Abstract
Hepatitis C virus (HCV) is a causative agent of chronic liver disease, cirrhosis, and hepatocellular carcinoma. It constitutes a major public health around the world. There is no vaccine available against HCV, and current therapies are effective in only small percentage of patients. HCV has wide population-specific genotype variability. Genotype knowledge and viral load assessment are equally important for designing therapeutic strategies. Taking into account that the molecular epidemiology of HCV variants circulating in Tunisia is not yet well elucidated, and that, at present, little is known about the distribution pattern of HCV in Monastir region (Tunisia), we aimed, herein, to evaluate the prevalence of HCV genotypes in Monastir and to identify risk-related factors. For this purpose, 50 anti-HCV antibody-positive cases were diagnosed and subjected to viral RNA extraction, amplification, genotyping, and viral load quantification. Molecular epidemiology was studied by 5′ untranslated region (5′ UTR) sequencing as compared with the non-structural 5B (NS5B) and core region sequences. Overall concordance between 5′ UTR, core, and NS5B sequencing was 100 %. The highest prevalent genotype was 1b (50 %) followed by genotypes 1a (16 %), 4a (12 %), 2a (10 %), 2c (8 %), and 3a (4 %). Interestingly, the subtype 1b had a statistically significant higher viral load than the other genotypes followed by subtype 1a. Based on these data, this study revealed a high prevalence of HCV genotype 1 (subtypes 1b and 1a) compared to other genotypes. A continued monitoring of HCV and knowledge of circulating genotypes could impact on future vaccine formulations.
Similar content being viewed by others
References
Ackerman Z, Ackerman E, Paltiel O (2000) Intrafamilial transmission of hepatitis C virus: a systematic review. J Viral Hepat 7:93–103
Aktaş E, Ogedey ED, Külah C, Beğendik Cömert F (2010) Hepatitis C virus genotypes in a province of western Black-Sea region, Turkey. Mikrobiyol Bul 44:647–650
Alagöz GK, Karataylı SC, Karataylı E, Çelik E, Keskin O, Dinç B, Çınar K, İdilman R, Yurdaydın C, Bozdayı AM (2014) Hepatitis C virus genotype distribution in Turkey remains unchanged after a decade: performance of phylogenetic analysis of the NS5B, E1, and 5′UTR regions in genotyping efficiency. Turk J Gastroenterol 25:405–410
Ansari M, Lingaiah R, Irshad M (2012) HCV-core region: its significance in HCV genotyping and type dependent genomic expression. MJMS 5:30–39
Antaki N, Craxi A, Kamal S, Moucari R, Van der Merwe S, Haffar S, Gadano A, Zein N, Lai CL, Pawlotsky JM, Heathcote EJ, Dusheiko G, Marcellin P (2010) The neglected hepatitis C virus genotypes 4, 5 and 6: an international consensus report. Liver Int 30:342–355
Asada A, Shioya M, Osaki R, Nishimura T, Takeuchi T, Okumura Y, Andoh A (2015) MHC class I-related chain B gene polymorphism is associated with virological response to pegylated interferon plus ribavirin therapy in patients with chronic hepatitis C infection. Biomed Rep 3:247–253
Ashraf A, Chakravarti A, Malik S (2013) A study of changing trends of prevalence and genotypic distribution of hepatitis C virus among high risk groups in North India. Indian J Med Microbiol 31:354–359
Athar MA, Xu Y, Xie X, Xu Z, Ahmad V, Hayder Z, Ali SS, Liao Y, Li Q (2015) Rapid detection of HCV genotyping 1a, 1b, 2a, 3a, 3b and 6a in a single reaction using two-melting temperature codes by a real-time PCR-based assay. J Virol Methods 222:85–90
Ayed K, Gorgi Y, Ben Abdallah T et al (2003) Hepatitis C virus infection in hemodialysis patients from Tunisia: national survey by serological and molecular methods. Transpl Proc 35:2573–2575
Baclig MO, Chan VF, Ramos JDA, Gopez-Cervantes J, Natividad FF (2010) Correlation of the 5′untranslated region (5′UTR) and non-structural 5B (NS5B) nucleotide sequences in hepatitis C virus subtyping. Int J Mol Epidemiol Genet 1:236–244
Bhattacharjee D, Mukherjee K, Chakroborti G, Ghosh R, Mandal N, Bose M (2015) Correlation study between HCV genotypes distribution pattern and viral load in a tertiary care hospital in Kolkata, India. J Clin Diagn Res 9:DC15–DC17
Carneiro MA, Teles SA, Dias MA, Ferreira RC, Naghettine AV, Silva SA, Lampe E, Yoshida CF, Martins RM (2005) Decline of hepatitis C infection in hemodialysis patients in Central Brazil: a ten years of surveillance. Mem Inst Oswaldo Cruz 100:345–349
da Silva NMO, Germano FN, Mendoza-Sassi RA, Seuánez HN, Soares MA, de Martinez AMB (2013) Evidence of association between hepatitis C virus genotype 2b and nosocomial transmissions in hemodialysis centers from southern Brazil. Virol J 10:167
di Filippo D, Cortes-Mancera F, Beltran M, Arbelaez MP, Jaramillo S, Restrepo JC, Correa G, Navas MC (2012) Molecular characterization of hepatitis C virus in multi-transfused Colombian patients. Virol J 9:242
Djebbi A, Bahri O, Langar H, Sadraoui A, Mejri S, Triki H (2008) Genetic variability of genotype 1 hepatitis C virus isolates from Tunisian haemophiliacs. New Microbiol 31:473–480
Djebbi A, Triki H, Bahri O et al (2003) Genotypes of hepatitis C virus circulating in Tunisia. Epidemiol Infect 130:501–505
Fabrizi F, Bunnapradist S, Lunghi G, Martin P (2003) Kinetics of hepatitis C virus load during hemodialysis: novel perspectives. J Nephrol 16:467–475
Hara K, Rivera MM, Koh C, Sakiani S, Hoofnagle JH, Heller T (2013) Important factors in reliable determination of hepatitis C virus genotype by use of the 5′ untranslated region. J Clin Microbiol 51:1485–1489
Hmida S, Mojaat N, Chaouachi E, Mahjoub T, Abid S, Boukef K (1995) HCV antibodies in hemodialyzed patients in Tunisia. Pathol Biol 43:581–583
Jacka B, Lamoury F, Simmonds P, Dore GJ, Grebely J et al (2013) Sequencing of the hepatitis C virus: a systematic review. PLoS One 8:e67073
Jun DW, Tak WY, Bae SH, Lee YJ (2012) Recent trends in the treatment of chronic hepatitis C. Korean J Hepatol 18:22–28
Kchouk FH, Gorgi Y, Bouslama L, Sfar I, Ayari R, Khiri H, Halfon P, Aouadi H, Jendoubi Ayed S, Ayed K, Ben Abdallah T (2013) Phylogenetic analysis of isolated HCV strains from tunisian hemodialysis patients. Viral Immunol 26:40–48
Li HC, Lo SY (2015) Hepatitis C virus: virology, diagnosis and treatment. World J Hepatol 7:1377–1389
Lole KS, Jha JA, Shrotri SP, Tandon BN, Prasad VG, Arankalle VA (2003) Comparison of hepatitis C virus genotyping by 5′ noncoding region and core-based reverse transcriptase PCR assay with sequencing and use of the assay for determining subtype distribution in India. J Clin Microbiol 41:5240–5244
Minami T, Kishikawa T, Sato M, Tateishi R, Yoshida H, Koike K (2013) Meta-analysis: mortality and serious adverse events of peginterferon plus ribavirin therapy for chronic hepatitis C. J Gastroenterol 48:254–268
Nabi SG, Zaffar G, Sheikh NI, Hassan K, Hassan U (2013) Hepatitis C virus genotypes: a plausible association with viral loads. Indian J Pathol Microbiol 56:384–387
Nakatani SM, Santos CA, Riediger IN, Krieger MA, Duarte CA, do Carmo Debur M, Carrilho MFJ, Ono SK (2011) Comparative performance evaluation of hepatitis C virus genotyping based on the 5′ untranslated region versus partial sequencing of the NS5B region of Brazilian patients with chronic hepatitis C. Virol J 8:459
Nguyen LH, Nguyen MH (2013) Systematic review: asian patients with chronic hepatitis C infection. Aliment Pharmacol Ther 37:921–936
Nishiguchi S, Enomoto H, Aizawa N et al (2014) Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of Genotype 1b : a multicenter randomized trial, ReGIT-J study. J Gastroenterol 49:492–501
Oh DJ, Park YM, Seo YI, Lee JS, Lee JY (2012) Prevalence of hepatitis C virus infections and distribution of hepatitis C virus genotypes among Korean blood donors. Ann Lab Med 32:210–215
Oliveira CV, Barbosa WF, Silveira LVA, Menezes J, Machado FS, Silva GF (2015) Prevalence of the hepatitis C virus among university employees in São Paulo, Southeastern Brazil: predictive factors and geoprocessing spatial analysis. Arq Gastroenterol 52:9–13
Patel PR, Thompson ND, Kallen AJ, Arduino MJ (2010) Epidemiology, surveillance, and prevention of hepatitis C virus infections in hemodialysis patients. Am J Kidney Dis 56:371–378
Pawlotsky JM (2003) Mechanism of antiviral treatment efficacy and failure in chronic hepatitis C. Antiviral Res 59:1–11
Quer J, Gregori J, Rodríguez-Frias F, Buti M, Madejon A, Perez-del-Pulgar S, Garcia-Cehic D, Casillas R, Blasi M, Homs M, Tabernero D, Alvarez-Tejado M et al (2015) High-resolution hepatitis C virus subtyping using NS5B deep sequencing and phylogeny, an alternative to current methods. J Clin Microbiol 53:219–226
Sandres-Saune K, Deny P, Pasquier C, Thibaut V, Duverlie G, Izopet J (2003) Determining hepatitis C genotype by analyzing the sequence of the NS5B. J Virol Methods 109:187–193
Scheel TK, Rice CM (2013) Understanding the hepatitis C virus life cycle paves the way for highly effective therapies. Nat Med 19:837–849
Simmonds P (2004) Genetic diversity and evolution of hepatitis C virus-15 years on. J Gen Virol 85:3173–3188
Sinn DH, Kim YJ, Lee ST et al (2011) Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in Asian patients. J Gastroenterol Hepatol 26:1374–1379
Smith DB, Bukh J, Kuiken C, Muerhoff AS, Rice CM, Stapleton JT, Simmonds P (2014) Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: updated criteria and assignment web resource. Hepatology 59:318–327
Thong VD, Akkarathamrongsin S, Poovorawan K, Tangkijvanich P, Poovorawan Y (2014) Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication. World J Gastroenterol 20:2927–2940
Verbeeck J, Stanley MJ, Shieh J, Celis L, Huyck E, Wollants E, Morimoto J, Farrior A, Sablon E, Jankowski-Hennig M, Schaper C, Johnson P, Van Ranst M, Van Brussel M (2008) Evaluation of versant hepatitis C virus genotype assay (LiPA) 2.0. J Clin Microbiol 46:1901–1906
World Health Organization (1999) Global surveillance and control of hepatitis C: report of a WHO consultation organized in collaboration with the viral hepatitis prevention board, antwerp, belgium. J Viral Hepat 6:35–47
World Health Organization (1997) Hepatitis C: global prevalence. Wkly Epidemiol Rec 72:341–344
Yamashita N, Ohho A, Yamasaki A, Kurokawa M, Kotoh K, Kajiwara E (2014) Hepatocarcinogenesis in chronic hepatitis C patients achieving a sustained virological response to interferon: significance of lifelong periodic cancer screening for improving outcomes. J Gastroenterol 49:1504–1513
Yang CS, Chang HH, Chou CC, Peng SJ (2003) Isolation effectively prevents the transmission of hepatitis C virus in the hemodialysis unit. J Formos Med Assoc 102:79–85
Acknowledgments
The authors would like to acknowledge the contribution of participating patients. This study was funded by the French Institute of Tunisia in collaboration with Campus France—The National Agency for the Promotion of French Higher Education Abroad, as a part of scientific scholarship senior (Séjour Scientifique de Haut Niveau “SSHN” 2015).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Souii, A., Elargoubi, A., Fallecker, C. et al. Hepatitis C Genotype Prevalence in Monastir Region, Tunisia: Correlation between 5′ Untranslated Region (5′UTR), Non-structural 5B (NS5B), and Core Sequences in HCV Subtyping. Curr Microbiol 73, 324–334 (2016). https://doi.org/10.1007/s00284-016-1064-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00284-016-1064-2