CHARACTERISTICS AND PROGNOSIS OF HEPATOCELLULAR CARCINOMA IN MULTI-TRANSFUSED PATIENTS WITH THALASSEMIA MAJOR. EXPERIENCE OF A SINGLE TERTIARY CENTER.

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Nikolaos Papadopoulos *
Dimitrios Kountouras
Katerina Malagari
Maria Tampaki
Maria Theochari
John Koskinas
(*) Corresponding Author:
Nikolaos Papadopoulos | nipapmed@gmail.com

Abstract

Background: In this retrospective study, records of patients with thalassemia major (TM) diagnosed with hepatocellular carcinoma (HCC) from 2008‐2018 were reviewed in order to determine the survival rate and evaluate possible etiological factors associated with survival.


Methods: Forty-two TM patients who were diagnosed with HCC have been included in the study. Most of our patients (78.5%) were anti-HCV positive, while 16.5% had evidence of resolved HBV infection. At the time of HCC diagnosis, 78.5% of our patients were diagnosed with cirrhosis, while the vast majority (98%) had normal or mild elevated liver iron concentration (LIC) values. According to Barcelona Clinic Liver Cancer (BCLC) grading system patients were classified as 0-A: 28.5%, B: 57% and as C-D: 14.5%.  HCC has been treated with loco-regional treatment in 78.5% of our patients, while the rest have been treated with sorafenib.


Results: Twenty-eight patients (66.5%) have eventually died with a median survival time of 6 months (range: 2-60). Using the Cox proportional hazard model, the only factors who have been associated with poor survival were BCLC stages C and D.


Conclusions: In conclusion, BCLC staging is the main prognostic factor of survival in patients with TM who develop HCC, with a median survival time of six months.


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References

1. Moukhadder HM, Halawi R, Cappellini MD, Taher AT. Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: a comprehensive review. Cancer 2017;123:751–758.
2. Borgna-Pignatti C, Garani MC, Forni GL, Cappellini MD, Cassinerio E, Fidone C, Spadola V, Maggio A, Restivo Pantalone G, Piga A, Longo F, Gamberini MR, Ricchi P, Costantini S, D'Ascola D, Cianciulli P, Lai ME, Carta MP, Ciancio A, Cavalli P, Putti MC, Barella S, Amendola G, Campisi S, Capra M, Caruso V, Colletta G, Volpato S. Hepatocellular carcinoma in thalassaemia: an update of the Italian Registry. Br J Haematol. 2014;167:121-126.
3. Prati D, Zanella A, Farma E, De Mattei C, Bosoni P, Zappa M, Picone A, Mozzi F, Rebulla P, Cappellini MD, Allain JP, Sirchia G. A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous b-thalassemia. Blood. 1998;92:3460-3464.
4. Mancuso A, Rigano P, Renda D, Di Salvo V, Pignatti CB, Guddo F, Buccellato A, Nicoli N, Maggio A. Hepatocellular carcinoma on cirrhosis-free liver in a HCV-infected thalassemic. Am J Hematol 2005;78:158-159.
5. Minola E, Prati D, Suter F, Maggiolo F, Caprioli F, Sonzogni A, Fraquelli M, Paggi S, Conte D. Age at infection affects the longterm outcome of transfusion-associated chronic hepatitis C. Blood 2002;99:4588-4591.
6. Papatheodoridis G, Dalekos G, Sypsa V, Yurdaydin C, Buti M, Goulis J, Calleja JL, Chi H, Manolakopoulos S, Mangia G, Gatselis N, Keskin O, Savvidou S, de la Revilla J, Hansen BE, Vlachogiannakos I, Galanis K, Idilman R, Colombo M, Esteban R, Janssen HL, Lampertico P. PAGE-B predicts the risk of developing hepatocellular carcinoma in Caucasians with chronic hepatitis B on 5-year antiviral therapy. J Hepatol 2016;64:800-806.
7. Kew MC. Hepatic iron overload and hepatocellular carcinoma. Cancer Lett. 2009;286:38-43.
8. Gandon Y, Olivié D, Guyader D. Non-invasive assessment of hepatic iron stores by MRI. Lancet 2004;363:357–362.
9. Hankins JS, McCarville MB, Loeffler RB, Smeltzer MP, Onciu M, Hoffer FA, Li CS, Wang WC, Ware RE, Hillenbrand CM. R2* magnetic resonance imaging of the liver in patients with iron overload. Blood 2009;113:4853-4855.
10. Bertuccio P, Turati F, Carioli G, Rodriguez T, La Vecchia C, Malvezzi M, Negri E. Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol 2017;67:302–309.
11. Restivo Pantalone G, Renda D, Valenza F, D'Amato F, Vitrano A, Cassarà F, Rigano P, Di Salvo V, Giangreco A, Bevacqua E, Maggio A. Hepatocellular carcinoma in patients with thalassaemia syndromes: clinical characteristics and outcome in a long term single centre experience. Br J Haematol. 2010;150:245-247.
12. Balogh J, Victor D, Asham EH, Burroughs SG, Boktour M, Saharia A, Li X, Ghobrial RM, Monsour HP Jr. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma 2016;3:41-53.
13. Sekine S, Ito K, Watanabe H, Nakano T, Moriya K, Shintani Y, Fujie H, Tsutsumi T, Miyoshi H, Fujinaga H, Shinzawa S, Koike K, Horie T. Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein. ToxicolApplPharmacol. 2015;282:237-243.
14. 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. Survival and complications in patients with thalassemia major treated with transfusion and deferoxamine. Haematologica 2004;89:1187-1193.
15. Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med 2013;158:329–337.
16. Mancuso A. Hepatocellular carcinoma in thalassemia: A critical review. World J Hepatol 2010;2:171-174.
17. EASL Recommendations on Treatment of Hepatitis C 2018. J Hepatol 2018;69:461-511.
18. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. European Association for the Study of the Liver. J Hepatol 2018;69:182-236.
19. Cabibbo G, Enea M, Attanasio M, Bruix J, Craxi A, Camma C. A meta-analysis of survival rates of untreated patients in randomized clinical trials of hepatocellular carcinoma. Hepatology 2010;51:1274–1283.
20. Staikou C, Stavroulakis E, Karmaniolou I. A narrative review of peri-operative management of patients with thalassaemia. Anaesthesia 2014;69:494-510.
21. Forner A, Reig ME, de Lope CR, Bruix J. Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis 2010;30:61–74.
22. Llovet JM, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J-F, de Oliveira AC, Santoro A, Raoul JL, Forner A, Schwartz M, Porta C, Zeuzem S, Bolondi L, Greten TF, Galle PR, Seitz JF, Borbath I, Häussinger D, Giannaris T, Shan M, Moscovici M, Voliotis D, Bruix J; SHARP Investigators Study Group. Sorafenib in advanced hepatocellular carcinoma. N Engl J Med 2008;359:378–390.
23. Llovet JM, Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003;37:429–442.
24. Burrel M, Reig M, Forner A, Barrufet M, de Lope CR, Tremosini S, Ayuso C, Llovet JM, Real MI, Bruix J . Survival of patients with hepatocellular carcinoma treated by transarterialchemoembolisation (TACE) using Drug Eluting Beads. Implications for clinical practice and trial design. J Hepatol 2012;56:1330–1335.