Annals of Hematology | 2021
Hepatocellular carcinoma in patients with thalassemia in the post-DAA era: not a disappearing entity
Abstract
Dear Editor, Hepatocellular carcinoma (HCC) is an emerging and growing entity among patients with thalassemia. In fact, both transfusion-dependent thalassemia (TDT) and nontransfusion-dependent thalassemia (NTDT) patients have well-recognized risk factor for developing HCC. Liver iron overload with concomitant liver fibrosis is clearly implicated in the development of HCC. Furthermore, many patients with thalassemia, particularly those who were born before the 1990s, have been infected with hepatitis C virus (HCV) [1]. Although also hepatitis B virus (HBV) plays a role in hepatocarcinogenesis [2], chronic infection with C virus remains one of the most prevalent and well-recognized risk factors for developing HCC. Diabetes and liver steatosis are emerging and previously less well identified causes of HCC increase with close interplay with previous ones [3]. As a consequence, in recent years, many efforts have been devoted to achieve iron overload reduction and HCV clearance with the purpose to reduce morbidity and slow HCC incidence. Since 1999, at our center, all patients who had detectable HCV-RNA in serum underwent available regimens of antiviral treatments. These treatments encompassed the use of Interferon (IFN) alone (from 1999 to 2010) or PEG-IFN plus ribavirin (from 2011 to 2013) which resulted in limited HCV clearance and severe toxicity and/or increase in red blood cell consumption [4]; recently from 2017 to 2018, almost all our patients were treated with new direct antiviral agent (DAA) and, consequently, are now in sustained virological response (SVR) [5]. The update of the Italian registry which collected HCC cases between December 2002 and December 2012 reported 60 new cases among patients with thalassemia (mean age at diagnosis, 48 years) [6]; five out of these 60 cases belonged to the UOSD Malattie Rare del Globulo Rosso of Cardarelli Hospital (Naples, Italy) which currently treats about 340 thalassemic patients (190 with TDT and 150 with NTDT, HCC local cumulative incidence 1.47 %). Herein we describe the new HCC cases diagnosed since January 2013 among our patients; all cases were incidentally diagnosed without any symptoms, based only on the semestral abdominal ultrasound (US) surveillance permanently active at our center; computerized tomography and/or magnetic resonance imaging were used to confirm diagnosis. Until December 2020, we detected eight cases of HCC: five cases in TDT (three males, two female), two cases in NTDT (one male, one female), and one case in a female patient who had undergone hematopoietic stem cells transplantation (HSCT) in 1997 (HCC cumulative incidence 3.36%). The mean age was 54 years (54.25 women, 54.5 men). One patient (n.1) developed two HCC lesions; the second was a recurrence in another liver site following 2 years from thermoablation (Table 1). All patients were HBsAg negative and, at time of HCC detection, all but one (n.8) were also HCV-RNA negative (data not shown). As shown in Table 1, two patients (n.1 and n.2) had been successfully treated with IFN plus ribavirin before 2015 and the other two (n.3 and n.5) had SVR following DAA treatment in 2016. One patient (n.8) affected by renal cancer [7] could not be treated with DAA because he was under cabozantinib treatment and developed a multifocal HCC at diagnosis. Only two patients (n.4 and n.7) had significantly elevated alpha-fetoprotein (AFP) levels at diagnosis and (n.6 and n.8) presented with multifocal disease. Two patients (25%) had diabetes (n.2 and n.7). HCC developed in three patients in absence of previous HCV infection: one TDT patient (n.4) was both HCV-RNA and anti-HCV antibodies negative but had an advanced stage cirrhosis for auto-immune * Paolo Ricchi [email protected]