Clinical data, Fisher’s exact probability, Chi-Square Test, T test were calculated by SPSS13.0to study the relationship between Hepatitis B virus PC and BCP mutations and ACLFRESULTS:Cilinical data:Between ACLF cohort and CHB cohort, there were significant difference with comparison of Age(51.64±10.89) vs (38.65±10.52) years(P=0.000), ALB(26.41±3.47) vs (42.45±5.67)(g/L)(P=0.000), TBIL(2.21±0.40) vs (1.09±0.66)log10(μmol/L)(P=0.000),and HBV DNA(5.47±1.20)vs(7.42±1.29)log10(copies/ml)(P=0.000), whereas there were no significant difference in gender, ALT level and genotype.Squence analysis:1.A11of44ACLF patients were genotype C. In CHB cohort, genotype B was only found in2cases, and others were genotype C.2.Single mutation including A1762T, G1764A, T1753V,G1896A and G1899A and combined mutations A1762T+G1764A, G1896A+G1899A, T1753V+A1762T+G1764A,G1896A+G1899A+A1762T+G1764A and A1762T+G1764A+G1896A were more frequently detected in patients with ACLF than in patients with CHB (P<0.05).3.A significantly higher ratio of PC/BCP wild-type sequences was found in patients with CHB than in patients with ACLF(17.86%vs2.27%)(x2= 5.440,P=0.020). The ratio of both PC and BCP mutations in ACLF was significantly higher than CHB (79.55%vs39.29%)(x2=12.021,P=0.001). The ratio of only BCP mutation occurrence was42.86%in CHB patients in contrast to20.45%in ACLF patients (x2=4.157,P=0.041). Only PC mutation occurrence was not found both in CHB and ACLF cohort.4.In different MELD scores with ACLF, there were no statistically significant difference both in single mutation and combined mutations.5. Of10ACLF patients, we monitor their HBV PC and BCP mutation status. Analysis showed that the combined mutations were found all of the10patients, and G1896A、G1899A、T1753、A1846T mutations occurred at the early stage of ACLF, with clinical status improved, the muataions disappeared,but the combined mutations were still exist.CONCLUSIONS:The Hepatitis B virus PC and BCP mutation occurrence were significantly higher in ACLF patients than in CHB patients, and there was statistically significant difference. Moreover, the combined mutations and PC mutation were more common in ACLF. In different MELD scores with ACLF, there were no statistically significant difference both in single (?)(?)(?) and combined mutations.G1896A、G1899A、 T1753C、A1846T mutations were associated with ACLF.