Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic disease characterized by overwhelming stimulation of the immune system. Occasionally, acute liver failure (ALF) may dominate the clinical presentation resulting in brisk and fatal deterioration. Given the systemic nature of HLH and risk of recurrence, HLH-associated ALF is considered by many a contraindication to liver transplantation (LTx). Herein, we describe our experience and outcomes of LTx in children with secondary HLH-associated ALF.
Methods: A cross-sectional retrospective study of children diagnosed with ALF associated with secondary HLH that underwent LTx between 2005 and 2014. HLH was diagnosed according to the HLH-2004 guidelines.
Results: Of a total 246 LTx, 9 patients (3 males; median age 5 years, range 0.7-15.4) were transplanted for HLH-associated ALF. Disease progression was rapid with median 14 (range 6-27) days between first symptoms to LTx. Hemophagocytosis on liver biopsy, low fibrinogen/high triglycerides, elevated ferritin and soluble-IL2-receptor levels were the most sensitive criteria for diagnosis and were positive in 100%, 89%, 89% and 88% of patients respectively. Genetic studies were negative in all patients. All patients received post-transplantation tacrolimus and high dose corticosteroids. Thymoglobulin (n=5), etoposide (n=4) and alemtuzumab (n=2) were used for recurrent (n=5) or resistant disease (n=2). 5 patients (56%) had HLH recurrence, one requiring repeat LTx. Overall graft and patient survival were 60% and 67% respectively.
Conclusion: Secondary HLH-associated ALF poses a diagnostic and therapeutic challenge. LTx can be beneficial in selected patients with secondary HLH-associated ALF and can restore good health in an otherwise lethal condition.
