Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes.

National registries constitute an invaluable source of information and contribute to the improvement of hemoglobinopathy management. Herein, we present the second updated report of the National Registry for Haemoglobinopathies in Greece (NRHG) and critically discuss the time trends in demographics, affected births, and causes of mortality. Thirty-eight Greek hemoglobinopathy units reported data from diagnosis to the last follow-up or death by retrospectively completing an electronic form. Four thousand thirty-two patients were eligible for inclusion; more than half of them had thalassaemia major. Compared to the previous report, a reduction in the total number of all hemoglobinopathies except for hemoglobinopathy "Η" was evident. The total number of affected births was also reduced; most of them were attributable to diagnostic errors and lack of awareness. Importantly, data on iron overload are reported for the first time; although most patients had low or moderate liver iron concentration (LIC) values, a non-negligible proportion of patients had high LIC. The burden due to heart iron overload was less prominent. Cardiac- and liver-related complications are the major causes of morbidity and mortality. From 2000 to 2015, a decrease in heart-related deaths along with an increase in liver-associated fatalities was observed. The Hellenic Prevention Program along with advances in chelation regimens and iron status monitoring have resulted in improved patient outcomes. The NRHG gives insight into the effectiveness of prevention programs, the therapeutic management of hemoglobinopathies and associated outcomes. NRHG may contribute to the formulation of a roadmap for hemoglobinopathies in Europe and promote the implementation of effective public health policies.

Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with β-thalasaemia major (β-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with β-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir-ritonavir + dasabuvir ± RBV. Sixty-one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug-drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with β-TM and advanced liver disease was highly effective and safe.

Background: Effective iron chelation and other supportive treatment have a substantial impact on survival prolongation of thalassemic patients, who may reach late adulthood, and therefore, may manifest various neoplastic disorders. However, no systemic analysis of the prevalence of neoplastic disorders in this patient population has been performed. Aims: We systematically analyzed all cases of malignant neoplastic disorders, occurred in a large cohort of Greek thalassemic patients and investigated for possible underlying predisposing factors. Patients and methods: Data of 3652 patients with hemoglobinopathies (Group I: beta-thalassemia homozygous N=1981, Group II: thalassemia Intermedia N=746, Group III: sickle-cell disease +/- beta-Thalassemia n=751, Group IV: hemoglobinopathy-H N=174) were retrieved, followed up at 24 specific Hospital Units, between 1985 and 2018. Totally, 165 cases of a malignant disorder were identified (overall prevalence 4.52%). The significance of the following predisposing factors was investigated: familial history of neoplasia, occupational exposure to known mutagens, previous autoimmunity, previous splenectomy, tobacco smoking, alcohol use, HBV, HCV or HIV infection, iron overload, hydroxyurea treatment, previous irradiation for extramedullary hematopoietic tumors and systemic use of androgens/estrogens. Results: Patients were 84 males and 81 females with a median age at diagnosis of the neoplastic disorder of 45 years (range 9-73 years). Higher prevalence of neoplasia was noted among patients of Groups I and II (4.99% vs 3.03% among patients of Groups III and IV, p<0.05). Table 1 shows histological diagnosis of the 165 neoplastic disorders, of which 139 (84.2%) were solid tumors and 26 (15.8%) hematological malignancies. The dominant malignancy was hepatocellular carcinoma, diagnosed in 63 patients, followed by thyroid cancer (17 cases), non-Hodgkin's lymphoma (13 cases), and renal cell carcinoma (10 cases). There was a strong positive association between hepatitis C virus infection and hepatocellular carcinoma, and a negative one between HCV infection and thyroid and renal cancer. Active HCV infection was found in 81 patients (49.1%) compared to an estimated prevalence of about 25% among the whole thalassemic patient population. Hepatocellular carcinoma was more frequently diagnosed in men (M/F ratio 1.86) of the fourth and fifth decade (median age 45 years) with thalassemia homozygous or intermedia (89% of the cases), with long-standing, untreated HCV infection (76%), irrespective of the burden of hepatic iron load, estimated with MRI T2*. Indeed, no difference in the occurrence of hepatocellular carcinoma, as well as of any other type of cancer was found, in relation to Liver Iron Concentration (LIC). Moreover, no preponderance of any HCV genotype was identified, but interestingly, all 1b HCV genotype-associated neoplasms were hepatocellular carcinoma (7 cases). Finally, no association between any of the remaining potential risk factors with the manifestation of any specific neoplastic disorder was observed. Discussion: In our large thalassemic patient cohort, representative of the whole country of Greece, we have identified increased prevalence of four types of cancer. Besides hepatocellular carcinoma, we have unexpectedly encountered high prevalence of thyroid and renal cancer, as well as of all types of lymphomas. These primary findings deserve further investigation, since, excluding hepatocellular carcinoma, no prominent or speculative causality can be currently attributed for the remaining malignancies. Disclosures Kattamis: Vifor Pharma: Consultancy; ApoPharma: Honoraria; CELGENE: Consultancy, Honoraria; Novartis: Consultancy, Honoraria.

Full-field ERG and mfERG are more sensitive tools for detecting early retinal changes in β-thalassemia patients compared with ophthalmoscopy, VEP, FAF imaging and OCT scans.