Received: 05.06.2011 Accepted: 16.08.2011 J Gastrointestin Liver Dis September 2011 Vol. 20 No 3, 261-266 Address for correspondence: Simona Ruta Chair of Virology, University of Medicine and Pharmacy Bucharest Romania Email: simona@simonaruta.ro molecular Epidemiology of Hepatitis C Virus Strains from Romania Camelia Sultana 1,2* , Gabriela Oprisan 3* , Camelia Szmal 3 , Codruta Vagu², Aura Temereanca 1,2 , Sorin Dinu³, Monica Delia Teleman 4 , Simona Ruta 1,2 1) Chair of Virology, Carol Davila University of Medicine and Pharmacy; 2) Emergent Disease Department, Stefan S. Nicolau Institute of Virology; 3) Molecular Epidemiology Laboratory, NIRDMI Cantacuzino; 4) Department of Microbiology and Epidemiology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania * C. Sultana and G. Oprisan contributed equally to this work. Abstract Background & Aims: A high seroprevalence of Hepatitis C Virus (HCV) infection has been reported in Romania, with limited data on the viral subtypes’ distribution. In order to detect any changes in the genetic composition of the epidemic, a survey on the recent profile of circulating HCV genotypes was conducted. methods: 241 hepatitis C infected patients with active viral replication diagnosed between September 2004 - October 2008 were included in a retrospective study. Genotyping using commercial Line Probe Assay (Innogenetics) was confirmed by sequencing of Core PCR products followed by phylogenetic analysis. Results: HCV subtype 1b was found in 92.6% of the samples, subtype 1a in 5.4 % of the samples, subtype 4a in 1.2%, and subtype 3a in 0.8% of the samples. Chronic hepatitis C infections with subtype 1b were found in women aged 40-60 years old with a history of blood transfusions received during surgical/obstetrical interventions. No geographical clustering was evident for HCV 1b sequences. The new emerging non-1b genotypes were detected mainly in younger patients with a history of intravenous drug use. The genetic distances among the HCV 1a strains are very homogeneous and small, with a high sequence identity with other European strains, suggesting the recent entrance of this subtype in Romania from singular or limited sources of infection. Conclusion: The introduction of new HCV genotypes in Romania stimulates a continuous epidemiological surveillance, suggesting shifts in the transmission pathways and risk factors, with the possible emergence of recombinant strains in patients with multiple infections. Key words Hepatitis C virus – genotyping methods – molecular epidemiology – risk factors. Introduction Hepatitis C virus (HCV) is the subject of intense research and clinical investigations due to its worldwide prevalence and major role in chronic liver disease. Phylogenetic analysis of HCV genomes has led to a classification of HCV into six different genotypes that differ from each other by 31%- 33% on the nucleotide level, and have a regional specific distribution, genotypes 1a and 1b being the most frequently encountered in Europe, United States, and Japan. HCV subtypes 2a and 2b are commonly found in North America, subtype 2c in Northern Italy, while genotype 4 is predominant in North Africa (especially in Egypt) and the Middle East; genotypes 5 and 6 are commonly reported in South Africa and Hong Kong, respectively. Genotype 3a is endemic in South East Asia, and seems to be dominant in intravenous drug users (IDUs) in Europe and the United States [1]. Viral genotype is the most important factor in assessing the optimal treatment duration for HCV infection, with additional guidance provided by the on-treatment response, rapid virological response being an earlier predictor of treatment success, and early virological response - an accurate marker of treatment failure. HCV genotypes can be ranked, in a decreasing order of susceptibility to interferon- based treatment, as follows: genotypes 2, 3, 4 and 1 [2, 3]. In the latter years it has been reported that, especially in genotypes 1 and 4, single nucleotide polymorphisms (SNPs) located near the gene for interleukin-28B (IL28B) are strongly associated with the likelihood of achieving a sustained virological response [4, 5], as well as with the viral kinetics during treatment [6], and the natural clearance of HCV infection [7]. Infection with HCV genotype 1b has been strongly associated with more severe liver disease and higher risk for the development of hepatocellular carcinoma than infection with other HCV genotypes [8]. HCV genotype 3 was recently associated with faster fibrosis progression compared to other genotypes [9, 10].