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

Introduction: 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 clinical outcomes in patients with hepatitis B. The aim of this study was to investigate...

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Detalles Bibliográficos
Autores: Castro, Gonzalo Manuel, Sosa, María J., Sicilia Don, Paola Ermelinda, Riberi, María I., Moreno, Claudia, Cattaneo, Rodolfo, Debes, José D., Barbás, María G., Cudolá, Analía E., Pisano, María Belén, Ré, Viviana Elizabeth
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/222513
Acceso en línea:http://hdl.handle.net/11336/222513
Access Level:acceso abierto
Palabra clave:ANTIVIRAL RESISTANCE
ARGENTINA
GENOTYPES
HBV
HEPATITIS B VIRUS
MUTANT
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario:Introduction: 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 clinical outcomes 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. Methods: A total of 217 adult HBV infected patients [acute (AHB): n = 79; chronic (CHB): n = 138] were studied; 67 were HBV/human immunodeficiency virus (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. Results: 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), respectively and D: 14.6% vs. 1.8% (p < 0.05), respectively]. Mutation frequency in basal core promoter/pre-Core (BCP/pC) region was 35.5% (77/217) [AHB: 20.3% (16/79), CHB: 44.2% (61/138)]. In the open reading frame (ORF) S, mutations associated with 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 with 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 with sgt HBV-D3. Discussion: 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, reported for the first time, alerts the health system for its search and diagnosis.