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

Abstract

Sickle cell intrahepatic cholestasis (SCIC) is a rare but potentially fatal complication of sickle cell disease (SCD), with high mortality, observed mainly in patients with homozygous sickle cell anemia. Herein, we have reported a case of severe SCIC with a poor outcome despite aggressive measures including exchange transfusion and use of vasopressors.The patient was admitted with generalized weakness, confusion, rigors, chills, and signs of hepatic failure, such as hyperbilirubinemia, hypoalbuminemia, and coagulopathy. There was no evidence of viral hepatitis or biliary obstruction. The patient received two exchange transfusions, but he continued to deteriorate clinically despite exchange transfusion and developed hemorrhagic shock and multiorgan failure. The patient was made comfort care as per family wishes. This case emphasizes the importance of early diagnosis of sickle cell intrahepatic cholestasis and poor prognosis despite aggressive measures.

Acute Liver Failure With Liver Enzymes >5,000 in Sickle Cell Disease

“…1 Of note, there is conflicting data on optimal post-transfusion HbS goal, with some suggesting ,30 mg/DL and others ,20 mg/DL. 4,13 In our patient, HbS was noted to be 39 mg/DL immediately after one session of RBCEx and 35 mg/DL 2 days later. Given his rapid clinical improvement, the decision was made not to pursue additional exchange to decrease HbS to a predetermined goal.…”

“…However, transplantation poses unique perioperative and postoperative risks with mortality rates that remain high. 4,7 In our patient, simple transfusion was attempted first with no clinical response. After RBCEx, hepatic function rapidly improved within 24 hours, consistent with the literature suggesting initial improvement occurring within 48 hours, with complete return to baseline within 6 days.…”

“…2 Hepatic involvement in SCD is a rare and potentially fatal complication, seen primarily among those with homozygous sickle cell mutations. 1,3,4 Cases of hepatic involvement in SCD have been sparsely documented in the literature, mostly described in children and with limited follow-up. 1,5 The pathophysiology of sickle cell intrahepatic cholestasis (SCIC) involves sickling of sinusoidal hemoglobin within the liver, leading to intracanalicular obstruction, extensive hepatocyte necrosis, and dysfunction driven by cell hypoxia.…”

Principais manifestações hepáticas na doença falciforme

“…Além disso, em biópsias também foram observadas dilatação sinusoidal e eritrofagocitose pelas células de Kupffer. (Khan et al, 2022;Shah et al, 2017) Em casos mais graves, pode ocorrer necrose generalizada dos hepatócitos. (Khan et al, 2022;Praharaj & Anand, 2021;Shah et al, 2017) Laboratorialmente, a colestase intra-hepática apresenta-se com transaminases elevadas, podendo atingir valores superiores a 1.000 UI/L e hiperbilirrubinemia acentuada, que pode ser decorrente da combinação de três variáveis: (1) hemólise, (2) colestase e (3) lesão renal aguda.…”

“…(Khan et al, 2022;Shah et al, 2017) Em casos mais graves, pode ocorrer necrose generalizada dos hepatócitos. (Khan et al, 2022;Praharaj & Anand, 2021;Shah et al, 2017) Laboratorialmente, a colestase intra-hepática apresenta-se com transaminases elevadas, podendo atingir valores superiores a 1.000 UI/L e hiperbilirrubinemia acentuada, que pode ser decorrente da combinação de três variáveis: (1) hemólise, (2) colestase e (3) lesão renal aguda. Bilirrubina conjugada e não conjugada secundária à hemólise contribuem para hiperbilirrubinemia profunda, com a fração conjugada geralmente sendo superior a não conjugada.…”