Transplantation for liver failure in patients with sickle cell disease: Challenging but feasible

Abstract

Sickle cell disease (SCD) frequently affects the liver; if acute liver failure (ALF) develops, the only potentially effective therapeutic option is liver transplantation (LT). Only 12 patients for whom LT was performed for SCD-related ALF have been described so far. We report a retrospective series of 6 adult patients with SCD (3 men and 3 women, median age ¼ 40.1 years) who underwent emergency LT. The indication for LT was ALF complicating cirrhosis in 5 patients (hepatitis C/iron overload-induced cirrhosis in 3 and iron overload-induced cirrhosis in 2); one patient had autoimmune hepatitis. The median follow-up was 52.7 months (0.5-123 months). The 1-, 3-, 5-, and 10-year survival rates were 83.3%, 66.7%, 44.4%, and 44.4%, respectively. One patient died of hepatocellular failure precipitated by hyperacute allograft rejection on post-LT day 10. Soon after LT, 2 patients developed seizures; in 1 case, the seizures were a complication of early calcineurin inhibitor-induced leukoencephalopathy. Four long-term survivors benefited from specific management of SCD; specifically, the hemoglobin S fraction was maintained below 30% and the total hemoglobin level was maintained between 8 and 10 g/dL. Two patients had mild vaso-occlusive crises. Three patients experienced a recurrence of hepatitis C virus (HCV) infection; 2 of these patients experienced reversible neurological complications while they were receiving antiviral treatment. Carefully selected patients with SCD may benefit from emergency LT. However, such patients seem to be particularly susceptible to neurological complications after LT. In contrast, severe SCD-related crises do not seem to recur if specific management is provided. Outcomes may be improved if the neurological complications can be minimized; for example, the administration of a calcineurin inhibitor can be delayed, and the management of HCV infection recurrence can be improved. Liver Transpl 17:381-392, 2011. V C 2011 AASLD.Received September 7, 2010; accepted December 20, 2010.Sickle cell disease (SCD) is one of the most common autosomal recessive disorders. It affects newborn infants at a rate of 1/2065 in France 1 and approximately 100,000 individuals in the United States. SCD is characterized by the presence of hemoglobin S (HbS). The polymerization of this abnormal hemoglobin (Hb) on exposure to low oxygen tension leads to abnormal rheology and vaso-occlusion. Chronic hemolytic anemia, periodic and painful vaso-occlusive crises (VOCs) affecting bones, infections secondary to asplenia, and eventually multiorgan failure are the most prominent features of SCD.Virtually all organs can be affected by vaso-occlusion.3-5 The liver is frequently involved, and different patterns of hepatic injury associated with different prognoses have been described. [6][7][8][9][10]

How we treat sickle hepatopathy and liver transplantation in adults

“…1,17,18,[27][28][29][30][31][32][33][34][35][36][37] However, several questions remain unanswered. The poor results reported in early case series have improved, to some degree, in later studies.…”

Uncommon Hepatic Sequelae from an Acute Sickle Cell Crisis

“…7 However, transplantation experience is very limited. Only 18 transplant cases have been reported in the literature.…”

“…Only 18 transplant cases have been reported in the literature. 7 Hepatic vascular re-thrombosis and associated phenomenon (i.e. neurovascular injury) from post-operative sickle cell crises add to the inherent morbidity/mortality risk.…”

“…neurovascular injury) from post-operative sickle cell crises add to the inherent morbidity/mortality risk. 7 Consequently, the overall mortality rate in SCD patients with acute hepatic failure undergoing transplant is 60%. 6 Optimization of post-operative management will improve as transplantation is considered early in patients where fatal hepatic failure is anticipated.…”

Toward dual hematopoietic stem-cell transplantation and solid-organ transplantation for sickle-cell disease

“…22 Notably, liver disease is likely multifactorial from viral hepatitis, iron overload, and ischemic injury. 23 Manci et al 24 reported that 74.7% of the patients had evidence 1 (50) 89 (78-96) 8 (62) 93 (89-96) 1 y 92 (87)(88)(89)(90)(91)(92)(93)(94)(95)(96) 4 (66) 89 (78)(79)(80)(81)(82)(83)(84)(85)(86)(87)(88)(89)(90)(91)(92)(93)(94)(95)(96) 1 (50) 76 (62-88) 8 (62) 87 (83-91) 2 y 87 (80)(81)(82)(83)(84)(85)(86)(87)(88)(89)…”