Progressive Familial Intrahepatic Cholestasis Treatment & Management

  • Author: Joshua R Friedman, MD, PhD; Chief Editor: Carmen Cuffari, MD   more...
 
Updated: Oct 26, 2011
 

Medical Care

The general treatment of cholestasis applies to progressive familial intrahepatic cholestasis; please see the article Cholestasis for treatment information. The disease typically does not respond to any form of medical therapy. Some have reported success in treating patients with progressive familial intrahepatic cholestasis with ursodeoxycholic acid (20-30 mg/kg/d), which may be tried as an initial treatment. Other therapies for the symptomatic relief of pruritus include antihistamines, rifampin, and bile acid-binding agents.

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Surgical Care

Surgical therapy that diverts bile salts from the enterohepatic recirculation relieves pruritus in most patients, decreases serum bile salt levels, improves growth, and may delay the progression of disease with PFIC1 and PFIC2. The most common procedure, partial cutaneous biliary diversion, diverts gallbladder bile to a cutaneous ostomy. Patients typically drain 30-120 mL of bile per day, which is discarded. In a recent study following children with PFIC, 3 years after diversion procedure, 45% of patients had complete relief of pruritus, 27% had mild pruritus, and 27% experienced no relief.[8, 9, 10, 11, 12]

Liver transplantation is indicated in patients with decompensated cirrhosis or with a failed diversion with debilitating pruritus. The clinical courses and outcomes for PFIC1 recipients after living-donor liver transplantation are still not that good when compared with PFIC2 recipients. Hori et al reported 14 PFIC patients who underwent living-donor liver transplantation, comprising 11 PFIC1 and 3 PFIC2 patients. Three of 11 PFIC1 recipients died, while the 3 recipients with PFIC2 survived.[13] Liver transplantation is the only effective treatment of PFIC3.[10]

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Consultations

Refer all patients to centers with expertise in pediatric hepatology.

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Diet

The treatment of fat malabsorption principally involves dietary substitution. In an older patient, a diet rich in carbohydrates and proteins can be substituted for a diet containing long-chain triglycerides. This may not be possible for infants, for whom substitution of a formula containing medium-chain triglycerides may improve fat absorption and nutrition. However, this substitution has not been proven, and therapeutic formulas containing medium-chain triglycerides may not be worth the expense. Bile salt therapy to replace missing bile salts is not practical. Ursodeoxycholic acid, which is used to treat some cholestatic conditions, does not form mixed micelles and has no effect on fat absorption.

Pay careful attention to preventing fat-soluble vitamin deficiencies, accomplished by administering fat-soluble vitamins and monitoring the response to therapy. Administer vitamin E as tocopherol polyethylene glycol succinate (TPGS) to achieve sufficient absorption in the face of reduced intestinal bile salt concentrations.

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Activity

No activity restrictions are needed until late stages of liver disease when precautions should be taken to avoid splenic injury.

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Contributor Information and Disclosures
Author

Joshua R Friedman, MD, PhD  Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine; Attending Physician, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia

Joshua R Friedman, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Study of Liver Diseases, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Pfizer, Inc. Ownership interest None; Johnson & Johnson Ownership interest None

Coauthor(s)

Amanda Brooke Muir, MD  Resident Physician, Department of Pediatrics, Children's Hospital of Philadelphia

Amanda Brooke Muir, MD is a member of the following medical societies: American Academy of Pediatrics and American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H  Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan Faculty of Medicine, Jordan

Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H is a member of the following medical societies: Royal College of Paediatrics and Child Health, Royal College of Physicians, Royal College of Surgeons in Ireland, Royal College of Surgeons of Edinburgh, and Royal Society of Tropical Medicine and Hygiene

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Stefano Guandalini, MD  Director, Celiac Disease Center, Chief, Section of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Chicago Medical Center; Professor, Department of Pediatrics, Section of Gastroenterology, Hepatology and Nutrition, University of Chicago Division of the Biological Sciences, The Pritzker School of Medicine

Stefano Guandalini, MD is a member of the following medical societies: American Gastroenterological Association, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, and North American Society for Pediatric Gastroenterology and Nutrition

Disclosure: Nothing to disclose.

Steven M Schwarz, MD, FAAP, FACN, AGAF  Professor of Pediatrics, Children's Hospital at Downstate, State University of New York Downstate Medical Center

Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research

Disclosure: Curemark, LLC Consulting fee Board membership; Centocor, Inc. Grant/research funds Independent contractor; Johnson & Johnson, Inc. Grant/research funds Independent contractor

Chief Editor

Carmen Cuffari, MD  Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine

Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

References

  1. Davit-Spraul A, Gonzales E, Baussan C, Jacquemin E. Progressive familial intrahepatic cholestasis. Orphanet J Rare Dis. Jan 8 2009;4:1. [Medline].

  2. Alissa FT, Jaffe R, Shneider BL. Update on progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. Mar 2008;46(3):241-52. [Medline].

  3. Wang L, Dong H, Soroka CJ, Wei N, Boyer JL, Hochstrasser M. Degradation of the bile salt export pump at endoplasmic reticulum in progressive familial intrahepatic cholestasis type II. Hepatology. Nov 2008;48(5):1558-69. [Medline].

  4. Espinosa Fernandez MG, Navas Lopez VM, Blasco Alonso J, Sierra Salinas C, Barco Galvez A. [Progressive familial intrahepatic cholestasis type 3. An MDR3 defect]. An Pediatr (Barc). Aug 2008;69(2):182-4. [Medline].

  5. Knisely AS, Strautnieks SS, Meier Y, Stieger B, Byrne JA, Portmann BC, et al. Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency. Hepatology. Aug 2006;44(2):478-86. [Medline].

  6. Chen ST, Chen HL, Su YN, et al. Prenatal diagnosis of progressive familial intrahepatic cholestasis type 2. J Gastroenterol Hepatol. Sep 2008;23(9):1390-3. [Medline].

  7. Liu C, Aronow BJ, Jegga AG, Wang N, Miethke A, Mourya R, et al. Novel resequencing chip customized to diagnose mutations in patients with inherited syndromes of intrahepatic cholestasis. Gastroenterology. Jan 2007;132(1):119-26. [Medline].

  8. Ekinci S, Karnak I, Gurakan F, et al. Partial external biliary diversion for the treatment of intractable pruritus in children with progressive familial intrahepatic cholestasis: report of two cases. Surg Today. 2008;38(8):726-30. [Medline].

  9. Arnell H, Bergdahl S, Papadogiannakis N, Nemeth A, Fischler B. Preoperative observations and short-term outcome after partial external biliary diversion in 13 patients with progressive familial intrahepatic cholestasis. J Pediatr Surg. Jul 2008;43(7):1312-20. [Medline].

  10. Usui M, Isaji S, Das BC, et al. Liver retransplantation with external biliary diversion for progressive familial intrahepatic cholestasis type 1: A case report. Pediatr Transplant. Sep 10 2008;[Medline].

  11. Alonso EM, Snover DC, Montag A, et al. Histologic pathology of the liver in progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. Feb 1994;18(2):128-33. [Medline].

  12. Yang H, Porte RJ, Verkade HJ, De Langen ZJ, Hulscher JB. Partial external biliary diversion in children with progressive familial intrahepatic cholestasis and Alagille disease. J Pediatr Gastroenterol Nutr. Aug 2009;49(2):216-21. [Medline].

  13. Hori T, Egawa H, Takada Y, et al. Progressive familial intrahepatic cholestasis: a single-center experience of living-donor liver transplantation during two decades in Japan. Clin Transplant. Sep 2011;25(5):776-785. [Medline].

  14. Bull LN, van Eijk MJ, Pawlikowska L, et al. A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis. Nat Genet. Mar 1998;18(3):219-24. [Medline].

  15. Davis AR, Rosenthal P, Newman TB. Nontransplant surgical interventions in progressive familial intrahepatic cholestasis. J Pediatr Surg. Apr 2009;44(4):821-7. [Medline].

  16. de Vree JM, Jacquemin E, Sturm E, et al. Mutations in the MDR3 gene cause progressive familial intrahepatic cholestasis. Proc Natl Acad Sci U S A. Jan 6 1998;95(1):282-7. [Medline].

  17. Deleuze JF, Jacquemin E, Dubuisson C, et al. Defect of multidrug-resistance 3 gene expression in a subtype of progressive familial intrahepatic cholestasis. Hepatology. Apr 1996;23(4):904-8. [Medline].

  18. Emond JC, Whitington PF. Selective surgical management of progressive familial intrahepatic cholestasis (Byler's disease). J Pediatr Surg. Dec 1995;30(12):1635-41. [Medline].

  19. Hollands CM, Rivera-Pedrogo FJ, Gonzalez-Vallina R, et al. Ileal exclusion for Byler's disease: an alternative surgical approach with promising early results for pruritus. J Pediatr Surg. Feb 1998;33(2):220-4. [Medline].

  20. Jacquemin E. Progressive familial intrahepatic cholestasis. J Gastroenterol Hepatol. Jun 1999;14(6):594-9. [Medline].

  21. Jacquemin E, Hermans D, Myara A, et al. Ursodeoxycholic acid therapy in pediatric patients with progressive familial intrahepatic cholestasis. Hepatology. Mar 1997;25(3):519-23. [Medline].

  22. Jansen PL, Strautnieks SS, Jacquemin E, et al. Hepatocanalicular bile salt export pump deficiency in patients with progressive familial intrahepatic cholestasis. Gastroenterology. Dec 1999;117(6):1370-9. [Medline].

  23. Strautnieks SS, Bull LN, Knisely AS, et al. A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis. Nat Genet. Nov 1998;20(3):233-8. [Medline].

  24. van Mil SW, Houwen RH, Klomp LW. Genetics of familial intrahepatic cholestasis syndromes. J Med Genet. Jun 2005;42(6):449-63. [Medline]. [Full Text].

  25. van Mil SW, van der Woerd WL, van der Brugge G, et al. Benign recurrent intrahepatic cholestasis type 2 is caused by mutations in ABCB11. Gastroenterology. Aug 2004;127(2):379-84. [Medline].

  26. Wagner M, Trauner M. Transcriptional regulation of hepatobiliary transport systems in health and disease: implications for a rationale approach to the treatment of intrahepatic cholestasis. Ann Hepatol. Apr-Jun 2005;4(2):77-99. [Medline].

  27. Whitington PF, Freese DK, Alonso EM, et al. Clinical and biochemical findings in progressive familial intrahepatic cholestasis. J Pediatr Gastroenterol Nutr. Feb 1994;18(2):134-41. [Medline].

  28. Whitington PF, Whitington GL. Partial external diversion of bile for the treatment of intractable pruritus associated with intrahepatic cholestasis. Gastroenterology. Jul 1988;95(1):130-6. [Medline].

 
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Progressive familial intrahepatic cholestasis (PFIC), typical findings. Ballooned hepatocytes from cholate injury, scattered giant cells, cholestasis, and lacy fibrosis extending from central veins to portal areas.
Ballooned hepatocytes with cholestasis and some giant cell transformation. Note the sinusoidal lacy fibrosis.
 
 
 
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