title: Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis.
abstract: Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening systemic disease, characterized by overwhelming stimulation of the immune system and categorized as primary or secondary types. Occasionally, acute liver failure (ALF) may dominate the clinical presentation. Given the systemic nature of HLH and risk of recurrence, HLH is considered by many a contraindication to liver transplantation (LT). The aim of this study is to review our single-center experience with LT in children with secondary HLH and ALF (HLH-ALF). This is a cross-sectional, retrospective study of children with secondary HLH-ALF that underwent LT in 2005-2014. Of 246 LTs, 9 patients (3 males; median age, 5 years; range, 0.7-15.4 years) underwent LT for secondary HLH-ALF. Disease progression was rapid with median 14 days (range, 6-27 days) between first symptoms and LT. Low fibrinogen/high triglycerides, elevated ferritin, hemophagocytosis on liver biopsy, and soluble interleukin 2 receptor levels were the most commonly fulfilled diagnostic criteria; HLH genetic studies were negative in all patients. Immunosuppressive therapy after LT included corticosteroids adjusted to HLH treatment protocol and tacrolimus. Thymoglobulin (n = 5), etoposide (n = 4), and alemtuzumab (n = 2) were used in cases of recurrence. Five (56%) patients experienced HLH recurrence, 1 requiring repeat LT, and 3 died. Overall graft and patient survival were 60% and 67%, respectively. Six patients are alive and well at a median of 24 months (range, 15-72 months) after transplantation. In conclusion, LT can be beneficial in selected patients with secondary HLH-ALF and can restore good health in an otherwise lethal condition. Liver Transplantation 22 1245-1253 2016 AASLD.
authors.affiliation: Division of Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.|Paediatric Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Achiya Z
authors.initials: AZ
authors.lastname: Amir
authors.affiliation: Paediatric Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Ling
authors.affiliation: Haematology and Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Naqvi
authors.affiliation: Haematology and Oncology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sheila
authors.initials: S
authors.lastname: Weitzman
authors.affiliation: General Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Annie
authors.initials: A
authors.lastname: Fecteau
authors.affiliation: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Grant
authors.affiliation: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anand
authors.initials: A
authors.lastname: Ghanekar
authors.affiliation: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Cattral
authors.affiliation: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nadya
authors.initials: N
authors.lastname: Nalli
authors.affiliation: Pathology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ernest
authors.initials: E
authors.lastname: Cutz
authors.affiliation: Paediatric Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Binita
authors.initials: B
authors.lastname: Kamath
authors.affiliation: Paediatric Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nicola
authors.initials: N
authors.lastname: Jones
authors.affiliation: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Maria
authors.initials: M
authors.lastname: De Angelis
authors.affiliation: Paediatric Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Vicky
authors.initials: V
authors.lastname: Ng
authors.affiliation: Paediatric Gastroenterology, Hepatology and Nutrition, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Yaron
authors.initials: Y
authors.lastname: Avitzur
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005293:Ferritins / Q000097:blood; D005340:Fibrinogen / Q000032:analysis; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D008099:Liver / Q000473:pathology; D017114:Liver Failure, Acute / Q000097:blood / Q000209:etiology / Q000401:mortality / Q000601:surgery*; D016031:Liver Transplantation; D051359:Lymphohistiocytosis, Hemophagocytic / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D035583:Rare Diseases / Q000150:complications*; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate; D061665:Time-to-Treatment; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D007166:Immunosuppressive Agents; D014280:Triglycerides; D005340:Fibrinogen; D005293:Ferritins