title: Two Case Reports of Successful Treatment of Cholestasis With Steroids in Patients With PFIC-2.
abstract: Mutations in the gene encoding the canalicular bile salt export pump (BSEP) can result in progressive familial intrahepatic cholestasis type 2 (PFIC-2). Treatment options are limited, and PFIC-2 often necessitates liver transplantation. We report on a young woman and a boy who clinically presented with PFIC-2 phenotypes and dramatically improved with steroid treatment. Gene sequencing of ABCB11 encoding for BSEP revealed 2 relevant mutations in both patients. The young woman was compound heterozygous for p.T919del and p.R1235X. At the age of 5 years, partial biliary diversion was performed and rescued liver function but left serum bile salt levels elevated. At age 23 she developed systemic lupus erythematosus. Unexpectedly, steroid therapy normalized serum bile salt levels, with a strong correlation with the steroid dose. She is currently in clinical remission. The boy was compound heterozygous for the ABCB11 mutations c.150+3A>C and p.R832C and presented with intractable pruritus. When he developed colitis, he was treated with steroids. The pruritus completely disappeared and relapsed when steroids were withdrawn. To date, with low-dose budesonide, the boy has been symptom-free for >3 years. In conclusion, the clinical courses suggest that patients with BSEP deficiency and residual BSEP activity may benefit from steroid-based therapy, which represents a new treatment option.
authors.affiliation: Department of Pediatrics, Lukashospital, Neuss, Germany; engelmann@lukasneuss.de.
authors.forename: Guido
authors.initials: G
authors.lastname: Engelmann
authors.affiliation: Department of General Pediatrics, University Hospital Heidelberg, Ruprecht-Karls-University, Heidelberg, Germany;
authors.forename: Daniel
authors.initials: D
authors.lastname: Wenning
authors.affiliation: Departments of General Pediatrics, Neonatology and Pediatric Cardiology.
authors.forename: Diran
authors.initials: D
authors.lastname: Herebian
authors.affiliation: Rheumatology, and.
authors.forename: Oliver
authors.initials: O
authors.lastname: Sander
authors.affiliation: Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany; and.
authors.forename: Carola
authors.initials: C
authors.lastname: Dröge
authors.affiliation: Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany; and.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kluge
authors.affiliation: Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Heinrich-Heine-University, Düsseldorf, Germany; and Medical Clinic I, Bethanien Hospital, Moers, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kubitz
mesh_terms: D019819:Budesonide / Q000627:therapeutic use*; D002648:Child; D002780:Cholestasis, Intrahepatic / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D009154:Mutation; D011239:Prednisolone / Q000627:therapeutic use*; D012074:Remission Induction; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D019819:Budesonide; D011239:Prednisolone
keywords: BSEP; progressive familial intrahepatic cholestasis; pruritus; therapy