Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis
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 natur...
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Published in | Liver transplantation Vol. 22; no. 9; pp. 1245 - 1253 |
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Main Authors | , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
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01.09.2016
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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 |
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AbstractList | 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. 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 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 |
Author | Ling, Simon C. Jones, Nicola Cutz, Ernest Angelis, Maria Naqvi, Ahmed Cattral, Mark Nalli, Nadya Fecteau, Annie Kamath, Binita Ghanekar, Anand Amir, Achiya Z. Ng, Vicky Grant, David Avitzur, Yaron Weitzman, Sheila |
Author_xml | – sequence: 1 givenname: Achiya Z. surname: Amir fullname: Amir, Achiya Z. organization: Hepatology and Nutrition, University of Toronto – sequence: 2 givenname: Simon C. surname: Ling fullname: Ling, Simon C. organization: Hepatology and Nutrition, University of Toronto – sequence: 3 givenname: Ahmed surname: Naqvi fullname: Naqvi, Ahmed organization: University of Toronto – sequence: 4 givenname: Sheila surname: Weitzman fullname: Weitzman, Sheila organization: University of Toronto – sequence: 5 givenname: Annie surname: Fecteau fullname: Fecteau, Annie organization: University of Toronto – sequence: 6 givenname: David surname: Grant fullname: Grant, David organization: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto – sequence: 7 givenname: Anand surname: Ghanekar fullname: Ghanekar, Anand organization: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto – sequence: 8 givenname: Mark surname: Cattral fullname: Cattral, Mark organization: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto – sequence: 9 givenname: Nadya surname: Nalli fullname: Nalli, Nadya organization: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto – sequence: 10 givenname: Ernest surname: Cutz fullname: Cutz, Ernest organization: University of Toronto – sequence: 11 givenname: Binita surname: Kamath fullname: Kamath, Binita organization: Hepatology and Nutrition, University of Toronto – sequence: 12 givenname: Nicola surname: Jones fullname: Jones, Nicola organization: Hepatology and Nutrition, University of Toronto – sequence: 13 givenname: Maria surname: Angelis fullname: Angelis, Maria organization: Transplant and Regenerative Medicine Centre, The Hospital for Sick Children, University of Toronto – sequence: 14 givenname: Vicky surname: Ng fullname: Ng, Vicky organization: Hepatology and Nutrition, University of Toronto – sequence: 15 givenname: Yaron surname: Avitzur fullname: Avitzur, Yaron organization: Hepatology and Nutrition, University of Toronto |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27216884$$D View this record in MEDLINE/PubMed |
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SubjectTerms | Adolescent Biopsy Child Child, Preschool Cross-Sectional Studies Disease Progression Female Ferritins - blood Fibrinogen - analysis Graft Rejection - prevention & control Humans Immunosuppression - methods Immunosuppressive Agents - therapeutic use Infant Liver Liver - pathology Liver Failure, Acute - blood Liver Failure, Acute - etiology Liver Failure, Acute - mortality Liver Failure, Acute - surgery Liver Transplantation Lymphohistiocytosis, Hemophagocytic - complications Lymphohistiocytosis, Hemophagocytic - diagnosis Lymphohistiocytosis, Hemophagocytic - mortality Male Rare Diseases - complications Recurrence Retrospective Studies Survival Rate Time-to-Treatment Treatment Outcome Triglycerides - blood |
Title | Liver transplantation for children with acute liver failure associated with secondary hemophagocytic lymphohistiocytosis |
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