LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY

With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important c...

Full description

Saved in:
Bibliographic Details
Main Authors: Ashraf Tawfik Soliman, Mohamed Yassin, Fawzia AlYafei, Lolwa Al-Naimi, Noora Almarri, Aml Sabt, Vincenzo De Sanctis
Format: Article
Language:English
Published: PAGEPress Publications 2014-04-01
Series:Mediterranean Journal of Hematology and Infectious Diseases
Subjects:
Online Access:http://www.mjhid.org/index.php/mjhid/article/view/1385
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846143898574913536
author Ashraf Tawfik Soliman
Mohamed Yassin
Fawzia AlYafei
Lolwa Al-Naimi
Noora Almarri
Aml Sabt
Vincenzo De Sanctis
author_facet Ashraf Tawfik Soliman
Mohamed Yassin
Fawzia AlYafei
Lolwa Al-Naimi
Noora Almarri
Aml Sabt
Vincenzo De Sanctis
author_sort Ashraf Tawfik Soliman
collection DOAJ
description With regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox (Exjade- DFX ), an  oral single dose therapy has improved the compliance to chelation therapy. Aims: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX therapy in relation to ferritin level and IGF-I level. Methods: Liver function tests including: serum bilirubin, alanine transferase (ALT), aspartate transferase (AST) , albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every 6 months in 40 patients with BTM, with hepatitis negative screening (checked every year), for at  least   five years of DFO therapy and 4-5 years of DFX therapy . Results: DFX  therapy (20 mg/kg/day)  significantly decreased serum ferritin level in patients with BTM, this was associated with significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum  ferritin concentrations ( r = 0.45 and 0.33 respectively , p < 0.05) . IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that impairment of hepatic function negatively affects IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.
format Article
id doaj-art-d7a8e6cecdb6400abe05f6b3f5a103b1
institution Kabale University
issn 2035-3006
language English
publishDate 2014-04-01
publisher PAGEPress Publications
record_format Article
series Mediterranean Journal of Hematology and Infectious Diseases
spelling doaj-art-d7a8e6cecdb6400abe05f6b3f5a103b12024-12-02T09:47:06ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062014-04-0161e2014025e201402510.4084/mjhid.2014.0251145LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPYAshraf Tawfik Soliman0Mohamed YassinFawzia AlYafeiLolwa Al-NaimiNoora AlmarriAml SabtVincenzo De SanctisDivision of Pediatric Endocrinology Hamad Medical Center Doha QatarWith regular blood transfusion and iron chelation therapy, most patients with thalassemia major (BTM) now survive beyond the third decade of life . Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are important causes of liver pathology. Iron chelation with desferrioxamine (Desferal)  reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox (Exjade- DFX ), an  oral single dose therapy has improved the compliance to chelation therapy. Aims: To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX therapy in relation to ferritin level and IGF-I level. Methods: Liver function tests including: serum bilirubin, alanine transferase (ALT), aspartate transferase (AST) , albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every 6 months in 40 patients with BTM, with hepatitis negative screening (checked every year), for at  least   five years of DFO therapy and 4-5 years of DFX therapy . Results: DFX  therapy (20 mg/kg/day)  significantly decreased serum ferritin level in patients with BTM, this was associated with significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum  ferritin concentrations ( r = 0.45 and 0.33 respectively , p < 0.05) . IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that impairment of hepatic function negatively affects IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. Conclusions: Some impairment of liver function can occur in hepatitis negative BMT patients with iron overload. The use of DFX was associated with mild but significant reduction of ALT, AST and ALP and increase in IGF-I levels. The negative correlation between IGF-I and ALT concentrations suggest that preventing hepatic dysfunction may improve the growth potential in these patients.http://www.mjhid.org/index.php/mjhid/article/view/1385Thalassemia, liver enzymes, Insulin-like growth factor-I (IGF-I), chelation therapy
spellingShingle Ashraf Tawfik Soliman
Mohamed Yassin
Fawzia AlYafei
Lolwa Al-Naimi
Noora Almarri
Aml Sabt
Vincenzo De Sanctis
LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY
Mediterranean Journal of Hematology and Infectious Diseases
Thalassemia, liver enzymes, Insulin-like growth factor-I (IGF-I), chelation therapy
title LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY
title_full LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY
title_fullStr LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY
title_full_unstemmed LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY
title_short LONGITUDINAL STUDY ON LIVER FUNCTIONS IN PATIENTS WITH THALASSEMIA MAJOR BEFORE AND AFTER DEFERASIROX (DFX) THERAPY
title_sort longitudinal study on liver functions in patients with thalassemia major before and after deferasirox dfx therapy
topic Thalassemia, liver enzymes, Insulin-like growth factor-I (IGF-I), chelation therapy
url http://www.mjhid.org/index.php/mjhid/article/view/1385
work_keys_str_mv AT ashraftawfiksoliman longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy
AT mohamedyassin longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy
AT fawziaalyafei longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy
AT lolwaalnaimi longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy
AT nooraalmarri longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy
AT amlsabt longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy
AT vincenzodesanctis longitudinalstudyonliverfunctionsinpatientswiththalassemiamajorbeforeandafterdeferasiroxdfxtherapy