eMedicine Specialties > Gastroenterology > Biliary

Primary Sclerosing Cholangitis: Treatment & Medication

Author: Vikas Khurana, MD, FACP, FACG, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Graduate Hospital, Gastroenterology Associates, PC
Coauthor(s): Tejinder Singh, MD, Lead Physician, Section of Emergency Services, Overton Brooks Veterans Affairs Medical Center; Praveen K Roy, MD, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group
Contributor Information and Disclosures

Updated: Aug 28, 2009

Treatment

Medical Care

PSC is a chronic progressive disease with no curative medical therapy. The goals of medical management are to treat the symptoms and to prevent or treat the known complications. Liver transplantation is the only effective therapy and is indicated in end-stage liver disease.

Surgical Care

Surgical therapy includes liver transplantation, proctocolectomy (for patients with ulcerative colitis), and biliary reconstructive procedures. Note that proctocolectomy in patients with both PSC and ulcerative colitis has no effect on the course of PSC.

Indications for liver transplantation include variceal bleed or portal gastropathy, intractable ascites, recurrent cholangitis, progressive muscle wasting, and hepatic encephalopathy. Centers are reporting survival rates of 93.7%, 92.2%, 86.4%, and 69.8% at 1, 2, 5, and 10 years, respectively. However, PSC recurs in 15-20% of patients after transplantation.

Consultations

A gastroenterologist must be consulted. When needed, surgical consultation should be initiated by the gastroenterologist and when liver transplantation is offered. An endocrinologist may be consulted for management of bone disease. Endoscopic dilation of dominant strictures, with or without stenting, has been shown to alleviate cholestasis and to improve laboratory test results; however, it is not currently believed to affect disease progression. Ruling out malignancy in these strictures is difficult.

Diet

Patients with steatorrhea are encouraged to include medium-chain triglycerides in their diet. Fat-soluble vitamin deficiency correction should be attempted by supplementation. Oral supplementation is necessary if associated pancreatic enzyme deficiency is present. Calcium supplementation for bone disease may also be needed.

Activity

Physical activity should not be restricted; however, in patients with osteoporosis, the possibility of fractures should temper the type of activity allowed.

Medication

No medical therapy has been proven effective for PSC. Therapy is aimed at treating symptoms and managing complications. Liver transplantation is the only therapy that can alter the eventual outcome. Immunosuppressants, chelators, and steroids are used in an attempt to control the disease process but have not shown significant benefit.

Ursodeoxycholic acid improves the liver function profile in some patients and, in conjunction with endoscopic dilation, has shown a survival benefit in some studies. Trials using ursodeoxycholic acid in higher doses and earlier in the disease course are ongoing.

Two recent studies investigated high-does ursodeoxycholic acid in the treatment of PSC demonstrated similar findings.5,6  A long-term, randomized, double-blind controlled trial by Lindor et al of 150 adult patients with PSC in which 28-30 mg/kg/day of ursodeoxycholic acid was compared with placebo used primary outcome measures of development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death.5 Before termination of the study after 6 years "due to futility," liver biopsy and cholangiography were performed both before randomization and after 5 years. Findings during therapy included a greater decrease in serum liver test results in the group treated with ursodeoxycholic acid than in the placebo group (P <0.01), but there was no association with decreased endpoints.5  

By the study's end, 39% (n = 30) of the patients in the ursodeoxycholic acid group achieved one of the preestablished clinical endpoints, compared with 26% (n = 19) of those in the placebo group.5 However, in addition to a higher incidence of serious adverse events, the risk of a primary endpoint was 2.3-fold greater for the ursodeoxycholic acid-treated group than those in the placebo group (P <0.01) and 2.1-fold greater for death, transplantation, or minimal listing criteria (P = 0.038).5

The study by Shi et al also examined the safety and efficacy of ursodeoxycholic acid in the treatment of PSC.6 the investigators performed a meta-analysis of all randomized controlled trials that compared ursodeoxycholic acid with placebo or no treatment and found 8 studies consisting of 465 patients. Findings included ursodeoxycholic acid's positive effects in improving liver biochemistry but none on pruritus and fatigue, or the incidence of death, liver transplantation, and death and/or liver transplantation.6 However, there were trends in histologic and cholangiographic improvement.

Immunosuppressant agents

With the possibility of an autoimmune pathogenesis for PSC, immunosuppressive therapy has been used in treatment of PSC. Results of therapeutic trials, however, have been disappointing.


Azathioprine (Imuran)

Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Adult

1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg PO q4wk until response, or when dose reaches 2.5 mg/kg/d

Pediatric

Initial dose: 2-5 mg/kg PO/IV
Maintenance dose: 1-2 mg/kg/d PO/IV

Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Documented hypersensitivity; low levels of TPMT

Pregnancy

D - Unsafe in pregnancy

Precautions

Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy and follow liver, renal, and hematologic functions; pancreatitis is rarely associated


Cyclosporine (Sandimmune, Neoral)

Cyclic polypeptide that suppresses some humoral immunity and, to a greater extent, cell-mediated immune reactions, such as delayed hypersensitivity, allograft rejection, experimental allergic encephalomyelitis, and graft vs host disease for a variety of organs. For both children and adults, base dosing on ideal body weight.

Adult

Initial dose: 14-18 mg/kg PO 4-12 h before organ transplantation
Alternative initial dose: 5-6 mg/kg IV 4-12 h before organ transplantation
Maintenance dose: 5-15 mg/kg PO qd or divided bid
Alternative maintenance dose: 2-10 mg/kg/d IV divided q8-12h

Pediatric

Administer as in adults

Carbamazepine, phenytoin, isoniazid, rifampin, and phenobarbital may decrease concentrations; azithromycin, itraconazole, nicardipine, ketoconazole, fluconazole, erythromycin, verapamil, grapefruit juice, diltiazem, aminoglycosides, acyclovir, amphotericin B, and clarithromycin may increase toxicity; acute renal failure, rhabdomyolysis, myositis, and myalgias increase when taken concurrently with lovastatin; methylprednisolone and cyclosporine mutually inhibit one another, resulting in increased plasma levels of each drug

Documented hypersensitivity; uncontrolled hypertension or malignancies; concomitant administration with PUVA or UV-B radiation in psoriasis owing to possible increased risk of cancer

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Frequently evaluate renal and liver functions by measuring BUN, serum creatinine, serum bilirubin, and liver enzymes; may increase risk of infection and lymphoma; reserve IV use for persons who cannot take PO


Prednisone (Orasone, Deltasone, Meticorten, Sterapred)

Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Adult

5-60 mg PO qd or divided bid/qid; taper over 2 wk as symptoms resolve

Pediatric

4-5 mg/m2/d PO; alternatively, 0.05-2 mg/kg PO divided bid/qid; taper over 2 wk as symptoms resolve

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective-tissue infections; fungal or tubercular skin infections; GI bleeding or ulceration

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use


Methotrexate (Folex PFS, Rheumatrex)

Antimetabolite used in the treatment of certain neoplastic diseases, severe psoriasis, and adult rheumatoid arthritis. Inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be used as carriers of single-carbon groups in the synthesis of purine nucleotides and thymidylate. Methotrexate therefore interferes with DNA synthesis, repair, and cellular replication.

Adult

7.5 mg PO qwk; alternatively, 2.5 mg PO q12h for 3 doses given qwk; in either schedule, dosages may be gradually adjusted to achieve optimal response; typically, not to exceed 20 mg total weekly dose

Pediatric

Recommended starting dose is 10 mg/m2 administered qwk, although doses up to 30 mg/m2/wk have reportedly been used in children, too few published data are available to allow assessment of how doses >20 mg/m2/wk might affect risk of serious toxicity in children

Oral aminoglycosides may decrease absorption and blood levels; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines

Documented hypersensitivity; pregnancy and breastfeeding mothers; alcoholism, alcoholic liver disease, or other chronic liver disease; laboratory evidence of immunodeficiency syndromes, psoriasis, or rheumatoid arthritis; preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia, or significant anemia

Pregnancy

X - Contraindicated in pregnancy

Precautions

Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated MTX levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood cell counts occurs; fatal reactions reported when administered concurrently with NSAIDs

Chelating agents

Observation of increased serum, urinary, and hepatic copper concentrations in patients with PSC has prompted the use of penicillamine, which is a chelator.


Penicillamine (Cuprimine, Depen)

Chelating agent recommended for removal of excess copper in patients with Wilson disease. Depresses circulating IgM rheumatoid factor and T-cell, but not B-cell, activity.

Adult

125-250 mg/d PO initially; may increase dose at 1- to 3-mo intervals, not to exceed 1-1.5 g/d

Pediatric

3 mg/kg/d PO for 3 mo, then 6 mg/kg/d PO divided bid for 3 mo to maximum 10 mg/kg/d PO divided tid/qid

Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; effects may decrease with coadministration of zinc salts, antacids, and iron

Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia

Pregnancy

D - Unsafe in pregnancy

Precautions

Thrombocytopenia, agranulocytosis, and aplastic anemia may occur

Gallstone dissolution agents

Thought to remove toxic bile acids from the enterohepatic circulation and to offer protection to the bile duct from injury.


Ursodiol (Actigall)

Suppresses hepatic synthesis and secretion of cholesterol and inhibits intestinal absorption of cholesterol. May displace natural, toxic, and endogenous bile acids from enterohepatic circulation and provide a cytoprotective effect, which may lead to decrease cholestasis and improved liver functions.

Adult

8-10 mg/kg PO divided bid/tid

Pediatric

Not established

Decreased effect with aluminum-containing antacids, cholestyramine, colestipol, clofibrate, and oral contraceptives

Documented hypersensitivity; unremitting acute cholecystitis; cholangitis; biliary obstruction; calcified cholesterol stones; radiopaque stones; bile pigment stones, gallstone pancreatitis, or biliary-gastrointestinal fistula

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Caution in patients with a nonvisualizing gallbladder; lithocholic acid, a naturally occurring bile acid, may cause toxicity; measure SGOT (AST) and SGPT (ALT) at initiation of therapy and thereafter as clinically indicated

Antilipemic agents

Are thought to decrease pruritus by combining with bile acids in the intestine and by causing them to be excreted because of nonreabsorption.


Cholestyramine (Prevalite, Questran)

Forms a nonabsorbable complex with bile acids in the intestine, which, in turn, inhibits enterohepatic reuptake of intestinal bile salts. In patients with partial biliary obstruction, the reduction of serum bile acid levels by cholestyramine reduces excess bile acids deposited in dermal tissue, which decreases pruritus.

Adult

4 g PO qd/bid; not to exceed 24 g/d or 6 doses/d

Pediatric

240 mg/kg PO divided tid

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

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Caution in constipation and phenylketonuria

More on Primary Sclerosing Cholangitis

Overview: Primary Sclerosing Cholangitis
Differential Diagnoses & Workup: Primary Sclerosing Cholangitis
Treatment & Medication: Primary Sclerosing Cholangitis
Follow-up: Primary Sclerosing Cholangitis
References
Further Reading
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References

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Further Reading

Related eMedicine Topics

Clinical Trials
 National Guideline Clearinghouse

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Keywords

primary sclerosing cholangitis, PSC, sclerosis of the liver, chronic liver disease, biliary cirrhosis, chronic hepatic disease, cholestasis, intrahepatic bile ducts, extrahepatic bile ducts, liver cirrhosis, portal hypertension, liver transplantation, liver transplant, inflammatory bowel disease, IBD,

ulcerative colitis, Crohn colitis, Crohn disease, bacterial cholangitis, cholangiocarcinoma, hepatomegaly, splenomegaly, endoscopic retrograde cholangiopancreatography, ERCP, magnetic resonance cholangiopancreatography, MRCP

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Contributor Information and Disclosures

Author

Vikas Khurana, MD, FACP, FACG, Assistant Professor, Department of Medicine, Division of Gastroenterology and Hepatology, Graduate Hospital, Gastroenterology Associates, PC
Disclosure: Nothing to disclose.

Coauthor(s)

Tejinder Singh, MD, Lead Physician, Section of Emergency Services, Overton Brooks Veterans Affairs Medical Center
Disclosure: Nothing to disclose.

Praveen K Roy, MD, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group
Praveen K Roy, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and Canadian Association of Gastroenterology
Disclosure: Nothing to disclose.

Medical Editor

David Greenwald, MD, Fellowship Program Director, Associate Professor, Department of Medicine, Division of Gastroenterology, Montefiore Medical Center, Albert Einstein College of Medicine
David Greenwald, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Simmy Bank, MD, Chair, Professor, Department of Internal Medicine, Division of Gastroenterology, Long Island Jewish Hospital, Albert Einstein College of Medicine
Disclosure: Nothing to disclose.

CME Editor

Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.

 
 
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