Hepatocellular carcinoma as an emerging morbidity in the thalassemia syndromes: A comprehensive review

• Published in: Cancer Vol. 123; no. 5; pp. 751 - 758
• Main Authors: Moukhadder, Hassan M., Halawi, Racha, Cappellini, Maria Domenica, Taher, Ali T.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-03-2017
• Subjects: Attenuation; Cancer; Carcinogenesis; Carcinogenesis - genetics; Carcinogenicity; Carcinogens; Carcinoma, Hepatocellular - complications; Carcinoma, Hepatocellular - diagnostic imaging; Carcinoma, Hepatocellular - physiopathology; Chelation; Chronic infection; Damage; Disorders; Genotoxicity; Hepacivirus - pathogenicity; Hepatitis; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic - diagnostic imaging; Hepatitis B, Chronic - pathology; Hepatitis B, Chronic - virology; Hepatitis C; Hepatitis C virus; Hepatitis C, Chronic - diagnostic imaging; Hepatitis C, Chronic - pathology; Hepatitis C, Chronic - virology; Hepatocellular carcinoma; Humans; Immunosurveillance; Incidence; Iron; iron overload; Iron Overload - diagnostic imaging; Iron Overload - physiopathology; Liver; Liver cancer; Liver Neoplasms - complications; Liver Neoplasms - diagnostic imaging; Liver Neoplasms - physiopathology; Liver transplantation; Magnetic induction; Magnetic resonance imaging; Morbidity; Oncology; Patients; Prevention; Resonance; Risk analysis; Risk Factors; Screening; Surgery; Thalassemia; Thalassemia - complications; Thalassemia - physiopathology; Thalassemia - virology; Transplantation; Ultrasound; Vaccination; Viruses; hepatitis C virus; iron overload; thalassemia; hepatitis B virus; hepatocellular carcinoma
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.30462

The incidence of hepatocellular carcinoma (HCC) in patients with thalassemia is on the rise. The 2 well recognized HCC risk factors in thalassemia are iron overload and chronic viral infection with hepatitis C. The carcinogenicity of iron is related to its induction of oxidative damage, which results in genotoxicity, and to immunologic dysregulation, which attenuates cancer immune surveillance. Chronic hepatitis B and C infections lead to necroinflammation, which can prompt progression to HCC, but an independent role of hepatitis B virus in hepatic carcinogenesis among patients with thalassemia has not been demonstrated. Screening patients who have thalassemia using magnetic resonance imaging‐based liver iron concentration measurement and liver ultrasound is recommended for early detection of iron overload and HCC, respectively. Prevention primarily resides in hepatitis B vaccination, donor blood screening, hepatitis treatment, and iron chelation. Although solid data is lacking on the outcomes of HCC treatment in patients with thalassemia, a personalized approach tailored to the individual patient's comorbidities remains necessary for treatment success. Treatment modalities for HCC include surgical resection, chemoembolization, and liver transplantation, among others. Multicenter studies are needed to better explore therapeutic targets that can improve the prognosis of these patients. Cancer 2017;123:751–58. © 2016 American Cancer Society.
Hepatocellular carcinoma is an emerging morbidity in thalassemia. No guidelines have been established on the treatment of hepatocellular carcinoma in patients with thalassemia, but there is compelling evidence that systematic screening and prevention programs, in conjunction with appropriate iron chelation and viral hepatitis treatment, constitute the mainstay of management of this entity in thalassemia patients.