Résumé
Objective To analyze the mutation characteristics of immune escape-associated mutations in the main hydrophilic region (MHR) of HBsAg in patients with drug-resistant mutations in HBV RT. Methods The clinical data were analyzed from 6917 patients with C-genotype HBV infection attending to the hospital from July 2007 to August 2017. And these patients were treated with nucleoside/nucleotide analogs (NAs) and received drug resistance tests. The detection rate of drugresistant mutations in HBV RT was determined and the mutation characteristics of MHR immune escape-related mutations in HBsAg between drug-resistant mutations of HBV RT group and wild-type of HBV RT group were compared. Results Classical drug-resistant mutations in HBV RT occurred in 2585 chronic hepatitis B (CHB) patients treated with antiviral therapy, and the overall detection rate was 37.37% (2585/6917). The overall mutation rate of MHR in the drug-resistant mutations group of HBV RT was significantly higher than that in the wild-type group (30.00% vs. 17.13%, P<0.05). It was found that the detection rates of sQ101K/R/H, sS114T/A/L, sT/I126S/N/A, sG130N/R/K/A, sM133T/I, sS143T/L, sA159V/G, sE164D/G in HBV RT drug-resistant mutations group were higher than those in RT wild-type group (P<0.05). Conclusions Patients with HBV RT resistant mutations have a higher detection rate of MHR immune escape mutations in HBsAg, which suggested that MHR immune escape related mutations were closely related to HBV RT drug-resistant mutations.
Résumé
Objective: To compare the application of nucleotide drugs and the virology characteristics between patients with only N236T mutation and patients with N236T+A181T mutation in the HBV reverse transcriptase (rt) region. Methods: Sera of patients with only rtN236T mutation and patients with rtN236T+rtA181T mutation were obtained from patients with chronic hepatitis B. Then the levels of sero-HBsAg, HBV DNA and ALT were determined and the HBV genotypes were analyzed. The treatment history with nucleotide drugs was retrospectively reviewed. Results: The sero-HBsAg levels were not significantly different between only rtN236T mutation group and rtN236T+rtA181T mutation group (P = 0.9755), and significantly higher viral replication (P = 0.0014) and higher ALT level (P = 0.0032) were found in rtN236T+rtA181T mutation group. Moreover, compared to HBV B genotype, patients with HBV C genotype were prone to carry rtN236T+rtA181T mutation (40% vs 20.45%, P = 0.0235); also we noticed that a switch from lamivudine medication to adefovir medication was liable to induce the virus mutation. Conclusion: Nucleotide drug application in HBV patients with only rtN236T mutation and rtN236T+rtA181T mutation are concurrent (lamivudine switching to adefovir). However, the HBV genotype constituents and the serum virological characteristics are different between the two types of HBV patients.