Clinical management of sickle cell liver disease in children and young adults

Abstract

Liver involvement in sickle cell disease (SCD) is often referred to as sickle cell hepatopathy (SCH) and is a complication of SCD which may be associated with significant mortality. This review is based on a round-table workshop between paediatric and adult hepatologists and haematologists and review of the literature. The discussion was prompted by the lack of substantial data and guidance in managing these sometimes very challenging cases. This review provides a structured approach for the diagnosis and management of SCH in children and young adults. The term SCH describes any hepatobiliary dysfunction in the context of SCD. Diagnosis and management of biliary complications, acute hepatic crisis, acute hepatic sequestration and other manifestations of SCH are discussed, as well as the role of liver transplantation and haemopoietic stem cell transplantation in the management of SCH.

Keywords: adolescent health; gastroenterology; jaundice.

Figure 1. Pathophysiology of sickle cell hepatopathy

The polymerization of deoxygenated HbS is the origin of all the complications of SCD. It increases the rigidity of the red cell with consequent damage to the vascular endothelium and vaso-occlusion, resulting in a cascade of pathological processes, including infarction, haemolysis, inflammation, hypercoagulability and oxidative stress. HbS: haemoglobin S Permission has been obtained from the illustrator Dr Vassiliki Tzomaka to include the above illustration in the figure of this article.

Figure 2. Sickling in end arteries of bile ducts

The diagram on the left illustrates the sickling in the end arteries perfusing the bile ducts. The picture on the right is an MRCP of a child with sickle cholangiopathy showing intrahepatic cholangiopathy with dilatations and strictures but no dominant stricture. MRCP: magnetic resonance cholangiopancreatography

Figure 3. Biopsy changes in sickle cell hepatopathy

Liver biopsy from an 11-year-old showing sinusoidal dilatation (long arrow) and porto-portal bridging fibrosis (short arrows). Sickle cells are visible within the sinusoids in this biopsy from a 12-year-old (B, main image). In acute hepatic sequestration, large numbers of sickled cells can be seen within congested sinusoids (B, lower inset). Iron overload can be seen within cells of the reticuloendothelial system (upper inset) and hepatocytes (long arrow). A liver biopsy from a 17-year-old demonstrating features of autoimmune liver disease in the form of a porto-lobular hepatitis with plasma cell rich interface activity (C, main image). The same child demonstrated cholangiopathic features in the form of concentric periductal fibrosis (C, lower inset) and periductal lymphoplasmacytic inflammation around portal areas (C, upper inset). Cholangiopathic features in the form of duct loss attributed to ischaemic damage demonstrated in panel D. Duct destruction was a prominent feature of this biopsy from a 7-year-old with sickle cell disease and autoimmune liver disease. The upper inset demonstrates a destructive cholangitis affecting interlobular calibre bile ducts (D, upper inset, H&E x200 magnification) and the lower inset demonstrates plasma cell rich inflammation surrounding septal calibre bile ducts (D, lower inset).