Abstract
Hepatitis C virus subtype 1b (HCV1b) is still the most prevalent subtype worldwide, with massive expansion due to poor health care standards, such as blood transfusion and iatrogenic procedures. Despite safe and effective new direct antiviral agents (DAA), treatment success can depend on resistance-associated substitutions (RASs) carried in target genomic regions. Herein we investigated transmission clusters and RASs among isolates from HCV1b positive subjects in the Calabria Region. Forty-one NS5B and twenty-two NS5A sequences were obtained by Sanger sequencing. Phylogenetic analysis was performed using the maximum likelihood method and resistance substitutions were analyzed with the Geno2pheno tool. Phylogenetic analysis showed sixteen statistically supported clusters, with twelve containing Italian sequences mixed with foreign HCV1b isolates and four monophyletic clusters including only sequences from Calabria. Interestingly, HCV1b spread has been maintained by sporadic infections in geographically limited areas and by dental treatment or surgical intervention in the metropolitan area. The L159F NS5B RAS was found in 15 isolates and in particular 8/15 also showed the C316N substitution. The Y93H and L31M NS5A RASs were detected in three and one isolates, respectively. The A92T NS5A RAS was found in one isolate. Overall, frequencies of detected NS5B and NS5A RASs were 36.6% and 22.7%, respectively. For the eradication of infection, improved screening policies should be considered and the prevalence of natural RASs carried on viral strains.
Highlights
Hepatitis C (HCV) infection remains a major public health problem, even if in the last few years HCV therapy has been improved by the availability of direct-acting antiviral (DAA) agents [1]
Viral isolates collected between 2015 and 2016 from naïve and IFN/pegIFN-α/RBV treated patients were analyzed in the NS5B and NS5A regions to assess the presence of resistance-associated substitutions (RASs) with the potential to impact on direct antiviral agents (DAA) therapy
Hepatitis C virus subtype 1b (HCV1b) diffusion worldwide is related to several risk factors, such as blood transfusions, dental treatment, unsafe reuse of nondisposable syringes [27,28]
Summary
Hepatitis C (HCV) infection remains a major public health problem, even if in the last few years HCV therapy has been improved by the availability of direct-acting antiviral (DAA) agents [1]. Phylogenetic analyses have identified eight HCV major genotypes, further subdivided into 67 subtypes [2]. HCV1b is widespread all over the world, HCV2 showed higher prevalence in Russia and in Italy. In Europe, the most common HCV2 subtypes are HCV2a/2c. HCV1a and HCV3a predominate in Europe and North America, while HCV4 is endemic in the Middle East, Central Africa and Mediterranean countries. HCV5 is endemic in South Africa, HCV6 in South East Asia and HCV7 was found in the Democratic Republic of Congo. Magiorkinis and colleagues reported a massive expansion of HCV1b infections between 1940 and 1980, sustained by blood transfusion and iatrogenic procedures [5]
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