Successful liver transplantation for acute sickle cell intrahepatic cholestasis: A case report and review of the literature

Table 1 Summary of unique manifestations of sickle cell hepatopahty

SCD manifestation	Pathophyiology of the disease	Histopathology	Clinical presentation	Amino-transferases	ALP	Bilirubin	Management
Acute sickle cell hepatic crises	Sickled RBCs obstruct liver sinusoids causing ischemic infarction	- Presence of sickle cell aggregates in the liver sinusoids	Fever, abdominal pain, jaundice and tender hepatomegaly	Elevated up to 3 fold the upper limit of normal followed by rapid resolution	Normal to slighly elevated	Conjugated hyperbilirubinemia up to 15 mg/dL, usually normalizes within 2 weeks	Supportive; hydration, oxygenation, pain control and blood exchange as needed
		- Kupffer cell hypertrophy and centrilobular necrosis
Acute hepatic sequestration	Kupffer cell erythrophagocytosis traps sickled RBCs resulting in blood pooling within liver sinusoids	- Presence of dilated blood-filled liver sinusoids	Sudden severe RUQ pain and rapidly worsening anemia with appropriate reticulocytosis; severe cases can present with shock and hepatomegaly	Normal	Elevated; up to 650 U/L	Conjugated hyperbilirubinemia up to 24 mg/dL	Cautious blood transfuison or exchange transfusion; excessive transfusion can result in rapid rise of Hb during resolution phase precipitating stroke and heart failure
Acute intrahepatic cholestasis	Diffuse sickling in liver sinusoids leading to widespread ischemia as well as Kupffer cell hypertrophy and extramedullary hematopoiesis which contribute to cholestasis	- Presence of massively dilated blood sinusoids with clusters of sickled RBCs	Fever, RUQ pain, acute liver failure and multi-system organ failure	Elevated; typically > 1000 U/L	Normal or elevated up to >1000 U/L	Conjugated hyperbilirubinemia up to > 30 mg/dL	Supportive with exchange transfusion and LT
		- Presence of intracanalicular and intraductal cholestasis
		- Ballooning of hepatocytes, necrosis, inflammation
Sickle cell cholangiopathy	Incomplete occlusion of the peribiliary vascular plexus results in hypoxia and dilatation of the bile ducts; recurrent insults can result in ischemic stricture	- Presence of ischemic necrosis and fibrosis of the bile ducts	Jaundice and biliary stone compications, imaging can reveal non-obstructive bile duct dilatation and/or obstructive biliary strictures	Normal or elevated	Elevated	Elevated	ERCP stenting and balloon dilatation, LT

SCD: Sickle cell disease; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; RBC: Red blood cell; RUQ: Right upper quadrant; Hb: Hemoglobin; LT: Liver transplant; ERCP; Endoscopic retrograde cholangiopancreatography.

Table 2 Reports of patients with intrahepatic sickle cell cholestasis who underwent liver transplantation

Ref.	Year	Number of cases	Age of the patient	Outcomes
Emre et al[15]	2000	1	6	First transplant was complicated by graft failure from veno-occlusive disease, required re-LT.
				Second transplant was complicated by graft failure from hepatic artery thrombosis, required re-LT.
				The patient died 6 mo after third LT from sepsis.
Ross et al[18]	2002	1	49	The patient died 22 mo after LT due to pulmonary embolism.
Gilli et al[19]	2002	1	22	The patient was alive 3 mo after LT.
Baichi et al[7]	2005	1	27	Post-LT course was complicated by sepsis, multiorgan failure, perihepatic hematoma and hemorrhagic ascites; the patient died 35 d after LT.
Mekeel et al[9]	2007	2	8,17	Patients were followed up over a mean period of 4.2 yr.
				Patient 1 was alive at end of follow-up with mild recurrent HCV.
				Patient 2 had recurrent sickle cell hepatopathy post-transplant and died of cerebral complications 6 yr following LT.
Hurtova et al[6]	2011	5	32-47	Patient 1 died of recurrent HCV-induced decompensated cirrhosis and sepsis 11 yr after LT.
				Patient 2 had recurrent HCV with moderate fibrosis; died of ischemic cholangitis and sepsis after 4 yr after LT.
				Patient 3 had recurrent HCV infection. He was alive 8 yr after LT.
				Patient 4's post-operative course was complicated by posterior leukoencephalopathy; the patient died from sepsis 16 mo after LT.
				Patient 5 developed biliary strictures requiring stenting. The patient was alive 42 mo after LT.
Blinder et al[20]	2013	1	37	Immediate post-LT course was complicated with seizure and respiratory failure. The patient had no post-operative SCD-related complications in the 12 mo after transplant and was maintained on hydroxyurea without need for exchange transfusion.
Lui et al[3]	2018	1	29	The patient was alive 7 mo after LT with no reported complications.

LT: Liver transplant; HCV: Hepatitis C virus; SCD: Sickle cell disease.