Epidemic history of hepatitis C virus genotypes and subtypes in Portugal

Abstract

Any successful strategy to prevent and control HCV infection requires an understanding of the epidemic behaviour among the different genotypes. Here, we performed the first characterization of the epidemic history and transmission dynamics of HCV subtypes in Portugal. Direct sequencing of NS5B was performed on 230 direct-acting antiviral drugs (DAA)-treatment naïve patients in Lisbon. Phylogenetic analysis was used for subtyping and transmission cluster identification. Bayesian methods were used to reconstruct the epidemic history of HCV subtypes. Sequences were analysed for resistance-associated substitutions (RAS). The majority of strains were HCV-GT1 (62.6%), GT3 (18.3%, all subtype 3a) and GT4 (16.1%). Among GT1, the most frequent were subtypes 1a (75.5%) and 1b (24.5%). Polyphyletic patterns were found in all but 12 lineages suggesting multiple introductions of the different subtypes in this population. Five distinct epidemics were identified. The first significant HCV epidemic in Portugal occurred between 1930s and 1960s, was caused almost exclusively by GT1b and was likely associated with blood transfusions. Rapid expansion of GT3a occurred in the 1960s and GT1a in the 1980s, associated with intravenous drug use. The most recent epidemics were caused by GT4a and GT4d and seem to be associated with the resurgence of opioid use. The C316N substitution was found in 31.4% of GT1b-patients. Close surveillance of patients bearing this mutation and undergoing dasabuvir-based regimens will be important to determine its impact on treatment outcome.

Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort

“…The patients included did not present significant differences regarding the demographic characteristics and comorbidity prevalence when compared with other cohorts [4,[18][19][20]. The most prevalent HCV genotype was genotype 1, followed by genotype 3, matching recent epidemiological studies on the geographical distribution of HCV in Portugal [21,22]. On the other hand, we had a lower proportion of CP-B/C patients at baseline.…”

Epidemic history and baseline resistance to NS5A-specific direct acting drugs of hepatitis C virus in Spain

“…Phylogenetic analysis confirmed the presence of two divergent GT1a clades, clades I and II 39 . Consistent with our previous observations, clade II showed a prevalence more than fourfold higher than clade I 13 , 26 . These findings illustrate the distinct geographic distributions of these GT1a clades, since clade I is more common in the United States and both clades are identically represented in other European countries 40 , 41 .…”

“…Next, a maximum likelihood tree was built using IqTree 24 and a temporal signal analysis was performed using Tempest 25 . The Bayesian analysis was carried out as described formerly 26 . Briefly, the SRD06 model of nucleotide substitution 27, and an uncorrelated lognormal relaxed molecular clock (UCLD) with a Bayesian skyline plot (BSP) coalescent prior were specified in BEAUti in the BEAST package.…”

<p>Deep-sequencing study of HCV G4a resistance-associated substitutions in Egyptian patients failing DAA treatment</p>

“…However, alignment of the patients’ sequences with the consensus G4a sequence, composed of isolates downloaded from the Los Alamos database, identified two NS5B amino acid substitutions (A235V/T, R304K) with an unknown RAS effect. Specifically, all three patients were carrying the A235V substitution in almost all reads (99.3–100%), whereas R304K, reported at baseline in Portuguese G4a patients,12 was prevalent in patient 3.…”