High incidence of the hepatitis C virus recombinant 2k/1b in Georgia: Recommendations for testing and treatment

Abstract

Aim The first hepatitis C virus (HCV) recombinant, RF2k/1b, was initially described from Russia and has since then been identified from patients in Ireland, Estonia, Uzbekistan and Cyprus. Many of these patients originated from Georgia; however there is no information on its prevalence in Georgia or its susceptibility to antiviral treatment. Methods We retrospectively sequenced the non-structural region 5B (NS5B) of the HCV genome in samples from 72 Georgian patients, 36 of those had been treated with Pegylated Interferon and Ribavirin. Results The HCV genotype was determined using the Versant HCV Genotype v2 kit. Based on this typing, 32 patients (44.4%) were infected with genotype 1, 21 (29.1%) genotype 2 and 19 (26.3%) genotype 3. Partial NS5B of these strains was sequenced and analyzed for type, with concordant genotype results for all type 1 and 3 strains. Discrepant results were observed for genotyped 2 strains, with 16 (76%) having NS5B of subtype 1b. On phylogenetic analysis, 15 NS5B sequences of these strains were found in a clade formed by recombinant RF2k/1b stains. The remaining discordant sequence was found within a clade formed by 1b strains. Conclusion Our findings show that the RF2k/1b recombinant strain is common among Georgian patients previously assumed to be infected by genotype 2. Since genotyping is mainly performed to decide treatment strategies; there is a need to determine the genotype by analysis of at least two genomic regions in strains from Georgian patients considered infected by genotype 2 based on standard HCV genotyping methods.

Global epidemiology of HCV subtypes and resistance-associated substitutions evaluated by sequencing-based subtype analyses

“…Assays that focus on a short part of the genome may not discern correct genotypes if there is high sequence homology, and are limited in identification of recombinant and/or novel strains (15,16). Amplicon and full genome sequencing of HCV are alternate methods that provide greater resolution in the identification of genotype and subtype (16).…”

“…The prevalence of recombinant forms of HCV, detected in Eastern Europe and Russia (15)(16)(17), are not known on a global scale. Identification of recombinant sequences will inform the global prevalence of known recombinant viruses, like RF2k/1b, and potentially identify new recombinant forms in the population.…”

Potential risk of misclassification HCV 2k/1b strains as HCV 2a/2c using VERSANT HCV Genotype 2.0 assay

“…The recombinant genotype 2k/1b was first described in St Petersburg in 2002 in intravenous (IV) drug users (Kalinina et al, 2002). Since its discovery, the genotype 2k/1b has been detected in many countries, including Ireland, Uzbekistan, Cyprus, France, the Netherlands, and Russia (Demetriou et al, 2009;Kalinina et al, 2002;Karchava et al, 2015;Kurbanov et al, 2008aKurbanov et al, , 2008bMoreau et al, 2006;Morel et al, 2010;Raghwani et al, 2012). In all these cases, the patients originated from Russia or Georgia.…”

Molecular Epidemiology Features of Hepatitis C Virus Isolates From Different Regions of the Republic Sakha (Yakutia)

“…Анализ генотипов по-казал преобладание на территории Грузии ге-нотипа 1 (42,0%) по сравнению с генотипами 3 (32,9%) и 2 (24,9%). У нескольких пациентов (0,1%) был выявлен генотип 4 [24]. ВГС гено-типа 1 субтипа 1b также преобладает в Узбеки-стане (64,2%), субтип 3а встречается в Узбеки-стане с частотой 25,0%, субтипы 2а, 1а, 2б и 3б были выявлены в 3,8; 2,9; 2,9 и 1,0% случаев со-ответственно [28].…”