title: Late-Onset Drug-Induced Cholestasis in a Living-Related Liver Transplant Donor With Progressive Familial Intrahepatic Cholestasis.
abstract: We present a rare case of progressive familial intrahepatic cholestasis within a family. A 34-yearold female became a living-related liver transplant donor for her son, who had the disease. Nine years after the transplant, the mother developed severe intrahepatic cholestasis, for which she was evaluated after using an oral contraceptive drug. She presented with jaundice, pruritus, and increased bilirubin levels, together with elevated gamma glutamyl transferase and alkaline phosphatase levels. A liver biopsy revealed findings consistent with intrahepatic cholestasis. However, despite follow-up management and cessation of the insulting drug, her total bilirubin count continuously increased to 20 mg/dL and was accompanied by intractable pruritus. A total of 9 plasmapheresis sessions were performed, and she was started on a regimen of ursodeoxycholic acid (13 mg/kg/d) and cholestyramine (4 g, 3 times daily). The clinical and laboratory picture dramatically improved following cessation of the oral contraceptive, plasmapheresis sessions, and drug treatment. The patient's cholestasis normalized within 3 months, and she recovered uneventfully. A genetic analysis of the whole family revealed that both parents were heterozygous for the mutation c.124G>A in ABCB11, and the son was homozygous for this mutation. These findings supported varying degrees of bile salt export pump deficiency in the family members. Defective bile salt excretory system function can result in a wide spectrum of clinical presentations, ranging from progressive familial intrahepatic cholestasis requiring liver transplant to late-onset drug-induced cholestasis. Our findings suggest that, in a heterozygous carrier of a progressive familial intrahepatic cholestasis mutation, drug-induced cholestasis is responsive to treatment, after which the clinical picture can normalize within 3 months.
authors.affiliation: From the Department of Gastroenterology, Baskent University Faculty of Medicine, Ankara, Turkey.
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Harmancı
authors.forename: Fatih
authors.initials: F
authors.lastname: Ensaroğlu
authors.forename: Figen
authors.initials: F
authors.lastname: Özçay
authors.forename: Serkan
authors.initials: S
authors.lastname: Öcal
authors.forename: Murat
authors.initials: M
authors.lastname: Korkmaz
authors.forename: B Handan
authors.initials: BH
authors.lastname: Özdemir
authors.forename: Haldun
authors.initials: H
authors.lastname: Selçuk
authors.forename: Gökhan
authors.initials: G
authors.lastname: Moray
authors.forename: Mehmet
authors.initials: M
authors.lastname: Haberal
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D002780:Cholestasis, Intrahepatic / Q000175:diagnosis / Q000235:genetics*; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006498:Hepatectomy; D006579:Heterozygote; D006801:Humans; D016031:Liver Transplantation / Q000379:methods*; D019520:Living Donors; D009154:Mutation; D010641:Phenotype; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D015415:Biomarkers; D003278:Contraceptives, Oral, Hormonal; D001663:Bilirubin