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Progressive Familial Intrahepatic Cholestasis Medication

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

Medication Summary

For information on most of the medications used to treat progressive familial intrahepatic cholestasis (PFIC), including antipruritic therapy and fat-soluble vitamins, see the Medscape Reference article Cholestasis.

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Gallstone-solubilizing agents

Class Summary

Ursodeoxycholic acid (ursodiol), a naturally occurring bile acid present in small quantities in human bile, suppresses liver synthesis, suppresses secretion of cholesterol, and inhibits intestinal cholesterol absorption.

Ursodiol (Actigall, URSO)

 

Also called ursodeoxycholic acid. Shown to promote bile flow in cholestatic conditions associated with patent extrahepatic biliary system. Decreases cholesterol content of bile and decreases likelihood of sludging and bile stones. Hydrophilic bile acid thought to act by decreasing overall toxicity of bile acid pool.

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Bile-acid binding agents

Class Summary

These agents are FDA approved for pruritus caused by biliary stasis.

Cholestyramine (Prevalite, Questran)

 

Forms a nonabsorbable complex with bile acids in the intestine, which in turn inhibits enterohepatic reuptake of intestinal bile salts. Take other medications at least 1 h before or 4-6 h after cholestyramine.

Not to be administered in dry powder form. Mix with plenty of water or applesauce.

May use as adjunct in primary hypercholesterolemia.

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Hepatic enzyme inducers

Class Summary

These agents are used to induce activity of hepatic enzymes, thus enhancing bilirubin excretion, which may improve function in some patients with cholestasis. An antipruritic effect is noticed with reduction of serum bilirubin.

Phenobarbital (Luminal)

 

Mainly used as an anticonvulsant that interferes with transmission of impulses from thalamus to cortex of brain, causing an imbalance in central inhibitory and facilitatory mechanisms. Used in cholestasis to induce CYP450 system in treatment of neonatal hyperbilirubinemia and to lower bilirubin in chronic cholestasis.

Rifampin (Rifadin, Rimactane)

 

Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which in turn blocks RNA transcription.

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Vitamins

Class Summary

Fat-soluble vitamins A, D, E, and K should be administered as individual supplements to ensure proper absorption.

Phytonadione (AquaMEPHYTON)

 

Vitamin K is a fat-soluble vitamin absorbed by the gut and stored in the liver. Necessary for function of clotting factors in coagulation cascade. Used to replace essential vitamins not obtained in sufficient quantities in diet or to further supplement levels.

Vitamin E (Liqui E)

 

Protects polyunsaturated fatty acids in membranes from attack by free radicals and protects RBCs against hemolysis.

Vitamin A (Aquasol A)

 

Needed for bone development, growth, visual adaptation to darkness, and testicular and ovarian function and as a cofactor in many biochemical processes.

Ergocalciferol (Calciferol, Drisdol)

 

Vitamin D stimulates absorption of calcium and phosphate from small intestine and promotes release of calcium from bone into blood; PO solution is 8000 U/mL (200 mcg/mL, 40 U/mcg).

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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
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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.
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
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