Introduction: Routine evaluation fails to identify a cause for acute liver failure in 50% of children. In a case series of 4 pediatric patients, a clinical protocol including immunohistochemical staining of liver tissue was used to identify and treat atypical immune-mediated causes of acute liver injury.
Methods: Laboratory screening for genetic, metabolic, autoimmune (IgG, ANA, Anti-LK, Anti-Sm) and infectious studies from blood and tissue were performed. Liver biopsies were stained by the Stanford Immunoperoxidase Laboratory for antibodies to CD3/4/8/20/56/138 and 163. Viral PCR and staining for EBV, CMV, parvovirus and adenovirus was conducted as appropriate.
Results: All patients presented with baseline AST and ALT (1959-4700), T bili (7.8-14.5), INR (1.2-2.6). Genetic, metabolic and autoimmune markers were negative in 3 cases. Two patients elevated IgG levels and one patient had positive Anti-Sm 1:20 and ANA 1:320. All patients were male and ages 2-12. Infectious studies including serology for EBV, CMV, Hepatitis A-C were negative for acute infection. Liver biopsy in all cases showed acute hepatitis with predominance of cytotoxic CD8 T-cells and paucity of CD4 and CD20 B-cells. All were treated with 0.4-1 gm/kg of IVIG, 2 mg/kg of solumedrol (maximum dose 60 mg) followed by a prednisone taper. In all cases, AST and ALT decreased to 50% at 48 hours and normalized by 3 months in all patients. Total bilirubin normalized by 1 month and INR by 2-6 days in all cases. No patients required liver transplantation.
Conclusions: A novel protocol involving early liver biopsy, lab testing and immunohistochemical staining successfully identified and treated four CD8 T-cell mediated causes of acute hepatitis in male children. Current guidelines for routine evaluation of acute liver injury may fail to identify these atypical cases that might respond to immunomodulator therapy. Further studies are needed to better identify and characterize these patients that may otherwise progress to liver failure and require transplantation if left untreated.
To cite this abstract in AMA style:McKenzie R, Berquist W, Nadeau K, Chen S, Sibley R, Cox K. Use of a Novel Protocol to Successfully Characterize and Treat Immune-Mediated Acute Hepatitis and Liver Failure in Children [abstract]. Am J Transplant. 2013; 13 (suppl 5). http://atcmeetingabstracts.com/abstract/use-of-a-novel-protocol-to-successfully-characterize-and-treat-immune-mediated-acute-hepatitis-and-liver-failure-in-children/. Accessed June 25, 2017.
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