Abstract
BackgroundHepatitis C virus (HCV) infection is a global health problem estimated to affect almost 200 million people worldwide. The aim of this study is to analyze the subtypes and existence of variants resistant to protease inhibitors and their association with potential HCV risk factors among blood donors in Brazil.MethodsRepeat anti-HCV reactive blood donors are systematically asked to return for retest, notification, and counseling in which they are interviewed for risk factors for transfusion-transmitted diseases. We analyzed 202 donors who returned for counseling from 2007 to 2010 and presented enzyme immunoassay- and immunoblot-reactive results. The HCV genotypes and resistance mutation analyses were determined by the direct sequencing of the NS5b and NS3 regions, respectively. The HCV viral load was determined using an in-house real-time PCR assay targeting the 5′-NCR.ResultsHCV subtypes 1b, 1a, and 3a were found in 45.5%, 32.0%, and 18.0% of the donors, respectively. The mean viral load of genotype 1 was significantly higher than that of the genotype 3 isolates. Subtype 1a was more frequent among young donors and 3a was more frequent among older donors. Protease inhibitor-resistant variants were detected in 12.8% of the sequenced samples belonging to genotype 1, and a higher frequency was observed among subtype 1a (20%) in comparison to 1b (8%). There was no difference in the prevalence of HCV risk factors among the genotypes or drug-resistant variants.ConclusionsWe found a predominance of subtype 1b, with an increase in the frequency of subtype 1a, in young subjects. Mutations conferring resistance to NS3 inhibitors were frequent in treatment-naïve blood donors, particularly those infected with subtype 1a. These variants were detected in the major viral population of HCV quasispecies, have replicative capacities comparable to nonresistant strains, and could be important for predicting the response to antiviral triple therapy.
Highlights
Hepatitis C virus (HCV) was identified by Choo et al in 1989 [1] and is currently a major cause of chronic hepatitis in the world, with almost 200 million carriers (2–3% of the global population) and approximately 350,000 deaths annually [2].Blood transfusion, contaminated blood products, and unsafe medical practices were the main routes of global HCV spread after the Second World War until the early 1980s [3]
HCV prevalence is decreasing among blood donors, and de Almeida-Neto et al found a low HCV prevalence (0.19%) in three large Brazilian blood centers in 2013, which could be due to improvements in blood donor selection and in the social and economic conditions of the population [19]
The HCV genotypes were determined by NS5b amplification, and sequencing was successful in all 178 RNA-detectable samples; of these, 45.5% (81/178) were typed as 1b, 32.0% (57/178) as 1a, 18.0% (32/178) as 3a, and 4.5% (8/178) as others (2b (5/8), 2c (1/ 8), 4 (1/8), and 5 (1/8))
Summary
HCV was identified by Choo et al in 1989 [1] and is currently a major cause of chronic hepatitis in the world, with almost 200 million carriers (2–3% of the global population) and approximately 350,000 deaths annually [2].Blood transfusion, contaminated blood products, and unsafe medical practices were the main routes of global HCV spread after the Second World War until the early 1980s [3]. HCV was identified by Choo et al in 1989 [1] and is currently a major cause of chronic hepatitis in the world, with almost 200 million carriers (2–3% of the global population) and approximately 350,000 deaths annually [2]. The introduction of screening tests for blood donors reduced the risk of transfusion-transmitted HCV [4], the use of illicit intravenous drugs remains one of the major risk factors for HCV infection [5]. In Brazil, the prevalence of HCV infection may reach 11% in IVDUs [8,9], is approximately 1.5% in the general population [10,11,12], and ranges from 0.21% to 1.1% in blood donors [13,14,15,16,17,18].
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