Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

Abstract

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.

Long-Term Outcome after Liver Transplantation for Progressive Familial Intrahepatic Cholestasis

“…Progression of PFIC may temporarily present a clinical and laboratory improvement through drug therapies (rifampicin, ursodeoxycholic acid, cholestyramine, phenobarbital) or through biliary diversion (BD) in the absence of liver cirrhosis [ 27 , 28 , 29 ]. Even if there is no full manifestation of liver cirrhosis, liver transplantation (LT), especially for PFIC1, might also be the therapy of choice, since the PFIC-specific itching and jaundice can lead to serious developmental disorders, accompanied by retarded growth, severe rickets and reduction in quality of life [ 1 , 2 , 3 , 12 , 19 , 30 , 31 , 32 , 33 , 34 ]. LT for PFIC1 proves to be feasible regardless of donor type and reduces failure to thrive and permanent itching [ 19 , 30 , 35 , 36 ].…”

“…Even if there is no full manifestation of liver cirrhosis, liver transplantation (LT), especially for PFIC1, might also be the therapy of choice, since the PFIC-specific itching and jaundice can lead to serious developmental disorders, accompanied by retarded growth, severe rickets and reduction in quality of life [ 1 , 2 , 3 , 12 , 19 , 30 , 31 , 32 , 33 , 34 ]. LT for PFIC1 proves to be feasible regardless of donor type and reduces failure to thrive and permanent itching [ 19 , 30 , 35 , 36 ]. The analysis of our patient cohort showed an excellent course for all transplant types.…”

“…Liver transplantation (LT) is an important therapeutic tool for the management of PFIC [ 19 , 20 ]. In the course of transplantation, a decrease in cholestasis has been observed, and the occurrence of PFIC1-specific extrahepatic manifestation was also described in the literature.…”

Biopsy Validated Study of Biomarkers for Liver Fibrosis and Transplant Prediction in Inherited Cholestasis

“…These findings support that elevated or rising APRI may be associated with hepatic disease progression in ALGS and PFIC with suggested biopsy-validated cutoffs for clinical prediction of severity of fibrosis. Although clinical decision making in children with ALGS or PFIC is often based on the development of extrahepatic manifestations such as intractable pruritus, disfiguring xanthomas, and severe malnutrition from persistent cholestasis, (2,4,32) identification of worsening fibrosis severity in these children remains an important prognostic variable, as advanced stages of fibrosis not only lead to complications from cirrhosis but contribute to and parallel the severity of these extrahepatic features. Therefore, despite a somewhat limited sensitivity, APRI appears to be a readily available, noninvasive tool that may complement the overall decision-making process in children with rare cholestatic disorders.…”

“…Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) represent distinct but rare inherited cholestatic disorders that display wide variability in degrees of liver fibrosis, progression of disease, and time to transplant. ( 1‐8 ) Although genetic analysis is emphasized for either diagnosis, percutaneous liver biopsy has historically been an essential tool for histologic staging and monitoring progression of disease. ( 9,10 ) Risks of liver biopsies are relatively low; however, there is still potential for bleeding, patient discomfort, infection, and side effects of anesthesia.…”