|
Basic Characteristics of Mutations
|
|
Mutation Site
|
A1762T |
|
Mutation Site Sentence
|
Baseline HN (p < 0.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (p = 0.03), HBeAg titre (p = 0.0002), or the presence of HBV basal core promoter (A1762T, p = 0.0379 and G1764A, p = 0.0176) or G1896A precore mutations (p = 0.0218). |
|
Mutation Level
|
Nucleotide level |
|
Mutation Type
|
Nonsynonymous substitution |
|
Gene/Protein/Region
|
BCP |
|
Standardized Encoding Gene
|
|
|
Genotype/Subtype
|
D;A |
|
Viral Reference
|
-
|
|
Functional Impact and Mechanisms
|
|
Disease
|
Hepatitis B, Chronic
|
|
Immune
|
- |
|
Target Gene
|
-
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
- |
|
Location
|
- |
|
Literature Information
|
|
PMID
|
36427857
|
|
Title
|
Hepatitis B virus haplotype number at baseline is a predictive marker of functional cure during antiviral therapy for patients with genotypes A and D HBeAg-positive chronic hepatitis B
|
|
Author
|
Wagner J,Yuen L,Littlejohn M,Sozzi V,Jackson K,Martin R,Aeschbacher T,Suri V,Tan SK,Feierbach B,Gaggar A,Marcellin P,Buti Ferret M,Janssen HLA,Gane E,Meagher N,Price DJ,Wong D,Thompson AT,Revill PA
|
|
Journal
|
Alimentary pharmacology & therapeutics
|
|
Journal Info
|
2023 Mar;57(5):509-523
|
|
Abstract
|
BACKGROUNDS AND AIMS: We investigated associations between hepatitis B virus (HBV) genome-length haplotype number (HN) at baseline in subjects with HBeAg-positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct-acting antiviral therapy METHOD: We analysed 86 HBeAg-positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg-positive CHB. RESULTS: In the HBeAg-positive test cohort, patients with genotypes A or D and =2 haplotypes had a minimum of 21-fold higher likelihood of achieving HBsAg loss on TDF. Baseline HN (p < 0.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (p = 0.03), HBeAg titre (p = 0.0002), or the presence of HBV basal core promoter (A1762T, p = 0.0379 and G1764A, p = 0.0176) or G1896A precore mutations (p = 0.0218). This finding was validated in the independent validation cohort. HN was statistically higher in patients with HBV genotypes B or C infection compared to genotypes A and D. CONCLUSION: Baseline HN =2 predicts which patients with HBV genotypes A or D will more likely progress to functional cure on current direct-acting antiviral therapy, with greater accuracy than current biomarkers including baseline HBsAg and HBeAg titre.
|
|
Sequence Data
|
-
|
|
|