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.

Keywords: acute hepatic crisis; cholangiopathy; cholelithiasis; sickle cell hepatopathy.

Figure 1

Pathophysiology of hepatobiliary complications in sickle cell disease (SCD). Sinusoidal obstruction by sickled red blood cells results in hepatocyte ischemia, with secondary ballooning of adjacent hepatocytes and intracanalicular cholestasis. Vascular obstruction may also cause red cell and platelet trapping in the liver, leading to acute hepatic sequestration. Depending on the relative degrees of ischemia, cholestasis, and cell trapping, the crises may present as acute sickle cell hepatic crisis, sickle cell intra-hepatic cholestasis, or hepatic sequestration. Bile ducts ischemia secondary to sickling is responsible for cholangiopathy, and chronic hemolysis is responsible for hyperbilirubinemia, promoting cholelithiasis formation.

Figure 2

Prevalence of hepatobiliary complications in 616 children with sickle cell disease, followed up in our reference center from January 2008 to December 2017. “Acute hepatic crisis” includes acute sickle cell hepatic crisis and sickle cell intrahepatic cholestasis.

Figure 3

Screening for acute hepatobiliary complications. ALT: alanine aminotransferase; ERCP: endoscopic retrograde cholangiopancreatography; γ-GT: gamma-glutamyltransferase.

Figure 4

Screening for chronic hepatobiliary complications. ALT: alanine aminotransferase; ANCAs: antineutrophil cytoplasmic antibodies; ERCP: endoscopic retrograde cholangiopancreatography; MDR3: multidrug resistance protein 3; γ-GT: gamma-glutamyltransferase.