ABSTRACT
INTRODUCTION: Nonobstructive cholestasis after pediatric liver transplantation is a common diagnostic and therapeutic dilemma. We describe a girl with neonatal cholestasis because of progressive familial intrahepatic cholestasis 2 (PFIC-2) and presence of a homozygous splice site mutation in the ABCB11 gene. Liver transplantation was performed because of end-stage liver disease at the age of 6. Cholestasis with normal gamma-glutamyl transferase (GGT) developed 8 years after liver transplantation. A liver biopsy showed canalicular cholestasis and giant cell hepatitis without evidence of rejection, mimicking PFIC-2. Immunofluorescence staining of normal human liver sections with patient's serum revealed reactivity toward a canalicular epitope, which could be identified as bile salt export pump (BSEP) using BSEP-yellow fluorescent protein (YFP) transfected cells. Our patient developed a recurrence of a PFIC-2 phenotype due to production of antibodies against BSEP (alloimmune BSEP disease [AIBD]). Intensification of immunosuppressive therapy as well as antibody treatment with plasmapheresis and Rituximab were initiated, leading to stabilization of the clinical condition and depletion of anti-BSEP antibodies in serum. However, after 1 year liver transplantation was necessary again because of end-stage liver insufficiency. Afterward, immunomodulatory treatment consisted of tacrolimus, mycophenolate mofetil, prednisone, immunoadsorption, and high-dose immunoglobulin therapy (1 g/kg/d). CONCLUSION: Cholestasis after liver transplantation may indicate an AIBD with a PFIC-2 phenotype. Besides enhancement of immunosuppressive therapy, an antibody depletion with plasmapheresis, immunoadsorption, immunoglobulins, and B-cell depletion represents a therapeutic option.
Subject(s)
Cholestasis, Intrahepatic/immunology , End Stage Liver Disease/immunology , Immunosuppressive Agents/therapeutic use , Liver Transplantation/adverse effects , Plasmapheresis/methods , ATP Binding Cassette Transporter, Subfamily B, Member 11/genetics , ATP Binding Cassette Transporter, Subfamily B, Member 11/immunology , Adolescent , Antibodies/blood , Antibodies/immunology , B-Lymphocytes/immunology , Child , Cholestasis, Intrahepatic/complications , Cholestasis, Intrahepatic/genetics , Diagnosis, Differential , End Stage Liver Disease/genetics , End Stage Liver Disease/surgery , Epitopes , Female , Humans , Immunologic Factors/therapeutic use , Immunosuppression Therapy/methods , Mutation , Phenotype , Postoperative Period , Recurrence , Reoperation/methods , Rituximab/therapeutic use , Treatment OutcomeABSTRACT
OBJECTIVE: The objective of this study was to analyze the effect of a fructose-restricted diet in otherwise healthy children with abdominal pain and pathologic fructose hydrogen breath test. SUBJECTS AND METHODS: 75 children (aging 3-14 years) with recurrent abdominal pain without gastrointestinal disease and fructose malabsorption followed a fructose restricted diet for 4 weeks. RESULTS: A median decline of weekly pain frequency from 4 (mean 3.64+1.6) before diet to 1 (mean 1.46+1.4; p<0.001) under fructose restriction was documented. The intensity of pain decreased from median 6 (mean 5.83+2.0) before intervention to median 3 (mean 3.4+2.5; p<0.001) with diet. Several additional life quality-influencing parameters such as daily stool frequency, nausea, problems to fall asleep, missed school days also improved significantly. CONCLUSIONS: Our study provides evidence that dietary fructose restriction represents a useful approach to address recurrent abdominal symptoms in children with fructose malabsorption.