title: Allograft steatohepatitis in progressive familial intrahepatic cholestasis type 1 after living donor liver transplantation.
abstract: We studied histological features and long-term outcomes in patients with progressive familial intrahepatic cholestasis type 1 (PFIC1) after liver transplantation (LT). Histological findings were correlated with the post-LT course and treatment in 11 recipients with PFIC1. Ages at LT varied from 1 to 18 years (median, 4 years). Macrovesicular steatosis was observed in 8 patients at a median of 60 days post-LT (range, 21-191 days). Severe steatosis progressed to steatohepatitis in 7 patients at a median of 161 days (range, 116-932 days). The patients were followed up for a median of 7.3 years (range, 2.3-16.1 years). Six showed bridging fibrosis, with 2 progressing to cirrhosis. One patient with cirrhosis died because of the rupture of a splenic artery aneurysm 13.6 years post-LT. Post-LT refractory diarrhea was present in all 8 having steatosis. Three without post-LT diarrhea showed no allograft steatosis. Bile adsorptive resin therapy reduced the diarrhea and steatosis. Patients with posttransplant steatosis typically had more severe mutations of the ATPase class I type 8B member 1 (ATP8B1) gene and were more likely to have systemic complications such as pancreatitis. In conclusion, allograft steatosis was present in patients with PFIC1, progressing to steatohepatitis and cirrhosis. Because expression of the familial intrahepatic cholestasis 1 gene occurs in several organs, including the small intestine, pancreas, and liver, and it is involved in enterohepatic bile acid circulation, post-LT steatosis may be due to a malfunction of the ATP8B1 product.
authors.affiliation: Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Miyagawa-Hayashino
authors.forename: Hiroto
authors.initials: H
authors.lastname: Egawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Yorifuji
authors.forename: Makoto
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Hironori
authors.initials: H
authors.lastname: Haga
authors.forename: Tatsuaki
authors.initials: T
authors.lastname: Tsuruyama
authors.forename: Mei-Chin
authors.initials: MC
authors.lastname: Wen
authors.forename: Ryo
authors.initials: R
authors.lastname: Sumazaki
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Manabe
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D018450:Disease Progression; D005234:Fatty Liver / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000235:genetics; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D012189:Retrospective Studies; D014184:Transplantation, Homologous
chemical_list: D000251:Adenosine Triphosphatases; C111067:ATP8B1 protein, human