Living‐donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

Hori, Tomohide; Egawa, Hiroto; Miyagawa‐Hayashino, Aya; Yorifuji, Tohru; Yonekawa, Yukihide; Nguyen, Justin H.; Üemoto, Shinji

doi:10.1007/s00268-010-0869-6

Cited by 18 publications

(32 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that their mild post-transplant hepatopathy is a consequence of the disruption of normal enterohepatic bile acid homeostasis. Post-transplant progressive hepatic steatosis has also been reported for PFIC1 (refs 23 , 24 ), perhaps due to altered FXR signaling 25 .…”

Section: Resultsmentioning

confidence: 89%

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

et al. 2016

View full text Add to dashboard Cite

Neonatal cholestasis is a potentially life-threatening condition requiring prompt diagnosis. Mutations in several different genes can cause progressive familial intrahepatic cholestasis, but known genes cannot account for all familial cases. Here we report four individuals from two unrelated families with neonatal cholestasis and mutations in NR1H4, which encodes the farnesoid X receptor (FXR), a bile acid-activated nuclear hormone receptor that regulates bile acid metabolism. Clinical features of severe, persistent NR1H4-related cholestasis include neonatal onset with rapid progression to end-stage liver disease, vitamin K-independent coagulopathy, low-to-normal serum gamma-glutamyl transferase activity, elevated serum alpha-fetoprotein and undetectable liver bile salt export pump (ABCB11) expression. Our findings demonstrate a pivotal function for FXR in bile acid homeostasis and liver protection.

show abstract

Section: Resultsmentioning

confidence: 89%

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Hori et al [ 7 , 8 ] reported on 14 patients who underwent living donor liver transplantation (LDLT) for PFIC (11 cases of PFIC1 and 3 cases of PFIC2). Three of the 11 PFIC1 recipients died, while all 3 PFIC2 recipients survived.…”

Section: Discussionmentioning

confidence: 99%

Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

et al. 2018

View full text Add to dashboard Cite

BackgroundProgressive familial intrahepatic cholestasis (PFIC) is an autosomal recessive inherited disease that disrupts the genes for bile formation. Liver transplantation (LT) is the only effective treatment for PFIC patients with end-stage liver disease. We describe our experience in terms of clinical characteristics, complications, and outcome of LT for PFIC.Case ReportThe data of 5 pediatric PFIC patients recipients (3 PFIC1, 1 PFIC2, and 1 PFIC3) who received LT at our Liver Transplant Center from June 2013 to February 2017 were retrospectively analyzed. Four patients received liver transplantation from donation after cardiac death (DCD) donors. One patient received a living donor liver transplantation (LDLT). All the LT recipients received an immunosuppressive regimen of tacrolimus (FK 506) + methylprednisolone + mycophenolate mofetil (MMF). Diarrhea did not improve in 2 PFIC1 patients after LT, and they both developed steatohepatitis several months after LT. The other PFIC1 patient received ABO blood group incompatible LT and developed biliary complications and a severe Epstein-Barr virus infection; this patient underwent endoscopic retrograde cholangiopancreatography. She recovered after treatment with ganciclovir and reduction of tacrolimus dosage. The PFIC2 patient had abnormal liver function 19 months after LT, and recovered after administration of increased dosage of immunosuppressant agents. Liver function in the PFIC3 patient was normal during 2-year follow-up.ConclusionsLiver transplantation is an effective treatment in PFIC patients. However, PFIC1 patients may develop aggravated diarrhea and steatohepatitis after LT. PFIC2 and PFIC3 patients have good outcomes after LT.

show abstract

“…The discussion with the parents was performed at multiple sittings giving them time to reflect and return with questions for clarifications. Firstly, parents were informed of what routine or standard practice was pertaining to their child, including the diagnosis, indication, timing, workup for LT, the possibility of postoperative problems in the local population (72.7% for graft steatosis and 90.9% for worsening diarrhea and malnutrition in one study), and the usual options following LT . One option was to proceed with regular Roux‐en‐Y hepaticojejunostomy without biliary diversion and only perform postoperative biliary diversion (either external or internal as per the literature) in case of problems.…”

Section: Discussionmentioning

confidence: 99%

“…Different authors report that LT for PFIC type 1 may be followed by persistent accumulation of bile acids within the graft, diarrhea, and malnutrition leading to graft steatosis and recurrent liver disease . After LT, bile acid‐adsorptive resin therapy has been employed with partial success at controlling digestive symptoms . However, only PEBD has demonstrated consistent symptomatic relief and recovery from graft steatosis, albeit at the price of an external stoma .…”

mentioning

confidence: 99%

“…2,3 After LT, bile acid-adsorptive resin therapy has been employed with partial success at controlling digestive symptoms. 4 However, only PEBD has demonstrated consistent symptomatic relief and recovery from graft steatosis, albeit at the price of an external stoma. 2,5 We report a case of PFIC type 1 wherein we applied TIBD preemptively during LT as a stoma-free procedure to prevent postoperative graft steatosis and recurrent liver disease.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach

Mali

Fukuda

Shigeta

et al. 2016

Pediatric Transplantation

View full text Add to dashboard Cite

LT for PFIC type 1 is often complicated by postoperative diarrhea and recurrent graft steatosis. A 26-month-old female child with cholestatic jaundice, pruritus, diarrhea, and growth retardation revealed total bilirubin 9.1 mg/dL, gamma-glutamyl transpeptidase 64 IU/L, and TBA 295.8 μmol/L. Genetic analysis confirmed ATP8B1 defects. A LT (segment 2, 3 graft) from the heterozygous father was performed. Biliary diversion was performed by a 35-cm jejunum conduit between the graft hepatic duct and the mid-transverse colon. Stools became pigmented immediately. Follow-up at 138 days revealed resolution of jaundice and pruritus and soft-to-hard stools (6-8 daily). Radioisotope hepato-biliary scintigraphy (days 26, 68, and 139) confirmed unobstructed bile drainage into the colon (t 34, 27, and 19 minutes, respectively). Contrast meal follow-through at day 62 confirmed the absence of any colo-jejuno-hepatic reflux. At 140 days, contrast follow-through via the biliary stent revealed patent jejuno-colonic anastomosis and satisfactory transit. Graft biopsy at LT, 138 days, and 9 months follow-up revealed comparable grades of macrovesicular steatosis (<20%). TIBD during LT may be a clinically effective stoma-free biliary diversion and may prevent recurrent graft steatosis following LT for PFIC type 1.

show abstract

Living‐donor Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

Cited by 18 publications

References 74 publications

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

Mutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis

Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

Total internal biliary diversion during liver transplantation for type 1 progressive familial intrahepatic cholestasis: a novel approach

Contact Info

Product

Resources

About