The aim of this study was to assess the frequencies and patterns of naturally occurring genotypic resistance to nucleos(t)ide analogues (NUCs) and typical hepatitis B surface antigen (HBsAg) amino acid substitutions in naive hemodialysis (HD) patients with chronic hepatitis B. In order to achieve this, the genotypic resistance to NUCs and HBsAg amino acid substitutions were classified into primary/compensatory resistance mutation and antiviral drug-associated potential vaccine-escape mutation (ADAPVEM)/typical HBsAg amino acid substitution, respectively. Direct sequencing of polymerase (pol) gene of hepatitis B virus (HBV) was performed on DNA samples obtained from 248 HBsAg-positive Turkish patients. Overall, 38% (n = 94) of HBsAg-positive HD patients had detectable HBV DNA in their serum. Naturally occurring primary and compensatory resistance mutations to NUCs were detected in 30% (n = 28) and 52% (n = 49) of HD patients, respectively. However, 6 types of ADAPVEMs and 48 types of typical HBsAg amino acid substitutions were found in 10.6% (n = 10) and 46% (n = 43) of the HD patients, respectively. Our study suggests that every HD patient diagnosed with chronic hepatitis B, who is a potential candidate for NUCs treatment, should also be monitored for the baseline pol gene sequence changes before the initial treatment, for a more effective management of future treatment options. Further, a relatively higher frequency of ADAPVEMs variants needs to be addressed as a public health problem.
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http://dx.doi.org/10.7883/yoken.65.495 | DOI Listing |
Clin Exp Med
January 2025
Guangzhou Huayin Health Medical Group Co., Ltd, Guangzhou, 510515, China.
Coexistence of hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) has been observed in some chronic hepatitis B (CHB) patients (DP patients), but the clinical outcomes and comprehensive characterization of immune micro-environmental changes for this specific population remain inconclusive. In this study, we retrospectively analyze the prognosis of 305 patients in Foshan City, Guangdong Province, China, and also investigated the molecular immunology changes in HBsAg and anti-HBs double positive CHB patients (DP group), CHB patients who had recovered from IFN-ɑ treatment (RP group), and healthy controls (HC group) using T cell receptor (TCR) and B cell receptor (BCR) immune repertoire sequencing. Our findings revealed that 22.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Microbiology, Faculty of Science, Kasetsart University, Bangkok, Thailand.
The "a" determinant, a highly conformational region within the hepatitis B virus large surface protein (LHBs), is crucial for antibody neutralization and diagnostic assays. Mutations in this area can lead to conformational changes, resulting in vaccination failure, diagnostic evasion, and disease progression. The "a" determinant of LHBs contains a conserved N-linked glycosylation site at N320, but the mechanisms of glycosylation in LHBs remain unclear.
View Article and Find Full Text PDFBioorg Chem
December 2024
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Guangzhou 510515, China. Electronic address:
The inhibition of HBV DNA and elimination of HBsAg has already been established as an indicator for HBV clinic cure, and a novel dual-targeting inhibitors of HBV polymerase/entry are designed and synthesized in this study. Pentacyclic triterpenes (PTs) scaffold of exhibiting a high affinity to NTCP, including glycyrrhitinic acid (GA), oleanolic acid (OA), ursolic acid (UA), and betulinic acid (BA) were linked neatly with the nucleoside drug zidovudine (AZT) through a molecular hybrid strategy to synthesize twenty of PTs-AZT conjugates for targeting HBV polymerase as well as sodium taurocholate cotransporting polypeptide (NTCP). The conjugates showed significant inhibitory effects on the secretion of HBsAg and HBeAg in HepG2.
View Article and Find Full Text PDFNat Commun
November 2024
Immunocore Ltd, 92 Park Drive, Abingdon, Oxfordshire, OX14 4RY, UK.
The non-polymorphic HLA-E molecule offers opportunities for new universal immunotherapeutic approaches to chronic infectious diseases. Chronic Hepatitis B virus (HBV) infection is driven in part by T cell dysfunction due to elevated levels of the HBV envelope (Env) protein hepatitis B surface antigen (HBsAg). Here we report the characterization of three genotypic variants of an HLA-E-binding HBsAg peptide, Env identified through bioinformatic predictions and verified by biochemical and cellular assays.
View Article and Find Full Text PDFWorld J Hepatol
October 2024
Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China.
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