Orthotropic Liver Transplantation for Acute Intrahepatic Cholestasis in Sickle Cell Disease: Clinical and Histopathologic Features of a Rare Case

Abstract

Sickle cell disease has a wide range of hepatic manifestations, with acute intrahepatic cholestasis being one of the rarest and most fatal, often resulting in acute fulminant hepatic failure. Liver transplantation is an emerging but rarely utilized treatment for hepatic failure in the setting of sickle cell disease. Few such cases have been reported in the literature, with little emphasis on histopathologic correlation. We report a case of acute intrahepatic cholestasis in a patient with sickle cell disease who underwent orthotropic liver transplantation and describe novel correlating histopathologic features. The patient is a 29-year-old man who presented with hyperbilirubinemia, acute kidney injury, and coagulopathy. He was diagnosed clinically with acute intrahepatic cholestasis and received an orthotropic liver transplant. The explanted liver demonstrated marked sinusoidal expansion by sickled erythrocytes, hyperplastic Kupffer cells, and extramedullary hematopoiesis. There was extensive sinusoidal and centrizonal fibrosis with occlusion of central veins reminiscent of chronic sinusoidal obstructive syndrome, a previously undescribed pattern of injury. This case represents one of the few reported cases of sickle cell intrahepatic cholestasis treated by transplantation and demonstrates the rarely reported histopathologic features and gives insight to a potentially new mechanism of injury in these patients. Familiarity with the morphologic features of sickle cell hepatopathy and its clinical manifestations is important as transplantation in sickle cell-related liver injury increases in frequency.

Liver transplantation in patients with sickle cell disease: possible but challenging—a cohort study

“…In practice, LT can be indicated in two settings [4]: acute liver failure mimicking fulminant hepatitis and end‐stage chronic liver disease. Data regarding liver transplantation (LT) in patients with SCD are limited to mostly case reports (Table 1) [5‐24]. Because of the paucity of data available regarding the indications for LT and perioperative outcomes as well as the lack of long‐term follow‐up in most reported cases, the present study entailed a thorough analysis of a large single‐center experience of LT in patients with SCD.…”

Sickle Cell Intrahepatic Cholestasis: Extremely Rare but Fatal Complication of Sickle Cell Disease

“…Management is directed to not only treat the worsening liver function but also manage the end-organ damage accompanied by it. Patients with sickle cell intrahepatic cholestasis show evidence of associated coagulopathy and worsening kidney function [ 14 - 16 ].…”

Acute Liver Failure in Sickle Cell Disease: A Perfect Storm

“…While multiple comorbidities and coagulopathy prevented liver biopsy, acute sickle cell hepatopathy may be a contraindication in itself [ 17 ]. In end-stage liver disease, transplantation may be considered in the context of the patient’s clinical status although this intervention is associated with high mortality and is not yet proven to be effective [ 18 - 20 ].…”