eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology
Cholestasis: Treatment & Medication
Updated: Jun 23, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
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Treatment
Medical Care
Much medical care in patients with cholestasis is disease specific; therefore, refer to articles about disease states (see Causes). Some medical care is specifically directed at cholestasis and its consequences.- Cholestasis often does not respond to medical therapy of any sort. Some reports indicate success in children with chronic cholestatic diseases with the use of ursodeoxycholic acid (20-30 mg/kg/d), which acts to increase bile formation and antagonizes the effect of hydrophobic bile acids on biological membranes. Phenobarbital (5 mg/kg/d) may also be useful in some children with chronic cholestasis. Opiate antagonists can block cholestasis-associated itching.
- The contribution of dietary cholesterol to the elevated serum cholesterol in patients with cholestasis is probably minimal, and limiting the diet in order to reduce serum cholesterol is not justified because that maneuver may have secondary effects on nutrition. Furthermore, oral bile salt–binding agents, such as cholestyramine, have little effect on serum cholesterol in this setting. Agents that block the synthesis of cholesterol have been used sparingly in cholestasis and cannot be recommended at this time. The proper approach to treating hypercholesterolemia in cholestatic liver disease is to treat the liver disease itself.
- Treatment of fat malabsorption principally involves dietary substitution. In older patients, a diet that is rich in carbohydrates and proteins can be substituted for a diet containing long-chain triglycerides. In infants, that may not be possible, and substitution of a formula containing medium-chain triglycerides may improve fat absorption and nutrition. This, however, has not clearly been proven, and therapeutic formulas containing medium-chain triglycerides may not be worth their 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.
- In chronic cholestasis, careful attention must be paid to prevent fat-soluble vitamin deficiencies. This is 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 setting of reduced intestinal bile salt concentrations.
Surgical Care
- Surgical care is disease specific; therefore, refer to articles about disease states (see Causes).
Consultations
- Referral to a specialist in gastroenterology or hepatology is indicated for any patient with cholestatic liver disease, particularly if it is severe or prolonged.
Diet
- See Medical Care.
Medication
Choleretic agents
Ursodeoxycholic acid acts to increase bile formation and antagonizes the effect of hydrophobic bile acids on biological membranes.
Ursodeoxycholic acid (Actigall, Urso)
Shown to promote bile flow in cholestatic conditions associated with a patent extrahepatic biliary system. Decreases the cholesterol content of bile and therefore reduces bile stone and sludge formation.
Adult
10-15 mg/kg/d PO divided bid
Pediatric
20-30 mg/kg/d PO divided bid
Decreased effect with aluminum-containing antacids, cholestyramine, colestipol, clofibrate, PO contraceptives, and activated charcoal
Documented hypersensitivity; need for cholecystectomy (ie, unremitting acute cholecystitis, cholangitis, biliary obstruction)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in patients with nonvisible gallbladder; GI effects include nausea, vomiting, diarrhea, or constipation; dermatologic effects including a rash; monitor hepatic enzymes
Barbiturates
These agents are used to induce hepatic enzyme metabolism in order to decrease serum bilirubin levels in some patients with cholestasis in order to improve function.
Phenobarbital (Luminal)
Mainly used as an anticonvulsant, which interferes with transmission of impulses from thalamus to cortex of brain, resulting in imbalance in central inhibitory and facilitatory mechanisms. Used in cholestasis to induce the CYP450 system in treatment of neonatal hyperbilirubinemia and lowering of bilirubin in chronic cholestasis.
Adult
Up to 30 mg/d PO has been described; adjust dose to maintain serum bilirubin levels within target range
Pediatric
5 mg/kg/d PO
May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of PO contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities may also occur)
Documented hypersensitivity; preexisting CNS depression; porphyria; severe respiratory disease with dyspnea or obstruction
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Vitamins
Fat-soluble vitamins A, D, E, and K must be administered as individual supplements to assure proper absorption.
Phytonadione (AquaMEPHYTON)
Vitamin K. Fat-soluble vitamin absorbed by the gut and stored in the liver. Necessary for the function of clotting factors in the coagulation cascade. Used to replace essential vitamins not obtained in sufficient quantities in the diet or to further supplement levels.
Adult
10 mg PO/IV/IM/SC should replenish the liver stores
Pediatric
1 mg IM
Effects of warfarin and dicumarol are antagonized by phytonadione
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Ineffective in hereditary hypoprothrombinemia; rapid infusion may result in flushing and a feeling of constriction in chest; relatively nontoxic, even in massive doses
Alpha tocopherol (Liqui E)
Vitamin E. Prevention and treatment of hemolytic anemia secondary to vitamin deficiency or need for dietary supplementation. Protects polyunsaturated fatty acids in membranes from attack by free radicals and protects RBC against hemolysis.
Adult
RDA dose: 8-10 mg/d PO (12-15 IU/d)
Therapeutic dose: 50-2000 IU/d PO
Deficiency: 30- to 50-mg tab/cap PO qd
(PO dose is usually 4-5 times the RDA)
Pediatric
RDA dose: 3-10 mg/d PO
Therapeutic dose: 1-100 mg/kg/d PO
Mineral oil decreases absorption of vitamin E; vitamin E delays absorption of iron and increases effects of anticoagulants
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Pregnancy category C with large doses; vitamin E may induce vitamin K deficiency; necrotizing enterocolitis may occur with large doses
Vitamin A (Aquasol A)
Needed for bone development, growth, visual adaptation to darkness, testicular and ovarian function, and as a cofactor in many biochemical processes.
Adult
Dietary supplement: 4000-5000 IU/d PO
RDA: 2670 IU/d (females) and 3330 IU/d (males)
Pediatric
Dietary supplement:
<6 months: 1500 IU/d PO
6 months to 3 years: 1500-2000 IU/d PO
4-6 years: 2500 IU/d PO
7-10 years: 3300-3500 IU/d PO
>10 years: Administer as in adults
Deficiency:
<1 year: 10,000 IU/kg/d IM for 5 d, then 7,500-15,000 IU/d for 10 d
1-8 years: 5,000-10,000 IU/kg/d IM for 5 d, then 17,000-35,000 IU/d for 10 d
>8 years: 100,000 IU/d IM for 3 d, then 50,000 IU/d for 14 d
Cholestyramine decreases absorption of vitamin A; neomycin and mineral oil may also interfere with vitamin A absorption
Documented hypersensitivity; hypervitaminosis A
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Pregnancy category X if dose exceeds RDA; evaluate other sources of vitamin A while receiving this product
Ergocalciferol (Drisdol, Calciferol)
Vitamin D. Stimulates absorption of calcium and phosphate from small intestine and promotes release of calcium from bone into blood. PO solution comes as 8000 U/mL (200 mcg/mL, 40 U/mcg).
Adult
10,000-80,000 U/d PO plus 1-2 g/d PO elemental phosphorus
Pediatric
Infants and healthy children: 10 mcg/d PO (400 U)
Vitamin D–dependent rickets: 75-125 mcg/d PO (3000-5000 U); not to exceed 1500 mcg/d
Nutritional rickets and osteomalacia: 25-125 mcg/d PO (1000-5000 U) in normal absorption; 250-650 mcg/d PO (10,000-25,000 U/d) in malabsorption
Colestipol, mineral oil, and cholestyramine may decrease absorption of ergocalciferol from small intestine; thiazide diuretics may increase effects of vitamin D
Documented hypersensitivity; hypercalcemia; malabsorption syndrome
Pregnancy
A - Fetal risk not revealed in controlled studies in humans
Precautions
Pregnancy category D if dose exceeds RDA; caution in impaired renal function, renal stones, heart disease, or arteriosclerosis
Opioid antagonists
These agents are used to alleviate pruritus caused by cholestasis. They block opioid-mediated pathways of afferent nerves, which may be producing the itching sensation.
Naltrexone (ReVia)
Cyclopropyl derivative of oxymorphone that acts as a competitive antagonist at opioid receptors. Do not administer this medication until the patient is opioid-free for 7-10 d. Available as 50-mg tab.
Adult
Initial dose: 25 mg PO; if no withdrawal signs within 1 h, administer another 25 mg
Maintenance dose: 50-150 mg 3 times/wk
Pediatric
10 mg/d PO increasing over 3-4 wk; not to exceed 25-30 mg/d
Inhibits opioid effects
Documented hypersensitivity; acute hepatitis; liver failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hepatic impairment
Bile salt resins
Bile acid–binding resins form a nonabsorbable complex with bile acids in the intestine, which inhibits enterohepatic reuptake of intestinal bile salts and thereby increases the fecal losses of bile salt–bound low-density lipoprotein cholesterol.
Cholestyramine (Questran, Prevalite)
May use as adjunct in primary hypercholesterolemia. Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts. Dose based on resin content.
Adult
4 g PO qd/bid; not to exceed 24 g/d or 6 doses/d; mix with water or juice and drink immediately
Pediatric
240 mg/kg/d PO divided tid; mix with water or juice and drink immediately
Inhibits absorption of numerous drugs, including warfarin, thyroid hormone, amiodarone, NSAIDs, methotrexate, digitalis glycosides, glipizide, phenytoin, imipramine, niacin, methyldopa, tetracyclines, clofibrate, hydrocortisone, and penicillin G
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in constipation and phenylketonuria
Antibiotics
Antitubercular agents induce liver enzymes and ameliorate pruritus secondary to cholestasis.
Rifampin (Rimactane, Rifadin)
Inhibits RNA synthesis in bacteria by binding to beta subunit of DNA-dependent RNA polymerase, which, in turn, blocks RNA transcription.
Adult
600 mg PO/IV qd
Pediatric
10-20 mg/kg/d PO/IV; not to exceed 600 mg/d
Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue 1 or both agents if alterations in LFT results occur)
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Obtain CBC counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
More on Cholestasis |
| Overview: Cholestasis |
| Differential Diagnoses & Workup: Cholestasis |
 Treatment & Medication: Cholestasis |
| Follow-up: Cholestasis |
| Multimedia: Cholestasis |
| References |
| Further Reading |
| « Previous Page | Next Page » |
References
Poddar U, Thapa BR, Das A, Bhattacharya A, Rao KN, Singh K. Neonatal cholestasis: differentiation of biliary atresia from neonatal hepatitis in a developing country. Acta Paediatr. May 13 2009;[Medline].
Strople J, Lovell G, Heubi J. Prevalence of Subclinical Vitamin K Deficiency in Cholestatic Liver Disease. J Pediatr Gastroenterol Nutr. Jun 3 2009;[Medline].
Hutchin T, Preece MA, Hendriksz C, et al. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) as a cause of liver disease in infants in the UK. J Inherit Metab Dis. Jun 11 2009;[Medline].
Mathias A, Wax JR, Pinette MG, Cartin A, Blackstone J. Progressive familial intrahepatic cholestasis complicating pregnancy. J Matern Fetal Neonatal Med. Jun 1 2009;1-3. [Medline].
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[Guideline] Moyer V, Freese DK, Whitington PF, et al. Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. J Pediatr Gastroenterol Nutr. Aug 2004;39(2):115-28. [Medline]. [Full Text].
[Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. Jun 2005;41(6):1407-32. [Medline]. [Full Text].
Balistreri WF. Neonatal cholestasis. J Pediatr. Feb 1985;106(2):171-84. [Medline].
Elferink RP, Groen AK. The mechanism of biliary lipid secretion and its defects. Gastroenterol Clin North Am. Mar 1999;28(1):59-74, vi. [Medline].
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Kaufman SS, Murray ND, Wood RP. Nutritional support for the infant with extrahepatic biliary atresia. J Pediatr. May 1987;110(5):679-86. [Medline].
Oude Elferink RP, Paulusma CC, Groen AK. Hepatocanalicular transport defects: pathophysiologic mechanisms of rare diseases. Gastroenterology. Mar 2006;130(3):908-25. [Medline].
Sabesin SM. Cholestatic lipoproteins--their pathogenesis and significance. Gastroenterology. Sep 1982;83(3):704-9. [Medline].
Suchy FJ. Approach to the infant with cholestasis. In: Liver Disease in Children. 1st ed. St. Louis, Mo:. Mosby;1994:349-355.
Trauner M, Meier PJ, Boyer JL. Molecular pathogenesis of cholestasis. N Engl J Med. Oct 22 1998;339(17):1217-27. [Medline].
Whitington PF. Chronic cholestasis of infancy. Pediatr Clin North Am. Feb 1996;43(1):1-26. [Medline].
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].
Further Reading
- Relevant clinical guidelines include the following:
- Relevant clinical trials include the following:
- Related eMedicine topics include the following:
- Progressive Familial Intrahepatic Cholestasis
- Primary Sclerosing Cholangitis (Gastroenterology)
- Primary Sclerosing Cholangitis (Pediatrics: General Medicine)
- Biliary Atresia
- Biliary Obstruction
Keywords
cholestasis, reduced bile formation, reduced bile flow, bile duct obstruction, cholestatic disorders, Dubin-Johnson syndrome, Rotor syndrome, Alagille syndrome, hyperchloremia, gram-negative sepsis, heart failure, metabolic disease, pruritus, itching, scratching, hyperlipidemia, xanthomas, xanthoma, failure to thrive, cholestatic liver disease, vitamin E deficiency, vitamin D deficiency, osteomalacia, rickets, biliary atresia, steatorrhea, scleral icterus, cutaneous jaundice, choledochal cyst, choledochal cyst, cholelithiasis, primary sclerosing cholangitis, hepatitis A, hepatitis B, hepatitis C, progressive familial intrahepatic cholestasis, treatment, diagnosis
