Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Progressive Familial Intrahepatic Cholestasis Clinical Presentation

  • Author: Melissa Kennedy, MD; Chief Editor: Carmen Cuffari, MD  more...
 
Updated: Nov 19, 2015
 

History

The following may be noted in the history of a patient with progressive familial intrahepatic cholestasis (PFIC)

Next

Physical

See the list below:

  • Pruritus
    • Scratching
    • Cutaneous mutilation
    • Irritability in infants
  • Jaundice
    • Scleral icterus
    • Cutaneous jaundice
  • Hepatomegaly
  • Splenomegaly
  • Altered anthropometrics
  • Reduced height
  • Reduced weight for height
Previous
Next

Causes

See the list below:

  • Progressive familial intrahepatic cholestasis is a genetically determined autosomal recessive disorder.
  • Consanguinity is a major risk factor.[8]
Previous
 
 
Contributor Information and Disclosures
Author

Melissa Kennedy, MD Attending Physician, Division of Gastroenterology, Hepatology, and Nutrition, Children's Hospital of Philadelphia

Melissa Kennedy, MD is a member of the following medical societies: American Academy of Pediatrics, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Nothing to disclose.

Coauthor(s)

Joshua R Friedman, MD, PhD Adjunct Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

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, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition

Disclosure: Received salary from Johnson & Johnson for employment.

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, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

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 Founder and Medical 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, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, European Society for Paediatric Gastroenterology, Hepatology & Nutrition, North American Society for the Study of Celiac Disease

Disclosure: Received consulting fee from AbbVie for consulting.

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, Royal College of Physicians and Surgeons of Canada

Disclosure: Received honoraria from Prometheus Laboratories for speaking and teaching; Received honoraria from Abbott Nutritionals for speaking and teaching.

Additional Contributors

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

Hisham Nazer, MB, BCh, FRCP, , DTM&H is a member of the following medical societies: American Association for Physician Leadership, Royal College of Paediatrics and Child Health, Royal College of Surgeons in Ireland, Royal Society of Tropical Medicine and Hygiene, Royal College of Physicians and Surgeons of the United Kingdom

Disclosure: Nothing to disclose.

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

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

  3. van der Woerd WL, van Mil SW, Stapelbroek JM, Klomp LW, van de Graaf SF, Houwen RH. Familial cholestasis: progressive familial intrahepatic cholestasis, benign recurrent intrahepatic cholestasis and intrahepatic cholestasis of pregnancy. Best Pract Res Clin Gastroenterol. 2010 Oct. 24(5):541-53. [Medline].

  4. Varma S, Revencu N, Stephenne X, Scheers I, Smets F, Beleza-Meireles A, et al. Retargeting of bile salt export pump and favorable outcome in children with progressive familial intrahepatic cholestasis type 2. Hepatology. 2015 Jul. 62 (1):198-206. [Medline].

  5. 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. 2008 Nov. 48(5):1558-69. [Medline].

  6. 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). 2008 Aug. 69(2):182-4. [Medline].

  7. Delaunay JL, Durand-Schneider AM, Dossier C, Falguières T, Gautherot J, Anne DS, et al. A functional classification of ABCB4 variations causing progressive familial intrahepatic cholestasis type 3. Hepatology. 2015 Oct 17. [Medline].

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

  9. 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. 2007 Jan. 132(1):119-26. [Medline].

  10. Gunaydin M, Tander B, Demirel D, Caltepe G, Kalayci AG, Eren E, et al. Different techniques for biliary diversion in progressive familial intrahepatic cholestasis. J Pediatr Surg. 2015 Aug 22. [Medline].

  11. van der Woerd WL, Kokke FT, van der Zee DC, Houwen RH. Total biliary diversion as a treatment option for patients with progressive familial intrahepatic cholestasis and Alagille syndrome. J Pediatr Surg. 2015 Jul 27. [Medline].

  12. Jankowska I, Socha P. Progressive familial intrahepatic cholestasis and inborn errors of bile acid synthesis. Clin Res Hepatol Gastroenterol. 2012 Jun. 36(3):271-4. [Medline].

  13. Kalicinski PJ, Ismail H, Jankowska I, Kaminski A, Pawlowska J, Drewniak T. Surgical treatment of progressive familial intrahepatic cholestasis: comparison of partial external biliary diversion and ileal bypass. Eur J Pediatr Surg. 2003 Oct. 13(5):307-11. [Medline].

  14. 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. 2006 Aug. 44(2):478-86. [Medline].

  15. 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].

  16. 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. 2008 Jul. 43(7):1312-20. [Medline].

  17. 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. 2008 Sep 10. [Medline].

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

  19. 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. 2009 Aug. 49(2):216-21. [Medline].

  20. 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. 2011 Sep. 25(5):776-785. [Medline].

  21. 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. 1998 Mar. 18(3):219-24. [Medline].

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

  23. 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. 1998 Jan 6. 95(1):282-7. [Medline].

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

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

  26. 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. 1998 Feb. 33(2):220-4. [Medline].

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

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

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

  30. 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. 1998 Nov. 20(3):233-8. [Medline].

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

  32. 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. 2004 Aug. 127(2):379-84. [Medline].

  33. 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. 2005 Apr-Jun. 4(2):77-99. [Medline].

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

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

  36. Strautnieks SS, Byrne JA, Pawlikowska L, Cebecauerová D, Rayner A, Dutton L, et al. Severe bile salt export pump deficiency: 82 different ABCB11 mutations in 109 families. Gastroenterology. 2008 Apr. 134(4):1203-14. [Medline].

Previous
Next
 
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.
Table 1.
GeneProteinProposed



Pathophysiology



GGTClinical considerations
ATP8B1FIC 1 (ATP8B1)Increased phospholipid membrane instability leads to decreased bile acid transportLowExtrahepatic manifestations: diarrhea, pancreatitis, hearing loss
ABCB11BPEPMutation in bile acid export pump (BSEP) leads to cholestasisLowIncreased risk of hepatobiliary malignancies
ABCB4MDR3Decreased phospholipid concentration in bile leads to destabilized micelles within ductules causing inflammation/destruction and eventually cholestasisHighOnset of cholestasis tends to be later in life
Previous
Next
 
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.