Original Article
Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Sep 21, 2013; 19(35): 5813-5827
Published online Sep 21, 2013. doi: 10.3748/wjg.v19.i35.5813
Molecular epidemiology and putative origin of hepatitis C virus in random volunteers from Argentina
Noemí del Pino, José Raúl Oubiña, Francisco Rodríguez-Frías, Juan Ignacio Esteban, María Buti, Teresa Otero, Josep Gregori, Damir García-Cehic, Silvia Camos, María Cubero, Rosario Casillas, Jaume Guàrdia, Rafael Esteban, Josep Quer
Noemí del Pino, Apunlab Laboratories, Buenos Aires C1428CRB, Argentina
José Raúl Oubiña, Institute of Medical Microbiology and Parasitology (IMPAM) UBA-CONICET, Department of Microbiology, Parasitology and Immunology, Faculty of Medicine, University of Buenos Aires, Buenos Aires C1121ABG, Argentina
Francisco Rodríguez-Frías, Silvia Camos, CIBER de Enfermedades Hepáticas y Digestivas (CIBERehd) del Instituto de Salud Carlos III, and Biochemistry Department, Hospital Universitari Vall d’Hebrón (HUVH), 08035 Barcelona, Spain
Juan Ignacio Esteban, María Buti, Jaume Guàrdia, Rafael Esteban, Josep Quer, CIBERehd del Instituto de Salud Carlos III, Autonomous University of Barcelona and Liver Unit, Internal Medicine, Lab. Malalties Hepatiques, Vall d’Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d’Hebrón (HUVH), 08035 Barcelona, Spain
Teresa Otero, Unitat de Diagnostic Molecular, HUVH, 08035 Barcelona, Spain
Josep Gregori, Liver Unit Internal Medicine, Lab Malalties Hepatiques, VHIR-HUVH, 08035 Barcelona, Spain
Josep Gregori, Roche Diagnostics SL, 08174 Sant Cugat del Vallès, Spain
Damir García-Cehic, María Cubero, CIBERehd del Instituto de Salud Carlos III, Liver Unit Internal Medicine, Lab Malalties Hepatiques, VHIR-HUVH, 08035 Barcelona, Spain
Rosario Casillas, Liver Unit and Biochemistry Department, HUVH, 08035 Barcelona, Spain
Author contributions: Quer J, Esteban R, Guàrdia J, Buti M, Esteban JI, Rodríguez-Frías F and Oubiña JR designed the research and participated in the discussion, analysis of results and manuscript preparation; Quer J, del Pino N, Otero T, García-Cehic D, Cubero M, Camos S and Casillas R performed the real-time-nested polymerase chain reaction amplifications and sequencing research; Quer J and Gregori J performed the alignments and phylogenetic analysis; del Pino N collected the samples.
Supported by Argentinian Fresenius Medical Care Centre, Spanish Ministry of Science and Innovation (MINECO) Grants, SAF2009-10403; and Spanish Ministry of Health (FIS), PI10/01505 and 09/0899
Correspondence to: Josep Quer, PhD, Senior Researcher, CIBERehd del Instituto de Salud Carlos III, Autonomous University of Barcelona and Liver Unit, Internal Medicine, Lab. Malalties Hepatiques, Vall d’Hebron Institut de Recerca (VHIR) Hospital Universitari Vall d’Hebrón (HUVH) 119129, 08035 Barcelona, Spain. josep.quer@vhir.org
Telephone: +34-934-894028 Fax: +34-934-894032
Received: January 22, 2013
Revised: April 30, 2013
Accepted: July 4, 2013
Published online: September 21, 2013
Abstract

AIM: To study the subtype prevalence and the phylogenetic relatedness of hepatitis C virus (HCV) sequences obtained from the Argentine general population, a large cohort of individuals was analyzed.

METHODS: Healthy Argentinian volunteers (n = 6251) from 12 provinces representing all geographical regions of the country were studied. All parents or legal guardians of individuals younger than 18 years provided informed written consent for participation. The corresponding written permission from all municipal authorities was obtained from each city or town where subjects were to be included. HCV RNA reverse transcription-polymerase chain reaction products were sequenced and phylogenetically analyzed. The 5’ untranslated region (5’UTR) was used for RNA detection and initial genotype classification. The NS5B polymerase region, encompassing nt 8262-8610, was used for subtyping.

RESULTS: An unexpectedly low prevalence of HCV infection in the general population (0.32%) was observed. Our data contrasted with previous studies that reported rates ranging from 1.5% to 2.5%, mainly performed in selected populations of blood donors or vulnerable groups. The latter values are in keeping with the prevalence reported by the 2007 Argentinian HCV Consensus (approximately 2%). HCV subtypes were distributed as follows: 1a (25%), 1b (25%), 2c (25%), 3a (5%), and 2j (5%). Two isolates ascribed either to genotype 1 (5%) or to genotype 3 (5%) by 5’UTR phylogenetic analysis could not be subtyped. Subtype 1a sequences comprised a highly homogeneous population and clustered with United States sequences. Genotype 1b sequences represented a heterogeneous population, suggesting that this genotype might have been introduced from different sources. Most subtype 2c sequences clustered close to the 2c reported from Italy and Southern France.

CONCLUSION: HCV has a low prevalence of 0.32% in the studied general population of Argentina. The pattern of HCV introduction and transmission in Argentina appears to be a consequence of multiple events and different for each subtype.

Keywords: Hepatitis C virus NS5B subtyping; Molecular epidemiology; Hepatitis C virus; Argentina; Hepatitis C virus 5’ untranslated region

Core tip: This study reports an unexpectedly low prevalence of hepatitis C virus (HCV) (0.32%) in the general population of Argentina, with a subgenotype distribution of 1a (25%), 1b (25%), 2c (25%), 3a (5%), and 2j (5%) while two isolates ascribed either to genotype 1 (5%) or to genotype 3 (5%) could not be subtyped. Phylogenetic analysis of the NS5B region has enabled us to define the pattern of HCV introduction and transmission in Argentina as a consequence of multiple events that differed for each (sub)genotype studied. Furthermore, this report discusses the putative sources of HCV subgenotype introduction in Argentina.