Evaluation of Liver Disease in a Cohort of Patients Affected by Thalassemia Intermedia.
Authors: Motta Irene , Rumi Maria Grazia , Cesaretti Claudia , Aghemo Alessio , Fraquelli Mirella , Roghi Alberto , Cappellini Maria Domenica 
Published: October 2019

Abstract
Abstract 4064
Poster Board III-999

Introduction
Liver disease is the second cause of death for thalassemia major (TM) patients, mainly due to HCV infection and transfusional iron overload. Few data are so far available for thalassemia intermedia (TI) patients who are much less transfused but, because of chronic anemia they have an increased iron absorption.

Aim
the aim of this study was to evaluate the prevalence of liver disease and its progression in adult non-transfusion dependent TI patients.

Patients and Methods
Seventy adult TI patients (32 female/38 male, aged 42±14 years, range 22-77) regularly cared at Hereditary Anemia Center, University of Milan, were enrolled in this study in 1997 and followed for 10±1 years. Seven patients were lost and 4 died during follow-up. At enrolment (T0) 50 were splenectomized, 51 were occasionally transfused, 46 were irregularly chelated. Twenty-four (34,2%) patients were anti HCV positive of whom 13 (54,1%) were RNA positive.

Results
Liver transaminases were significantly different (p=0.001) among HCV-RNA positive and negative patients (ALT 59,7±32,1 vs 26,9±20,3 U/L; AST 49,1±22,8 vs 30,6±17,0 U/L respectively). Ferritin levels in the overall group were significantly higher than normal values (734±748 ng/ml). No significant difference in ferritin levels was detected among HCV-RNA positive and negative patients, while overall a correlation (r=0.687, p<0.001) between ferritin and ALT was observed. Among HCV-RNA negative patients regularly followed (49), at enrolment 12 (24,4%) had abnormal transaminases. During the follow up 12/37 (32,4%) who had normal transaminases at T0 showed abnormal values, and evaluating the overall HCV-RNA negative group abnormal transaminases were noticed in 24/49 (48,9%). Ferritin levels were increased also at the final observation (T1), but not as much as supposed to be considering the annual increased iron absorption. At T1Transient Elastography (TE), for evaluating liver fibrosis, and MRI T2*, for measuring liver iron, became available thus 42 patients had these evaluations: 9/42 had TE values >7.9 kPa (corresponding to fibrosis stage F≥2 of Metavir), and the mean value was 6,7±6,2 kPa; almost all the patients (39/42 – 92,8%) had significant high level of liver iron concentration (LIC measured through MRI T2*≥2 mg/g d.w.) with a correlation between LIC T2* and Fibroscan values (r=0.489, p=0.003). During the follow up 4 patients died: 1 for stroke and 3/4 for liver disease,(one Hepatocarcinoma (HCC) in HCV-RNA positive patient and 2 decompensated cirrhosis). Other two cases of HCC were observed, one in a patient HCV-RNA positive and 1 in an HCV-RNA negative patient; the latter having significant iron overload (LIC through MRI T2* 23,29 mg/g/dw) and a Fibroscan value diagnostic for cirrhosis (43,5 kPa).

Conclusions
Liver disease is the first cause of death in TI patients; 3 cases of HCC were observed in patient aged 49±1 years old of whom 1 without hepatitis viral infection. The liver damage, detected with high levels of ALT and AST in both HCV-RNA positive and negative patients is mainly related to the parenchymal iron overload and HCV infection. Ferritin, commonly used to monitor iron overload, properly reflects the degree of iron concentration in TM, while is inadequate in TI patients because, even though it correlates with LIC, it underestimates the iron overload. Actually in TI patients iron coming from duodenal absorption is mainly stored in parenchymal liver tissue, while in TM it's primarily distributed in the reticulo-endothelial system that stimulate ferritin production. In conclusion it's mandatory the use of other methods to evaluate LIC, such as MRI T2*, and the introduction of regular chelation therapy in the management of TI patients.

Disclosures:
No relevant conflicts of interest to declare.