AUTHOR=Castro Gonzalo M. , Sosa María J. , Sicilia Paola E. , Riberi María I. , Moreno Claudia , Cattaneo Rodolfo , Debes José D. , Barbás María G. , Cudolá Analía E. , Pisano María B. , Ré Viviana E. 

TITLE=Acute and chronic HBV infection in central Argentina: High frequency of sub-genotype F1b, low detection of clinically relevant mutations and first evidence of HDV

JOURNAL=Frontiers in Medicine

VOLUME=Volume 9 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2022.1057194

DOI=10.3389/fmed.2022.1057194

ISSN=2296-858X

ABSTRACT=Genomic analysis of hepatitis B virus (HBV) identifies phylogenetic variants, which may lead to distinct biological and clinical behaviors. The satellite hepatitis D virus (HDV) may also influence the clinical outcome in patients with hepatitis B. 
The aim of this study was to investigate HBV genetic variants, including clinically relevant mutations, and HDV infection in acute and chronic hepatitis B patients in central Argentina. 
A total of 217 adult HBV infected patients [acute (AHB): n=79; chronic (CHB): n=138] were studied; 67 were HBV/HIV coinfected. Clinical and demographic data were obtained from medical records. Serological markers were determined. Molecular detection of HBV and HDV was carried out by RT-Nested PCR, followed by sequencing and phylogenetic analysis.
Overall, genotype (gt) F [sub-genotype (sgt) F1b] was the most frequently found. In AHB patients, the gts/sgts found were: F1b (74.7%) > A2 (13.9%) > F4 (7.6%) > C (2.5%) > A1 (1.3 %). Among CHB patients: F1b (39.1%) > A2 (23.9%) > F4 (18.2%) > D (9.4%) > C and F6 (3 .6% each) > A1, A3 and B2 (0.7% each). The distribution of sgt A2 and gt D was significantly different between HBV mono and HBV/HIV coinfected patients [A2: 15.9% vs 35.7% (p<0.05) and D: 14.6% vs 1.8% (p<0.05)]. Mutation frequency in BCP/pC region was 35.5% (77/217) [AHB: 20.3% (16/79), CHB: 44.2% (61/138)]. In ORF-S, mutations associated to vaccine escape and diagnostic failure were detected in 7.8% of the sequences (17/217) [AHB: 3.8% (3/79), CHB: 10.1% (14/138)]. ORF-P amino acid substitutions associated to antiviral resistance were detected in 3.2% of the samples (7/217) [AHB: 1.3% (1/79), CHB 4.3%, (6/138)]. The anti-HDV seropositivity was 5.2% (4/77); one sample could be sequenced, belonging to gt HDV-1 associated to sgt HBV-D3.
We detected an increase in the circulation of genotype F in Central Argentina, particularly among AHB patients, suggesting transmission advantages over the other genotypes. A low rate of mutations was detected, especially those with antiviral resistance implications, which is an encouraging result. The evidence of HDV circulation in our region, detected for the first time, alerts the health system for its search and diagnosis.