Vincenzo De Sanctis1, Ashraf T. Soliman2, Shahina Daar3, Niveen Alansary4, Antonis Kattamis5, Myrto Skafida5, Maria Concetta Galati6, Soteroula Christou7, Saveria Campisi8, Giuseppe Messina9, Mohamed A. Yassin10, Duran Canatan11, Salvatore Di Maio12, Soad Al Jaouni13, Giuseppe Raiola14, Mehran Karimi15, Valeria Kaleva16, Shruti Kakkar17, Demetris Mariannis18 and Christos Kattamis19.
1 Pediatric and Adolescent Outpatient Clinic, Quisisana Hospital, Ferrara, Italy.
2 Department of Pediatrics, Division of Endocrinology, Hamad General Hospital, Doha, Qatar.
3 Department of Haemtology, College of Medicine & Health Sciences Sultan Qaboos University, Muscat, Oman & Stellenbosch Institute for Advanced Study (STIAS), Wallenberg Research Centre at Stellenbosch University, Stellenbosch, South Africa.
4 Department of Haematology, Sultan Qaboos University Hospital, Sultanate of Oman.
5 Thalassemia Unit, Division of Pediatric Hematology-Oncology. First Department of Pediatrics, University of Athens, “Agia Sofia” Children's Hospital, Athens, Greece.
6 Department of Pediatric Haematoncology, Thalassaemia and Prenatal Diagnosis Regional Center, Pugliese-Ciaccio Hospital, Catanzaro, Italy.
7 Archbishop Makarios III, Thalassemia Center, Nicosia, Cyprus.
8 U.O.S.D. Thalassemia, Umberto 1° Hospital, Siracusa, Italy.
9 SSD Centro per le Microcitemie- Azienda Grande Ospedale Metropolitano, Reggio Calabria,Italy.
10 National Center for Cancer Care and Research, Medical Oncology Hematology Section HMC, Doha, Qatar.
11 Director of Thalassemia Diagnosis Center of Mediterranean Blood Diseases Foundation, Antalya, Turkey.
12 Emeritus Director in Pediatrics, Children’s Hospital “Santobono-Pausilipon”, Naples, Italy.
13 Hematology Department, King Abdulaziz University Hospital, Faculty of Medicine
King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
14 Department of Paediatrics, Pugliese-Ciaccio Hospital,Catanzaro, Italy.
15 Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
16 Center for Coagulopathies and Rare Anemias,Varna, Bulgaria.
17 Department of Pediatrics, Dayanand Medical College & Hospital, Ludhiana, India.
18 Royal Lancaster Infirmary, United Kingdom.
19 First Department of Pediatrics, Aghia Sophia Children Hospital, National Kapodistrian University of Athens, Athens, Greece.
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to the recent alarming increase in the incidence of hepatocellular
carcinoma (HCC) in thalassemias, the present report reviews briefly the
frequency, the major risk factors, and the surveillance of HCC in
β-thalassemias. Over the past 33 years, 153 cases of HCC were reported
in patients with thalassemia, mainly in Italy and Greece. Among
HCV-infected patients, additional factors promoting the development of
HCC included: advanced age, male sex, chronic hepatitis B (CHB)
co-infection, and iron overload. For early diagnosis of HCC, sequential
ultrasound screening is recommended especially for thalassemia patients
with chronic hepatitis C (CHC), which coincides with (one or more)
additional risk factors for HCC. Here we report also the preliminary
data from thalassemic patients, above the age of 30 years, followed in
13 ICET-A centers. The total number of enrolled patients was 1,327
(males: 624 and 703 females). The prevalence of HCC in thalassemia
major patients [characterized by transfusion-dependency (TDT)] and
thalassemia intermedia [characterized by nontransfusion dependency
(NTDT)] was 1.66 % and 1.96 % , respectively. The lowest age at
diagnosis of HCC was 36 years for TDT and 47 years for NTDT patients.
We hope that this review can be used to develop more refined and
prospective analyses of HCC magnitude and risk in patients with
thalassemia and to define specific international guidelines to support
clinicians for early diagnosis and treatment of HCC in thalassemic
Frequency of HCC in the General Population and in Thalassemias
The ICET-A Experience
|Table 1. Demographic details of TDT and NTDT patients with hepatocellular carcinoma (HCC), above the age of 30 years, in 13 thalassemia centers from 10 different countries.|
|Table 2. Summary of clinical, laboratory and diagnostic data in thalassemic patients with hepatocellular carcinoma (HCC) in Italy.|
|Table 3. Summary of clinical, laboratory and diagnostic data in thalassemic patients with hepatocellular carcinoma (HCC) in Italy, Oman and Greece.|
|Table 4. Summary of clinical, laboratory and diagnostic data in thalassemic patients with hepatocellular carcinoma (HCC) in Cyprus.|
Major Risk Factors in Thalassemic Patients with HCC
Pathophysiology Past and Recent Issues
|Figure 1. Risk factors for HCC in thalassemias (From: Sciancalepore et al. J Cancer Ther. 2018; 9:417-437; modified).|
|Figure 2. Flow chart of HCC surveillance in thalassemias in countries with prolonged implementation of HCV screening of donors.|