Progressive Familial Intrahepatic Cholestasis Treatment & Management
- Author: Melissa Kennedy, MD; Chief Editor: Carmen Cuffari, MD more...
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.
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.[10, 11] 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] This procedure must be done prior to the development cirrhosis to be effective. Alternatively, ileal bypass, a procedure in which the proximal ileum is attached to the cecum bypassing the distal 15% of the ileum and therefore avoiding ileal reabsorption of bile acids can be performed in patients that are not candidates for diversion. This procedure provides immediate relief similar the results seen in diversion, but cholestasis eventually returns in most patients.
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. Liver transplantation is the only effective treatment of PFIC3.
Refer all patients to centers with expertise in pediatric hepatology.
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.
No activity restrictions are needed until late stages of liver disease when precautions should be taken to avoid splenic injury.
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|ATP8B1||FIC 1 (ATP8B1)||Increased phospholipid membrane instability leads to decreased bile acid transport||Low||Extrahepatic manifestations: diarrhea, pancreatitis, hearing loss|
|ABCB11||BPEP||Mutation in bile acid export pump (BSEP) leads to cholestasis||Low||Increased risk of hepatobiliary malignancies|
|ABCB4||MDR3||Decreased phospholipid concentration in bile leads to destabilized micelles within ductules causing inflammation/destruction and eventually cholestasis||High||Onset of cholestasis tends to be later in life|