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Hepatitis viruses take advantage of traditional practices to increase the burden of hepatocellular carcinoma in Tunisia

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Abstract

Hepatocellular carcinoma (HCC) is a major public health issue in Africa. In Tunisia, hepatitis B virus (HBV) is known to be an important risk factor for HCC in the south of the country, but the role played by hepatitis C virus (HCV) still remains unclear. The aim of the current case-control study was to identify risk factors for HCC development in the northern part of the country. Clinical and biological data including viral hepatitis status (serological and molecular) and non-infectious risk factors from 73 patients with HCC and 70 control subjects without hepatic diseases were collected. The mean age of the patients was 63 ± 10 years, and the ratio of males to females was 1.1. HCC occurred in cirrhotic liver in 72.0% of the cases. HCV infection was the dominant risk factor (64.3% of cases); the presence of HBV was observed in 53.4% of the cases. Occult hepatitis B and C were implicated, respectively, in 30.1% and 9.6% of the cases. HCV genotype 1b was predominant. Patients originating from western Tunisia formed a homogeneous group, characterized by significantly higher rates of tattoos or scarifications (83%) and HCV infection (80%) than those from other parts of the country. Chronic HCV infection is currently the primary risk factor for HCC in Tunisia; HBV infection remains frequent in its overt or occult infection forms. Traditional esthetic practices apparently contribute to increasing the burden of terminal liver diseases in western Tunisia.

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References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127:2893–2917

    CAS  PubMed  Google Scholar 

  2. Mittal S, El-Serag HB (2013) Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol 47:S2–S6

    PubMed  PubMed Central  Google Scholar 

  3. Levero M (2006) Viral hepatitis and liver cancer: the case of hepatitis C. Oncogene 25:3834–3847

    Google Scholar 

  4. Venook AP, Papandreou C, Furuse J, de Guevara LL (2010) The incidence and epidemiology of hepatocellular carcinoma: a global and regional perspective. Oncologist 4:5–13

    Google Scholar 

  5. Güthle M, Dollinger MM (2014) Epidemiology and risk factors of hepatocellular carcinoma. Radiologe 54:654–659

    PubMed  Google Scholar 

  6. Allain JP (2005) Occult hepatitis B virus infection. Hep B Annual 2:14–30

    Google Scholar 

  7. DeMitri MS, Cassini R, Bernardi M (2010) Hepatitis B virus-related hepatocarcinogenesis: molecular oncogenic potential of clear or occult infections. Eur J Cancer 46:2178–2186

    CAS  Google Scholar 

  8. Morales-Romero J, Vargas G, García-Román R (2014) Occult HBV infection: a facelessenemy in liver cancer development. Viruses 8:1590–1611

    Google Scholar 

  9. Registre des cancers Nord-Tunisie 1993–2003. Institut national de la santé publique. Ministère de la santé publique

  10. Salim EI, Moore MA, Al-Lawati JA, Al-Sayyad J, Bazawir A, Bener A et al (2009) Cancer epidemiology and control in the Arab World- past, present and future. Asian Pac J Cancer Prev 10:3–16

    PubMed  Google Scholar 

  11. Bahri O, Ezzikouri S, Alaya-Bouafif NB, Iguer F, Feydi AE, Mestiri H et al (2011) First multicenter study for risk factors for hepatocellular carcinoma development in North Africa. World J Hepatol 27:24

    Google Scholar 

  12. Said Y, Debbeche R, Ben Ali Z, Bouzid K, Trabelsi S, Bouzaidi S et al (2012) Epidemiological, clinical and therapeutic features of hepatocellular carcinoma in cirrhotic patients. Tunis Med 90:468–472

    PubMed  Google Scholar 

  13. Hefaiedh R, Elloumi H, Ouakaa A, Elloumi H, Kochlef A, Gargouri D et al (2009) Management of the hepatocellular carcinoma. Tunis Med 87:721–725

    PubMed  Google Scholar 

  14. Triki H (1994) Epidemiology of hepatitis B virus, hepatitis C virus and Delta virus in the general population and in liver cirrhosis in Tunisia. Arch Inst Pasteur Tunis 71:403

    CAS  PubMed  Google Scholar 

  15. Rajhi M, Mejri S, Djebbi A, Chouaieb S, Cheikh I, Ben Yahia A et al (2014) Subtyping genotype 2 hepatitis C viruses from Tunisia: identification of two putative new subtypes. Virus Genes 48:209–217

    CAS  PubMed  Google Scholar 

  16. Sibnarayan D et al (2008) Analysis of hepatitis B virus X gene phylogeny, genetic variability and its impact on pathogenesis: implications in Eastern Indian HBV carriers. Virology 382(2):190–198

    Google Scholar 

  17. Chemin I, Zoulim F, Merle P, Arkhis A, Chevallier M, Kay A et al (2001) High incidence of hepatitis B infections among chronic hepatitis cases of unknown a etiology. J Hepatol 31:447–454

    Google Scholar 

  18. Kew M (2013) Epidemiology of hepatocellular carcinoma in sub-Saharan Africa. Ann Hepatol 12:173–182

    PubMed  Google Scholar 

  19. Dogan E, Yalcin S, Koca D, Olmez A (2012) Clinicopathological characteristics of hepatocellular carcinoma in Turkey. Asian Pac J Cancer Prev 13:2985–2990

    PubMed  Google Scholar 

  20. Miquel M, Sopeña J, Vergara M, Gil M, Casas M, Sánchez-Delgado J et al (2012) Factors related to survival in hepatocellular carcinoma in the geographic area of Sabadell (Catalonia, Spain). Rev Esp Enferm Dig 1:242

    Google Scholar 

  21. Appel-da-Silva MC, da Silva Miozzo SA, de Azevedo DI, Tovo CV, Branco F, de Mattos AA (2016) Incidence of hepatocellular carcinoma in outpatients with cirrhosis in Brazil: a 10-year retrospective cohort study. World J Gastroenterol 14:10219

    Google Scholar 

  22. Norredam K (1977) Primary carcinoma of the liver in Malawi: a review of 24 cases. Trop Geogr Med 29:141–149

    CAS  PubMed  Google Scholar 

  23. Diop B, Denis F, Barin F (1981) Epidemiology of primary hepatocellular carcinoma in Senegal. Progress in medical virology. Fortschritte der medizinischen Virusforschung. Prog Med Virol 27:35–40

    CAS  PubMed  Google Scholar 

  24. Kashala LO, Kalengayi MM, Conne B, Kapanci Y, Frei PC, Lambert PH (1990) Histopathologic features of hepatocellular carcinoma in Zaire. Cancer 65:130–134

    CAS  PubMed  Google Scholar 

  25. Alavian SM, Haghbin H (2016) Relative importance of hepatitis B and C viruses in hepatocellular carcinoma in EMRO countries and the Middle East: a systematic review. Hepat Mon 16(3):e35106

    PubMed  PubMed Central  Google Scholar 

  26. Huang YT, Jen CL, Yang HI, Lee MH, Su J, Lu SN et al (2011) Lifetime risk and sex difference of hepatocellular carcinoma among patients with chronic hepatitis B and C. J Clin Oncol 29:3643–3650

    PubMed  PubMed Central  Google Scholar 

  27. Bosch FX, Ribes J, Borras J (1999) Epidemiology of primary liver cancer. Semin Liver Dis 19:271–285

    CAS  PubMed  Google Scholar 

  28. El Serag HB (2002) Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 36:S74–S83

    PubMed  Google Scholar 

  29. Hassan MM, Frome A, Patt YZ (2002) EL-Serag HB: rising prevalence of hepatitis C virus infection among patients recently diagnosed with hepatocellular carcinoma in the United States. J Clin Gastroenterol 35:266–299

    PubMed  Google Scholar 

  30. Perz JF, Armstrong GL, Farrington LA, Hutin YJ, Bell BP (2006) The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide. J Hepatol 45:529–538

    PubMed  Google Scholar 

  31. Okuda K, Fujimoto I, Hanai A, Urano Y (1987) Changing incidence of hepatocellular carcinoma in Japan. Cancer Res 47:4967–4972

    CAS  PubMed  Google Scholar 

  32. Deuffic S, Buffat L, Poynard T, Valleron AJ (1999) Modeling the hepatitis C virus epidemic in France. Hepatology 29:1596–1601

    CAS  PubMed  Google Scholar 

  33. Law MG (1999) Modeling the hepatitis C virus epidemic in Australia hepatitis C Virus Projections Working Group. J Gastroenterol Hepatol 14:1100–1107

    CAS  PubMed  Google Scholar 

  34. Erhardt A, Theobald I, Petry W, Röhrborn A, Heintges T, Wettstein M et al (2002) Hepatozelluläres Karzinom. Dtsch Med Wochenschr 127:2665–2668

    CAS  PubMed  Google Scholar 

  35. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB (2004) Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study. Gastroenterology 127:1372–1380

    PubMed  Google Scholar 

  36. El-Zayadi AR, Badran HM, Barakat EM, Attia Mel D, Shawky S, Mohamed MK et al (2005) Hepatocellular carcinoma in Egypt: a single center study over a decade. World J Gastroenterol 11:5193

    PubMed  PubMed Central  Google Scholar 

  37. Hajarizadeh B, Grebely J, Dore GJ (2013) Epidemiology and natural history of HCV infection. Nature reviews. Nat Rev Gastroenterol Hepatol 10:553–562

    CAS  PubMed  Google Scholar 

  38. Kirk GD, Lesi OA, Mendy M, Akano AO, Sam O, Goedert JJ et al (2004) The Gambia Liver Cancer Study: infection with hepatitis B and C and the risk of hepatocellular carcinoma in West Africa. Hepatology 39:211–219

    PubMed  Google Scholar 

  39. Gao JD, Shao YF, Xu Y, Ming LH, Wu ZY, Liu GT et al (2005) Tight association of hepatocellular carcinoma with HBV infection in North China. Hepatobiliary Pancreat Dis Int 4:46–49

    CAS  PubMed  Google Scholar 

  40. Uzunalimoglu O, Yurdaydin C, Cetinkaya H, Bozkaya H, Sahin T (2001) Risk factors for hepatocellular carcinoma in Turkey. Dig Dis Sci 46:1022–1028

    CAS  PubMed  Google Scholar 

  41. Yaghi C, Sharara A, Rassam P, Moucari R, Honein K, BouJaoude J et al (2006) Hepatocellular carcinoma in Lebanon: etiology and prognostic factors associated with short-term survival. World J Gastroenterol 12:3575

    PubMed  PubMed Central  Google Scholar 

  42. Kremsdor FD, Soussan P, Paterlini-Brechot P, Brechot C (2006) Hepatitis B virus-related hepatocellular carcinoma: paradigms for viral-related human carcinogenesis.Oncogene 25:3823–3833

    CAS  PubMed  Google Scholar 

  43. Hayashi J, Aoki H, Arakawa Y, Hino O (1999) Hepatitis C virus and hepatocarcinogenesis. Intervirology 42:205–210

    CAS  PubMed  Google Scholar 

  44. Pineau P, Ezzikouri S, Marchio A, Benazzouz M, Cordina E, Afifi R et al (2007) Genomic stability prevails in North-African hepatocellular carcinomas. Dig Liver Dis 39:671–677

    CAS  PubMed  Google Scholar 

  45. Shawki SM, Meshaal SS, El Dash AS, Zayed NA, Hanna MO (2014) Increased DNA damage in hepatitis C virus-related hepatocellular carcinoma. DNA Cell Biol 33:884–890

    CAS  PubMed  Google Scholar 

  46. Ali A, Abdel-Hafiz H, Suhail M, Suhail M, Al-Mars A, Zakaria MK et al (2014) Hepatitis B virus, HBx mutants and their role in hepatocellular carcinoma. World J Gastroenterol 20:10238

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Raimondo G, Locarnini S, Pollicino T, Levrero M, Zoulim F, Lok AS (2019) Update of the statements on biology and clinical impact of occulthepatitis b virus infection. J Hepatol 71:371–397

    Google Scholar 

  48. Squadrito G, Cacciola I, Alibrandi A, Pollicino T, Raimondo G (2013) Impact of occult hepatitis B virus infection on the outcome of chronic hepatitis C. J Hepatol 59:696–700

    PubMed  Google Scholar 

  49. Pollicino T, Saitta C (2014) Occult hepatitis B virus and hepatocellular carcinoma. World J Gastroenterol 20:5951–5961

    PubMed  PubMed Central  Google Scholar 

  50. Bensalem A et al (2016) Eastern region represents a worrying cluster of active hepatitis C in Algeria in 2012. J Med Virol 88(8):1394–1403

    PubMed  Google Scholar 

  51. Azzalini L, Ferrer E, Ramalho LN, Moreno M, Dominguez M, Colmenero J et al (2010) Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats. Hepatology 51:1567–1576

    CAS  PubMed  Google Scholar 

  52. Altamirano J, Bataller R (2010) Cigarette smoking and chronic liver diseases. Gut 59:1159–1162

    CAS  PubMed  Google Scholar 

  53. Can A, Dogan E, Bayoglu IV, Tatli AM, Besiroglu M, Kocer M et al (2014) Multicenter epidemiologic study on hepatocellular carcinoma in Turkey. Asian Pac J Cancer Prev 15:2923–2927

    PubMed  Google Scholar 

  54. Ohishi W, Fujiwara S, Cologne JB, Suzuki G, Akahoshi M, Nishi N et al (2008) Risk factors for hepatocellular carcinoma in a Japanese population: a nested case-control study. Cancer Epidemiol Biomarkers Prev 17:846–854

    CAS  PubMed  Google Scholar 

  55. Davila JA, Morgan RO, Shaib Y, McGlynn KA, El-Serag HB (2005) Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut 54:533–539

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Arora A, Kumar A (2014) Treatment response evaluation and follow-up in hepatocellular carcinoma. J Clin Exp Hepatol 4:S126–S129

    PubMed  PubMed Central  Google Scholar 

  57. Liu C, Xiao GQ, Yan LN, Li B, Jiang L, Wen TF et al (2013) Value of α-fetoprotein in association with clinic pathological features of hepatocellular carcinoma. World J Gastroenterol 19:1811–1819

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Qari YA, Mosli MH (2017) Epidemiology and clinical features of patients with hepatocellular carcinoma at a tertiary hospital in Jeddah. Niger J Clin Pract 20:43–47

    CAS  PubMed  Google Scholar 

  59. Saffroy R, Pham P, Reffas M, Takka M, Lemoine A, Debuire B (2007) New perspectives and strategy research biomarkers for hepatocellular carcinoma. Clin Chem Lab Med 45:1169–1179

    CAS  PubMed  Google Scholar 

  60. Giannini EG, Cucchetti A, Erroi V, Garuti F, Odaldi F, Trevisani F (2013) Surveillance for early diagnosis of hepatocellular carcinoma: how best to do it. World J Gastroenterol 19:8808–8821

    PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the “Tunisian Secretariat for Scientific Research and Technology SERST for the Tunisian part of the study (LR: Epidémiologie et diversité génétique des virus hépatiques et des entérovirus, Contract: LR11SP09)”.

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Authors and Affiliations

  1. Laboratory of Clinical Virology, Pasteur Institute of Tunis 13, Place Pasteur, Le Belvedere PB 74, 1002, Tunis, Tunisia

    Ines Dhifallah, Marwa Khedhiri, Anissa Chouikha, Walid Hammami, Amel Sadraoui, Henda Triki & Olfa Bahri

  2. Department of Gastroenterology B, La Rabta Hospital, Faculty of Medicine, University of Manar, Tunis, Tunisia

    Nadia Maamouri

  3. Department of Gastroenterology, Hospital of Tahar Maamouri, Faculty of Medicine, University of Manar, Tunis, Tunisia

    Mohamed Msaddek Azzouz

  4. Department of General Surgery, Hospital of Mongi Slim, La Marsa, Faculty of Medicine, University of Manar, Tunis, Tunisia

    Tahar Khalfallah

  5. Faculty of Sciences of Bizerte, University of Carthage, Tunis, Tunisia

    Ines Dhifallah

  6. Faculty of Sciences of Tunis, University of Manar, Tunis, Tunisia

    Marwa Khedhiri

  7. Laboratory of Medical Epidemiology, Pasteur Institute of Tunis, Tunis, Tunisia

    Ghassen Kharroubi

  8. Nuclear Organization and Oncogene Unit, INSERM U993, Pasteur Institue, Paris, France

    Pascal Pineau

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  1. Ines Dhifallah
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Dhifallah, I., Khedhiri, M., Chouikha, A. et al. Hepatitis viruses take advantage of traditional practices to increase the burden of hepatocellular carcinoma in Tunisia. Arch Virol 165, 33–42 (2020). https://doi.org/10.1007/s00705-019-04440-5

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