Management of Liver Complications in Haemoglobinopathies

Pierre Brissot,Olivier Loreal

doi:10.4081/thal.2014.4869

Abstract

Liver complications in haemoglobinopathies (thalassaemia and sickle cell disease) are due to several factors, dominated (beside chronic viral infections, not considered here) by chronic iron overload, biliary obstruction and venous thrombosis. Whereas the latter two factors can cause acute hepatic syndromes, all three mechanisms - when becoming chronic- can produce fibrosis and cirrhosis and even, in thalassaemia, hepatocellular carcinoma. These chronic hepatic complications are an indirect consequence of the significant improvement in life expectancy due to the overall amelioration of disease management. The diagnostic approach has benefited from non invasive (biochemical and imaging) approaches which have considerably reduced the indication of liver biopsy. The therapeutic management involves relatively efficient curative medical, endoscopic or surgical methods, but should rest primarily on preventive measures focused on the haematological causative factors but also on hepatic co-morbidities. This chapter will focus on hepatic complications in thalassaemia and sickle cell disease (SCD), without considering the complications related to virus B or C infections which will be described in another chapter.

Highlights

This chapter will focus on hepatic complications in thau lassaemia and sickle cell disease (SCD), without considering the complil cations related to virus B or C infections which will be described in anothia er chapter. erc Background m Harmful factors for the liver om Factors related to haematological disease c Iron overload - In thalassaemia:[1] Repeated transfusions represent the major cause n of iron overload in thalassemia major(TM)
This will lead to the appearance of plasma non-transferrin bound iron (NTBI),[2] an iron species which has the property to be very rapidly taken up by parenchymal cells, accounting primarily for hepatic iron overload, the liver being, for circulating iron, both the first line target and the main storage organ
Dyserythropoiesis is the primary iron overloading factor in non-transfusion dependent thalassemia,[5,6] where iron pathophysiology is very close to that of hepcidin deficient

Summary

Ineffective erythropoiesis is much less involved in SCD as compared

Whereas erythrocyte degradation takes place predominantly in the bone marrow in TH, leading to ineffective erythropoiesis, it occurs primarily within the vascular system in SCD.[9] Another difference with TM is the inflammatory state often present in SCD. Reported.[27] It may be related to tissue iron excess and to intravascular hemolysis through heme-induced endothelial toxicity.[9] On the long-term, the risk is that of fibrosis and cirrhosis.[9,13]. Biliary obstruction In thalassaemia: A multicenter study in 858 TM patients concluded to a remarkable prevalence (30%) of cholelithiasis.[12,13] Increased bilirubin production, related to chronic hemolysis, is the primary cause, but the presence of a Gilbert syndrome genotype (resulting in the decreased production of conjugated bilirubin) favors[14] both the fre-

Biliary obstruction

Vascular obstruction

Functional data

Severe liver failure will benefit from general intensive care

Findings

Imaging techniques