Abstract
Chronic hepatitis C (CHC) and iron overload are the main causes of liver disease in β-thalassemia major (βTM). There is limited data regarding the course of CHC in this population. All patients (n = 144) from the thalassemia centre of the University Hospital of Patras were evaluated (January 1981 to June 2012). Patients were classified into group A (n = 57), which consisted of patients with CHC, who either had received antiviral treatment (n = 49) or not (n = 8), and group B which included 87 patients without CHC. Nineteen patients died during follow-up (median: 257.5 months (1–355)). Survival rates were 84.2 % and 88.5 % for group A and B, respectively. The causes of death were heart failure (63.2 %), accident (10.5 %), sepsis (5.3 %), liver failure (5.3 %), hepatocellular carcinoma (HCC) (5.3 %), non-Hodgkin lymphoma (5.3 %) and multiorgan failure (5.3 %). There were no differences in total survival between the two groups (p = 0.524). In the multivariate analysis, survival was neither correlated with CHC (p = ns), nor with anti-HCV treatment (p = ns), whereas independent negative predictors were presence of heart failure (p < 0.001), presence of malignancy other than HCC (p = 0.001) and non-adherence to chelation treatment (p = 0.013). Predictive factors for the development of cirrhosis were: CHC (p < 0.001), age > 35 years (p = 0.007), siderosis grade 3/4 (p = 0.029) and splenectomy (p = 0.001); however, multivariately, only siderosis grade 3/4 was found to be significant (p = 0.049). In this study, survival of patients with βTM was mainly associated with heart failure, presence of malignancy other than HCC and non-adherence to chelation treatment, rather than with liver disease. Multicentre studies need to be designed to define more accurately the indications of antiviral treatment in this population.
Similar content being viewed by others
References
Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD, Del Vecchio GC, Romeo MA, Forni GL, Gamberini MR, Ghilardi R, Piga A, Cnaan A (2004) Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 89:1187–1193
Ladis V, Chouliaras G, Berdoukas V, Chatziliami A, Fragodimitri C, Karabatsos F, Youssef J, Kattamis A, Karagiorga-Lagana M (2011) Survival in a large cohort of Greek patients with transfusion-dependent beta thalassaemia and mortality ratios compared to the general population. Eur J Haematol 86:332–338
Charafeddine K, Isma’eel H, Charafeddine M, Inati A, Koussa S, Naja M, Taher A (2008) Survival and complications of beta-thalassemia in Lebanon: a decade's experience of centralized care. Acta Haematol 120:112–116
Zurlo MG, De Stefano P, Borgna-Pignatti C, Di Palma A, Piga A, Melevendi C, Di Gregorio F, Burattini MG, Terzoli S (1989) Survival and causes of death in thalassaemia major. Lancet 2(8653):27–30
Angelucci E, Pilo F (2008) Treatment of hepatitis C in patients with thalassemia. Haematologica 93(8):1121–1123
Prati D, Maggioni M, Milani S, Cerino M, Cianciulli P, Coggi G, Forni GL, Magnano C, Meo A, Gramignoli R, Rebulla P, Fiorelli G, Cappellini MD (2004) Cooleycare Cooperative Group. Clinical and histological characterization of liver disease in patients with transfusion-dependent β-thalassemia. A multicenter study of 117 cases. Haematologica 89:1179–1186
Perifanis V, Tziomalos K, Tsatra I, Karyda S, Patsiaoura K, Athanassiou-Metaxa M (2005) Prevalence and severity of liver disease in patients with β thalassemia major. A single-institution fifteen-year experience. Haematologica 90:1136–1138
Angelucci E (1994) Antibodies to hepatitis C virus in thalassemia. Haematologica 79:353–355
Di Marco V, Capra M, Angelucci E, Borgna-Pignatti C, Telfer P, Harmatz P, Kattamis A, Prossamariti L, Filosa A, Rund D, Gamberini MR, Cianciulli P, De Montalembert M, Gagliardotto F, Foster G, Grangè JD, Cassarà F, Iacono A, Cappellini MD, Brittenham GM, Prati D, Pietrangelo A, Craxì A, Maggio A, Italian Society for the Study of Thalassemia and Haemoglobinopathies, Italian Association for the Study of the Liver (2010) Management of chronic viral hepatitis in patients with thalassemia: recommendations from an international panel. Blood 116:2875–2883
Ragab L, Helal S, Zaghloul N, El-Raziky M, Afifi R, Musallam KM, Taher AT (2010) Clinicovirologic analysis of hepatitis C infection in transfusion-dependent β-thalassemia major children. Int J Lab Hematol 32:184–190
Chakravarti A, Verma V, Kumaria R, Dubei AP (2005) Anti-HCV seropositivity among multiple transfused patients with beta thalassaemia. J Indian Med Assoc 103(2):64–66
Di Marco V, Lo IO, Almasio P, Ciaccio C, Capra M, Rizzo M, Malizia R, Maggio A, Fabiano C, Barbaria F, Craxì A (1997) Long-term efficacy of alpha-interferon in beta-thalassemics with chronic hepatitis C. Blood 90(6):2207–2212
Alavian SM, Tabatabaei SV (2010) Treatment of chronic hepatitis C in polytransfused thalassaemic patients: a meta-analysis. J Viral Hepat 17(4):236–244
Harmatz P, Jonas MM, Kwiatkowski JL, Wright EC, Fischer R, Vichinsky E, Giardina PJ, Neufeld EJ, Porter J, Olivieri N, Thalassemia Clinical Research Network (2008) Safety and efficacy of pegylated interferon alpha-2a and ribavirin for the treatment of hepatitis C in patients with thalassemia. Haematologica 93(8):1247–1251
Mirmomen S, Daryani NE, Malekzadeh R et al (2004) The efficacy and safety of peginterferon alpha-2a (PEGASYS) in the treatment of chronic hepatitis C infected subjects with transfusion dependent thalassemia. Hepat Mon 4(7):65–70
Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C (2005) Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Ann N Y Acad Sci 1054:445–450
Cao A (2004) Quality of life and survival of patients with beta-thalassemia major. Haematologica 89(10):1157–1159
Li CK, Chan PK, Ling SC, Ha SY (2002) Interferon and ribavirin as frontline treatment for chronic hepatitis C infection in thalassaemia major. Br J Haematol 117(3):755–758
Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN et al (1995) Histological grading and staging of chronic hepatitis. J Hepatol 22(6):696–699
Brissot P, Bourel M, Herry D, Verger JP, Messner M, Beaumont C, Regnouard F, Ferrand B, Simon M (1981) Assessment of liver iron content in 271 patients: a re-evaluation of direct and indirect methods. Gastroenterology 80(3):557–565
Agarwal MB, Malkan GH, Bhave AA, Vishwanathan C, Billa V, Dube SR, Bajan K, Rajadhyaksha GC, Shah SH (1993) Antibody to hepatitis-C virus in multi-transfused thalassaemics—Indian experience. J Assoc Phys India 41(4):195–197
Ameli M, Besharati S, Nemati K, Zamani F (2008) Relationship between elevated liver enzyme with iron overload and viral hepatitis in thalassemia major patients in northern Iran. Saudi Med J 29(11):1611–1615
Resti M, Azzari C, Rossi ME, Vullo C, Zammarchi E, Vierucci A (1992) Hepatitis C virus antibodies in a long-term follow-up of beta-thalassaemic children with acute and chronic non-A non-B hepatitis. Eur J Pediatr 151(8):573–576
Lai M, De Virgilis S, Argiolu F, Farci P, Mazzoleni AP, Lisci V, Rapicetta M, Clemente MG, Nurchis P, Arnone M et al (1993) Evaluation of antibodies to hepatitis C virus in a long-term prospective study of posttransfusion hepatitis among thalassemic children: comparison between first- and second-generation assay. J Pediatr Gastroenterol Nutr 16(4):458–464
Chiaramonte M, Stroffolini T, Caporaso N, Coppola R, Craxì A, Gaeta GB, Sagnelli E, Zanetti AR (1991) Hepatitis-C virus infection in Italy: a multicentric sero-epidemiological study (a report from the HCV study group of the Italian Association for the Study of the Liver). Ital J Gastroenterol 23(9):555–558
Maggio A, Di Marzo R, Giambona A, Renda M, Acuto S, Lo Gioco P, D'Alcamo E, Di Trapani F, Marino M, Abate I et al (1990) Beta-thalassemia mutations in Sicily. Ann N Y Acad Sci 612:67–73
Erer B, Angelucci E, Lucarelli G, Giardini C, Baronciani D, Galimberti M, Polchi P, Amadei G, Battistini L, Paolucci S et al (1994) Hepatitis C virus infection in thalassemia patients undergoing allogeneic bone marrow transplantation. Bone Marrow Transplant 14(3):369–372
Sievert W, Pianko S, Warner S, Bowden S, Simpson I, Bowden D, Locarnini S (2002) Hepatic iron overload does not prevent a sustained virological response to interferon-alpha therapy: a long term follow-up study in hepatitis C-infected patients with beta thalassemia major. Am J Gastroenterol 97(4):982–987
Angelucci E, Muretto P, Nicolucci A, Baronciani D, Erer B, Gaziev J, Ripalti M, Sodani P, Tomassoni S, Visani G, Lucarelli G (2002) Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation. Blood 100(1):17–21
Labropoulou-Karatza C, Goritsas C, Fragopanagou H, Matsouka P, Spiliopoulou II, Barbatis C (2000) Adult beta-thalassemic patients with chronic hepatitis C: long-term efficacy of alpha-IFN treatment. Eur J Intern Med 11(3):161–164
Artan R, Akcam M, Yilmaz A, Kocacik D (2005) Interferon alpha monotherapy for chronic hepatitis C viral infection in thalassemics and hemodialysis patients. J Chemother 17(6):651–655
Spiliopoulou I, Repanti M, Katinakis S, Karana-Ginopoulou A, Papanastasiou DA (1999) Response to interferon alfa-2b therapy in mutitransfused children with beta-thalassemia and chronic hepatitis C. Eur J Clin Microbiol Infect Dis 18(10):709–715
Tinè F, Magrin S, Craxì A, Pagliaro L (1991) Interferon for non-A, non-B chronic hepatitis. A meta-analysis of randomised clinical trials. J Hepatol 13(2):192–199
Telfer PT, Garson JA, Whitby K, Grant PR, Yardumian A, Hoffbrand AV, Wonke B (1997) Combination therapy with interferon alpha and ribavirin for chronic hepatitis C virus infection in thalassaemic patients. Br J Haematol 98(4):850–855
Saffar MJ, Saffar H, Khlilian AR, Naqshvar F (2009) Combination therapy with interferon and ribavirin for chronic hepatitis C infection in beta-thalassaemia major. East Mediterr Health J 15(4):785–791
Inati A, Taher A, Ghorra S, Koussa S, Taha M, Aoun E, Sharara AI (2005) Efficacy and tolerability of peginterferon alpha-2a with or without ribavirin in thalassaemia major patients with chronic hepatitis C virus infection. Br J Haematol 130(4):644–646
Clemente MG, Congia M, Lai ME, Lilliu F, Lampis R, Frau F, Frau MR, Faa G, Diana G, Dessì C et al (1994) Effect of iron overload on the response to recombinant interferon-alfa treatment in transfusion-dependent patients with thalassemia major and chronic hepatitis C. J Pediatr 125:123–128
Di Marco V, Lo IO, Capra M, Grutta S, Ciaccio C, Gerardi C, Maggio A, Renda D, Almasio P, Pisa R et al (1992) Alpha-Interferon treatment of chronic hepatitis C in young patients with homozygous beta-thalassemia. Haematologica 77(6):502–506
Donohue SM, Wonke B, Hoffbrand AV, Reittie J, Ganeshaguru K, Scheuer PJ, Brown D, Dusheiko G (1993) Alpha interferon in the treatment of chronic hepatitis C infection in thalassaemia major. Br J Haematol 83(3):491–497
Syriopoulou V, Daikos GL, Kostaridou SL, Manolaki N, Nakopoulou L, Kattamis A, Kattamis C (2005) Sustained response to interferon alpha-2a in thalassemic patients with chronic hepatitis C. A prospective 8-year follow-up study. Haematologica 90(1):129–131
Ancel D, Amiot X, Chaslin-Ferbus D, Hagege I, Garioud A, Girot R, Pol S, Grange JD (2009) Treatment of chronic hepatitis C in sickle cell disease and thalassaemic patients with interferon and ribavirin. Eur J Gastroenterol Hepatol 21(7):726–729
Di Marco V, Capra M, Gagliardotto F, Borsellino Z, Cabibi D, Barbaria F, Ferraro D, Cuccia L, Ruffo GB, Bronte F, Di Stefano R, Almasio PL, Craxì A (2008) Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C. Haematologica 93(8):1243–1246
Deugnier Y, Turlin B, Ropert M, Cappellini MD, Porter JB, Giannone V, Zhang Y, Griffel L, Brissot P (2011) Improvement in liver pathology of patients with β-thalassemia treated with deferasirox for at least 3 years. Gastroenterology 141(4):1202–1211
Poli G (2000) Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med 21:49–98
Mancuso A, Sciarrino E, Renda MC, Maggio A (2006) A prospective study of hepatocellular carcinoma incidence in thalassemia. Hemoglobin 30(1):119–124
Borgna-Pignatti C, Vergine C, Lombardo T, Cappellini MD, Cianciulli P, Maggio A, Renda D, Lai ME, Mandas A, Forni G, Piga A, Bisconte MG (2004) Hepatocellular carcinoma in the thalassaemia syndromes. Br J Haematol 124(1):114–117
Poynard T, Bedossa P, Opolon P (1997) Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 349:825–832
Vogt M, Lang T, Frosner G, Klingler C, Sendl AF, Zeller A, Wiebecke B, Langer B, Meisner H, Hess J (1999) Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening. N Engl J Med 341:866–870
Lange CM, Zeusem S (2011) IL28B single nucleotide polymorphisms in the treatment of hepatitis C. J Hepatol 55(3):692–701
Lin CY, Chen JY, Lin TN et al (2011) IL28B SNP rs 12979860 is a clinical predictor for on-treatment and sustained virologic response in patients with hepatitis C virus genotype 1 infection. PLoS One 6(3):e18322
Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401
Di Marco V, Bronte F, Calvaruso V, Capra M, Capra M, Borsellino Z, Maggio A, Renda MC, Pitrolo L, Lo Pinto MC, Rizzo M, Fiorenza F, Gerardi C, Grimaudo S, Di Cristina A, Levrero M, Craxì A (2012) IL28B polymorphisms influence stage of the liver fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection. Haematologica 97(5):679–686
Conflict of interest
None declared.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Triantos, C., Kourakli, A., Kalafateli, M. et al. Hepatitis C in patients with β-thalassemia major. A single-centre experience. Ann Hematol 92, 739–746 (2013). https://doi.org/10.1007/s00277-013-1692-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-013-1692-6