Increased intrahepatic quasispecies heterogeneity correlates with off-treatment sustained response to nucleos(t)ide analogues in e antigen-positive chronic hepatitis B patients

摘要: Finite treatment with nucleos(t)ide analogues (NAs) remains a great challenge for chronic hepatitis B in the clinic. This study aimed to investigate relationship between intrahepatic quasispecies heterogeneity and NAs off-treatment outcomes prospective cohort. Eighteen HBeAg-positive patients who achieved cessation criteria underwent liver biopsy, stopped thereafter. Patients were followed up prospectively 1 year. The reverse transcriptase (RT) gene of virus (HBV) was cloned sequenced. Intrahepatic specific mutations analysed using bioinformatic methods. Ten sustained response, eight developed viral relapse. Shannon entropy nucleotide diversity within either RT or surface (S) region response significantly higher (p < 0.05) than those had at level predicted (area under receiver operating characteristics curve 0.925; 95% CI 0.807-1.000; p 0.003). More positive selection sites N-glycosylation S found relapse 0.01). Most located reported HLA-I-restricted HLA-II-restricted epitopes. end correlated B. immune escape response. indicated more robust control over HBV, which turn maintained after withdrawal NAs.