Hepatobiliary Complications in Children with Sickle Cell Disease: A Retrospective Review of Medical Records from 616 Patients

Abstract

Hepatobiliary complications in children with sickle cell disease (SCD) are rarely reported but can be life-threatening. We retrospectively assessed their prevalence in a cohort of 616 children followed in a French university-hospital SCD reference center. Eligibility criteria were the following: age <18 years, seen at least twice with an interval of more than 6 months from January 2008 to December 2017, with all genotypes of SCD. Patients with hepatobiliary complications were identified via the local data warehouse and medical files were thoroughly reviewed. At least one hepatobiliary complication was reported in 37% of the children. The most frequent was cholelithiasis, in 25% of cases, which led to systematic screening and elective cholecystectomy in the case of gallstones. Overall, 6% of the children experienced acute sickle cell hepatic crisis, sickle cell intra-hepatic cholestasis, or acute hepatic sequestration, with severity ranging from mild liver pain and increased jaundice to multiple organ failure and death. Emergency treatment was exchange transfusion, which led to normalization of liver tests in most cases. Five children had chronic cholangiopathy, associated with auto-immune hepatitis in two cases. One needed liver transplantation, having a good outcome but with many complications. Transfusion iron load and infectious hepatitis cases were mild. Hepatotoxicity of an iron chelator was suspected to contribute to abnormal liver test results in five patients. We propose recommendations to prevent, explore, and treat hepatobiliary complications in SCD children. We underline the need for emergency exchange transfusion when acute liver failure develops and warn against liver biopsy and transplantation in this condition.

Pharmacokinetics of Voxelotor in Patients With Renal and Hepatic Impairment

“…14 Liver dysfunction is estimated to have a prevalence of 10% in adults with SCD and is expected to increase in the older population. 15 In 2 open-label clinical studies, we evaluated the safety, tolerability, and PK of voxelotor in subjects with various degrees of renal or hepatic insufficiency. The studies used a single-dose design, as voxelotor demonstrated linear, dose-proportional PK in single-(dose range, 100-2800 mg) and multiple-dose (dose range: 300-900 mg) cohorts of healthy subjects.…”

Severe Variant of Sickle Cell Intrahepatic Cholestasis a Difficult Approach Diagnosis Clinical Presentation and Outcome in Adult Population in the Congo

“…Our cohort is then quite representative of Adults with sickle cell disease in Brazzaville. Iron overload is suggested to cause abnormal liver enzyme level [13]. It would have been interested to measure the plasma ferritin level to our patients.…”

Chronic organ injuries in children with sickle cell disease

“…8 Hepatobiliary complications are more rarely reported in children with SCD, most probably because they are not routinely screened for and are thus under-diagnosed. 94 The pathophysiology of these complications is mostly related to the sickling of red blood cells, resulting in sinusoidal obstruction and ischemia of hepatocytes, as well as ischemia of bile ducts leading to cholangiopathy. Hemolysis-related hyperbilirubinemia promotes biliary lithiasis.…”

“…95 A retrospective review of 616 SCD children followedup in a reference center for both SCD and hepatology found that 37% had presented at least one hepatobiliary complication. 94 Among chronic complications, gallstones were diagnosed in 25% of children, cholangiopathy in 0.8%, autoimmune hepatitis in 0.5%, transfusion iron overload in 3%, and iron chelator toxicity was suspected in 0.8%. Over half of the gallstones were discovered incidentally, although complications occurred in 42% of cases, mostly occurring as pain, as well as cholecystitis, cholangitis, and pancreatitis.…”

“…Among acute complications, the combined prevalence of acute sickle cell crisis, sickle cell intrahepatic cholestasis, and acute hepatic sequestration was approximately 6%. 94 Post-transfusion iron overload is usually asymptomatic in children but may have severe consequences in adults. 93…”