Molecular epidemiology and putative origin of hepatitis C virus in random volunteers from Argentina

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 weredistributed 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.Genotype1b 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.

ACE Score Identifies HBeAg-negative Inactive Carriers at a Single-point Evaluation,Regardless of HBV Genotype

Background and Aims:Hepatitis B virus(HBV)biomark-ers have been used for a better categorization of patients,even though the lack of simple algorithms and the impact of genotypes limit their application.Our aim was to assess the usefulness of noninvasive markers for the identification of HBV inactive carriers(ICs)in a single-point evaluation and to design a predictive model for their identification.Meth-ods:This retrospective-prospective study included 343 consecutive HBeAg-negative individuals.Clinical,analytical,and virological data were collected,and a liver biopsy was performed if needed.Subjects were classified at the end of follow-up as ICs,chronic hepatitis B and gray zone.A pre-dictive model was constructed,and validated by 1000-boot-strap samples.Results:After 39 months of follow-up,298 subjects were ICs,36 were chronic hepatitis B CHB,and nine were gray zone.Eighty-nine(25.9%)individuals re-quired a liver biopsy.Baseline HBV DNA hazard ratio(HR)6.0,p<0.001),HBV core-related antigen(HBcrAg)(HR 6.5,p<0.001),and elastography(HR 4.6,p<0.001)were inde-pendently associated with the IC stage.The ACE score(HBV DNA,HBcrAg,elastography),obtained by bootstrapping,yielded an area under the receiver operating characteris-tics(AUROC)of 0.925(95%CI:0.880-0.970,p<0.001)for identification of ICs.The AUROC for genotype D was 0.95,0.96 for A,0.90 for E,and 0.88 for H/F.An ACE score of<1 had a positive predictive value of 99.5%,and a score≤12 points had a diagnostic accuracy of 93.8%.Conclusions:Low baseline HBV DNA,HBcrAg,and liver stiffness were in-dependently associated with the IC phase.A score including those variables identified ICs at a single-point evaluation,and might be applied to implement less intensive follow-up strategies.