Study On The Relationship Between Different Pre-S Deletions Mutations And Hepatitis B Virus Genotypes And Their Clinical Progress

Objective: To investigate the relationship between different types of pre-S deletion mutations and hepatitis B virus genotypes and their clinical progression.Methods: A total of 359 HBV carriers were enrolled,ie 22 asymptomatic carriers,133 chronic hepatitis B,124 cirrhosis(LC),and 80 liver cancer(HCC).The nucleotide sequence of 359 HBV carriers was previously determined by Taqman probe method,and the pre-S region,basal core promoter(BCP)mutation and pre-C region(PC)mutation were detected.A total of 77(21.4%)carriers carried pre-S deletions;comparisons between pre-S deletion mutations were performed on carriers of genotype B(HBV/B)infection and carriers of genotype C(HBV/C)infection.Results: The proportion of BCP mutations in the non-pre-S-region carriers in HBV carriers was lower than that in the pre-S-deletion carriers(P=0.020).The proportion of LC in the HBV carriers missing in the pre-S region was lower than that in the non-pre-S region(p=0.045).In the pre-S region,HBV/B and HBV/C were absent;the proportion of HBV/B type BCP mutations was significantly lower than that of HBV/C type(p<0.001);HBV/B type had a significant proportion of PC mutations.The proportion of carriers above HBV/C type(p=0.007);the proportion of HBV/C carriers who developed liver cancer was higher than that of HBV/B carriers(P=0.048).The C-terminal deletion ratio of HBV/B pre-S1 in the two genotypes was significantly higher than that in HBV/C type(p=0.004);the frequency of simultaneous deletion of HBV/B carriers in PreS1 and PreS2 regions was higher than HBV/C.Type carrier(p=0.012).Epitope mapping showed that HBV/B type gene deletion ratio in PS1-T1 region was significantly higher than HBV/C type(p=0.015);HBV/B type PS2-B1 in pre-S2 region was higher than HBV/C type(p=0.001).The functional map showed that the proportion of gene deletion in the S promoter region and HSC70 region of HBV/B type was higher than that of HBV/C type(S promoter: p=0.005;HSP70: p=0.021);VS region of HBV/B type The rate of deletion was significantly higher than that of HBV/C(p=0.001).The difference in pre-S deletion mutation ratio between HBV/B genotype liver cancer patients and HBV/C genotype liver cancer patients in liver cancer patients(p=0.083).The difference in the rate of deletion of HBV/B and HBV/C in the PreS2 region in patients with liver cancer missing from the pre-S region(P=0.162).Conclusions: HBV/B and HBV/C carriers showed different frequencies of pre-S deletion mutations and were associated with the progression of liver diseases.