title: Veno-occlusive disease of the liver in the absence of elevation in bilirubin in pediatric patients after hematopoietic stem cell transplantation.
abstract: Veno-occlusive disease (VOD) of the liver is a well-described and significant complication of hematopoietic stem cell transplantation (HSCT), with limited successful therapeutic options in severe cases. Prompt diagnosis and initiation of treatment is crucial to restrict the extent of disease. However, a subset of patients may not meet all current diagnostic criteria at presentation, and waiting for these to be met may delay therapy. We retrospectively reviewed 794 HSCT patients treated at our institution between 2003 and 2013, identifying 17 (2.1%) who developed VOD. Of these, 5 (29%) were noted to have an absence of elevated bilirubin at the time of VOD diagnosis and reversal of portal venous flow on ultrasound. Median total and conjugated bilirubin at VOD diagnosis were 1.0 and 0.2 mg/dL, respectively. All 5 patients were subsequently diagnosed with multiorgan failure associated with VOD, including 1 with encephalopathy. Four were treated with intravenous high-dose methylprednisolone (500 mg/m(2) per dose every 12 hours for 6 doses). One patient received defibrotide therapy in addition to steroids and another supportive care alone. VOD resolved in 4 of 5 patients, with median time to resolution of VOD, defined as recovery of all organ function and normalization of bilirubin and portal venous flow, of 8 days. Two patients died later from progressive primary disease and chronic graft-versus-host disease, respectively. We conclude that a high index of suspicion for VOD should be maintained in patients despite lack of bilirubin elevation in the presence of other diagnostic criteria such as hepatomegaly, abdominal pain, ascites, or weight gain. Early ultrasound evaluation in these patients may lead to more timely diagnosis and therapeutic interventions.
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio. Electronic address: kasiani.myers@cchmc.org.
authors.forename: Kasiani C
authors.initials: KC
authors.lastname: Myers
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Christopher
authors.initials: C
authors.lastname: Dandoy
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Javier
authors.initials: J
authors.lastname: El-Bietar
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Stella M
authors.initials: SM
authors.lastname: Davies
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jodele
mesh_terms: D000293:Adolescent; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001663:Bilirubin / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006504:Hepatic Veno-Occlusive Disease / Q000175:diagnosis* / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007938:Leukemia / Q000276:immunology / Q000473:pathology / Q000628:therapy; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use; D009102:Multiple Organ Failure / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D009447:Neuroblastoma / Q000276:immunology / Q000473:pathology / Q000628:therapy; D011089:Polydeoxyribonucleotides / Q000627:therapeutic use; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D000893:Anti-Inflammatory Agents; D005343:Fibrinolytic Agents; D007166:Immunosuppressive Agents; D011089:Polydeoxyribonucleotides; C036901:defibrotide; D001663:Bilirubin; D008775:Methylprednisolone
keywords: Hematopoietic stem cell transplantation; High-dose steroids; Liver; Pediatrics; VOD