eMedicine Specialties > Gastroenterology > Biliary
Primary Sclerosing Cholangitis
Updated: Aug 28, 2009
Introduction
Background
Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by cholestasis with inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. The condition may lead to cirrhosis of the liver with portal hypertension. PSC has been reported more frequently since the development of endoscopic retrograde cholangiopancreatography (ERCP); until 1970, fewer than 100 patients with PSC had been reported. It is the fourth leading indication for liver transplantation in adults.
Pathophysiology
The etiology of this disease remains unknown, but a variety of factors are thought to be involved. An autoimmune mechanism is suggested, since approximately 75-90% of patients with PSC have inflammatory bowel disease (IBD). However, only approximately 4% of patients with IBD have or develop PSC. A marked increase in serum autoantibody levels occurs in patients with PSC as well, with antineutrophil cytoplasmic antibodies (ANCA) in 87%, anticardiolipin (aCL) antibodies in 66%, and antinuclear antibodies (ANA) in 53%.
In biliary ducts, an inflammatory response to chronic or recurrent bacterial infection in the portal circulation and from exposure to toxic bile acids has been postulated. A genetic predisposition has been suggested, because these patients have an increased prevalence of HLA-B8, HLA-DR3, and HLA-Drw52a. Ischemic damage to the biliary tree has also been postulated, since surgical trauma to the biliary tract can cause similar damage and because of the high number of patients with PSC who are ANCA–positive as observed in other vasculitides. Therefore, the most plausible concept of the pathogenesis of PSC involves the exposure of genetically predisposed individuals to an environmental antigen that subsequently elicits an aberrant immune response, leading to development of the disease.
Frequency
United States
In the United States, the prevalence rate of PSC as such is not known. Inferences are drawn based on the strong relationship with IBD. Prevalence is estimated at 6.3 cases per 100,000 population.
International
Western Europe is thought to have approximately the same prevalence rate as the United States, though Scandinavian countries report a somewhat higher rate. In many developing countries with limited access to advanced health care, the prevalence of PSC is probably underestimated, since the diagnosis cannot be confirmed without ERCP. The association of PSC with IBD may vary; for instance, in Japan, only 23% of patients with PSC have IBD.1
Mortality/Morbidity
PSC is generally a progressive disease that eventually culminates in portal hypertension and cirrhosis with complications. The median length of survival from diagnosis to death is approximately 12 years. Liver transplantation is the only treatment modality that appears to change the prognosis.
Race
A survey of the literature does not reveal a racial bias for PSC, but studies on this aspect of the disease are rather limited. Based on the epidemiological data available for IBD, the Jewish population might be expected to have a 2- to 4-fold higher prevalence, followed by (in descending order of frequency) whites, African Americans, Hispanics, and Asians.
Sex
Approximately 70% of patients with PSC are men with a mean age of diagnosis around 40 years. Patients with PSC but without IBD are more likely to be women and to be older at diagnosis.
Age
The mean age of diagnosis is 39 years. Diagnosis is usually made in symptomatic patients. A person may have the disease but be asymptomatic.
Clinical
History
Approximately 75-90% of patients have IBD. Of these, 87% have ulcerative colitis and 13% have Crohn colitis; however, the course of IBD is not related to PSC. Most patients are male and are diagnosed at a mean age of approximately 40 years.2
Symptoms upon initial presentation consist of fatigue, jaundice, pruritus, and right upper quadrant pain. The clinical course varies a great deal. Symptoms may remit and then recur spontaneously. Occasionally, patients with PSC may have an acute hepatitis-like presentation. Recurrent febrile episodes of bacterial cholangitis occur in 10-15% of patients during the course of PSC. Pancreatic duct involvement in PSC is uncommon, and pancreatic exocrine insufficiency is not correlated when ductal abnormalities are noted.
Patients with asymptomatic PSC comprise 20-40% of the cohort in some large studies. This high percentage is thought to be attributable to the practices of screening patients with ulcerative colitis for elevated alkaline phosphatase levels and performing ERCP in them. Cirrhosis, portal hypertension, and liver failure occur in progressive disease, with symptoms consistent with these entities, including variceal bleeding, ascites, and hepatic encephalopathy. The risk for cholangiocarcinoma is increased significantly in patients with PSC.3,4
The median length of survival from diagnosis to death or liver transplantation is 10-15 years. Patients who were symptomatic at diagnosis have a shorter survival time compared to those who were asymptomatic.
Physical
Physical examination results are significant for jaundice, weight loss, and, occasionally, pruritic skin marks. Hepatomegaly is common, and splenomegaly is present in up to one third of patients with PSC. As the disease progresses, signs of liver failure, including spider angiomata, ascites, and muscle atrophy, become apparent.
Causes
As previously noted, the exact cause of PSC remains unknown. The etiology is thought to be multifactorial, including genetic predisposition, exposure to an environmental antigen, and subsequent aberrant immunological response to that stimulus.
Differential Diagnoses
| Abdominal Vascular Injuries | Biliary Trauma |
| Acalculous Cholecystitis | Cholangiocarcinoma |
| Autoimmune Hepatitis | Cholangitis |
| Bile Duct Strictures | Choledocholithiasis |
| Bile Duct Tumors | Papillary Tumors |
| Biliary Obstruction | Primary Biliary Cirrhosis |
Other Problems to Be Considered
Other entities in the differential diagnoses include congenital diseases (eg, Caroli disease, choledochal cysts) and secondary cholangiopathy as observed in patients with collagen vascular diseases (eg, systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis) and in those with infiltrative diseases (eg, mediastinal fibrosis, Riedel thyroiditis, eosinophilic cholangitis, histiocytosis X). Infectious causes from parasitic, fungal, viral, or bacterial infections, or from recurrent cholangitis itself, especially in patients who are immunocompromised, can cause multifocal liver abscesses that lead to a PSC-like appearance of the bile duct.
Workup
Laboratory Studies
- Liver function tests: These tests are the most valuable in the laboratory workup.
- Serum alkaline phosphatase dominates the profile, which is cholestatic in nature. Alkaline phosphatase levels are usually 3-5 times reference range values. Alkaline phosphatase can be divided into its various fractions to ascertain its origin from liver disease as opposed to bone disease. Serum gamma-glutamyl transpeptidase levels mirror this rise and can help differentiate cholestasis from bone disease. Some patients with hypothyroidism, hypophosphatemia, or zinc or magnesium deficiency may have normal alkaline phosphatase levels.
- Serum aminotransferase levels are increased but not markedly so. Serum bilirubin levels, with the conjugated component, are usually increased, but fluctuations in the level can occur. Serum albumin levels decrease later in the course of the disease, and the presence of hypoalbuminemia earlier in the disease may indicate active IBD.
- Hypergammaglobulinemia is present in 30% of patients, and 50% have increased immunoglobulin (IgM) levels. p-ANCA, aCL antibodies, and ANA are present in up to 84%, 66%, and 53% of patients, respectively.
Imaging Studies
- ERCP is considered the criterion standard for confirming a diagnosis of PSC. Radiological features in ERCP include multiple strictures and dilations of the intrahepatic and extrahepatic biliary ducts.
- Transhepatic cholangiography is performed when ERCP is unsuccessful.
- Because it is noninvasive, magnetic resonance cholangiopancreatography (MRCP) is rapidly developing as the preferred study to evaluate the bile ducts. As image quality continues to improve, MRCP may become the criterion standard.
Procedures
- Liver biopsy is rarely diagnostic of PSC, although it does help determine both the stage and the prognosis of the disease.
Histologic Findings
A variety of histopathologic liver changes are noted in patients with PSC. The most common characteristic feature is onionskin fibrosis, which describes the appearance of periductal concentric fibrosis around the interlobular and septal bile ducts. This is present in only half of all biopsy specimens from patients with otherwise typical PSC, whereas concentric fibrosis with obliteration of the small ducts (obliterative fibrous cholangitis)—a virtually diagnostic histopathologic lesion—is found in fewer than 10% of biopsy specimens.
Periductal fibrosis may be accompanied by infiltrates of inflammatory cells. Piecemeal necrosis, as occurs in patients with chronic hepatitis, may be observed as well.
Staging
In 1981, Ludwig and associates described 4 stages of PSC, as follows:
- Stage 1 - Portal hepatitis, degeneration of bile ducts with inflammatory cell infiltrate
- Stage 2 - Extension of disease to periportal area with prominent bile ductopenia
- Stage 3 - Septal fibrosis and necrosis
- Stage 4 - Frank cirrhosis
The most characteristic histological feature of onionskin fibrosis, which consists of concentric fibrosis around the septal bile ducts, is noted in only approximately 10% of biopsy specimens.
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.
Dosing
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
Interactions
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
Contraindications
Documented hypersensitivity; low levels of TPMT
Precautions
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.
Dosing
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
Interactions
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
Contraindications
Documented hypersensitivity; uncontrolled hypertension or malignancies; concomitant administration with PUVA or UV-B radiation in psoriasis owing to possible increased risk of cancer
Precautions
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.
Dosing
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
Interactions
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
Contraindications
Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective-tissue infections; fungal or tubercular skin infections; GI bleeding or ulceration
Precautions
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.
Dosing
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
Interactions
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
Contraindications
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
Precautions
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.
Dosing
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
Interactions
Increases effects of immunosuppressants, phenylbutazone, and antimalarials; decreases digoxin effects; effects may decrease with coadministration of zinc salts, antacids, and iron
Contraindications
Documented hypersensitivity; renal insufficiency; previous penicillamine-related aplastic anemia
Precautions
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.
Dosing
Adult
8-10 mg/kg PO divided bid/tid
Pediatric
Not established
Interactions
Decreased effect with aluminum-containing antacids, cholestyramine, colestipol, clofibrate, and oral contraceptives
Contraindications
Documented hypersensitivity; unremitting acute cholecystitis; cholangitis; biliary obstruction; calcified cholesterol stones; radiopaque stones; bile pigment stones, gallstone pancreatitis, or biliary-gastrointestinal fistula
Precautions
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.
Dosing
Adult
4 g PO qd/bid; not to exceed 24 g/d or 6 doses/d
Pediatric
240 mg/kg PO divided tid
Interactions
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
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Caution in constipation and phenylketonuria
Follow-up
Further Inpatient Care
- Further inpatient care is dictated by the admitting diagnosis and complications and may involve any or all of the previously discussed treatment options.
Further Outpatient Care
- Further outpatient care is dictated by the stage and degree of progression of the disease. It involves care by a gastroenterologist, who must monitor the patient's condition with frequent laboratory tests and maintain vigilance for the many complications of PSC. Suitability for liver transplantation should be determined expeditiously and, if appropriate, offered to the patient.
Deterrence/Prevention
- PSC is a progressive disease, and no preventive strategies have been proven effective. Stopping smoking and/or drinking may decrease or delay the chances of developing cholangiocarcinoma.
Complications
- Chronic cholestasis leads to steatorrhea, fat-soluble vitamin (A, D, E, and K) deficiency, metabolic bone disease with osteoporosis, and calorie loss with resultant weight loss.
- Cholangitis and cholelithiasis occur more frequently in patients with PSC.
- Cholangiocarcinoma reportedly occurs in association with PSC in 6-30% of patients and in up to 30-40% of patients with PSC on autopsy. The development of cholangiocarcinoma remains unpredictable in any given patient, and no reliable serological tumor markers have been identified.
- Secondary biliary cirrhosis due to chronic cholestasis occurs in patients with PSC. Portal hypertension with variceal bleeding, ascites, and liver failure then ensue.
- Dominant biliary strictures can be identified in about 20% of patients with PSC and must be differentiated from cholangiocarcinoma. Strictures cause cholestasis with jaundice and pruritus and may also result in cholangitis.
- The risk of colon cancer is increased for patients with both ulcerative colitis and PSC versus those with only ulcerative colitis.
Prognosis
- PSC is a progressive disorder that ultimately leads to hepatic failure. Median survival time without liver transplantation is about 12 years. Survival prospects are more dismal for those who are symptomatic at diagnosis. The following variables influence prognosis:
- Revised Mayo Clinic model
- Age
- Serum bilirubin, albumin, and aspartate aminotransferase levels
- Variceal bleeding history
- Child-Turcotte-Pugh scale
- Grade of encephalopathy
- Presence or absence of ascites
- Serum albumin level
- Prothrombin time
- Bilirubin level
- Revised Mayo Clinic model
Patient Education
- Educate patients regarding the natural course of the disease, expected complications, and treatment strategies, including liver transplantation.
Miscellaneous
Medicolegal Pitfalls
- Failure to conscientiously monitor and treat complications, including those caused by nutritional deficits (eg, night blindness, osteoporosis with resultant fractures)
- Failure to recognize that worsening jaundice, pruritus, or weight loss may indicate development of a stricture or cholangiocarcinoma
- Failure to perform colonoscopy or flexible sigmoidoscopy in patients with PSC without a history of IBD
- Failure to conduct periodic colonoscopic surveillance of patients with PSC and ulcerative colitis to exclude colonic neoplasia
- Failure to monitor for toxicity in patients taking certain immunosuppressant drugs
References
Okada H, Mizuno M, Yamamoto K, Tsuji T. Primary sclerosing cholangitis in Japanese patients: association with inflammatory bowel disease. Acta Med Okayama. Oct 1996;50(5):227-35. [Medline].
Ananthakrishnan AN, Beaulieu DB, Ulitsky A, Zadvornova Y, Skaros S, Johnson K, et al. Does primary sclerosing cholangitis impact quality of life in patients with inflammatory bowel disease?. Inflamm Bowel Dis. Jul 27 2009;[Medline].
Abbas G, Lindor KD. Cholangiocarcinoma in primary sclerosing cholangitis. J Gastrointest Cancer. Aug 25 2009;epub ahead of print. [Medline].
Jesudian AB, Jacobson IM. Screening and diagnosis of cholangiocarcinoma in patients with primary sclerosing cholangitis. Rev Gastroenterol Disord. Spring 2009;9(2):E41-7. [Medline].
Lindor KD, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, et al. High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis. Hepatology. May 20 2009;[Medline].
Shi J, Li Z, Zeng X, Lin Y, Xie WF. Ursodeoxycholic acid in primary sclerosing cholangitis: meta-analysis of randomized controlled trials. Hepatol Res. May 7 2009;[Medline].
Angulo P, Peter JB, Gershwin ME, et al. Serum autoantibodies in patients with primary sclerosing cholangitis. J Hepatol. Feb 2000;32(2):182-7. [Medline].
Borkje B, Vetvik K, Odegaard S, et al. Chronic pancreatitis in patients with sclerosing cholangitis and ulcerative colitis. Scand J Gastroenterol. May 1985;20(4):539-42. [Medline].
Broome U, Lofberg R, Veress B, Eriksson LS. Primary sclerosing cholangitis and ulcerative colitis: evidence for increased neoplastic potential. Hepatology. Nov 1995;22(5):1404-8. [Medline].
Cangemi JR, Wiesner RH, Beaver SJ, et al. Effect of proctocolectomy for chronic ulcerative colitis on the natural history of primary sclerosing cholangitis. Gastroenterology. Mar 1989;96(3):790-4. [Medline].
Chapman RW, Arborgh BA, Rhodes JM, et al. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut. Oct 1980;21(10):870-7. [Medline].
Eckhauser FE, Colleti LM, Knol JA. The changing role of surgery for sclerosing cholangitis. Dig Dis. May-Jun 1996;14(3):180-91. [Medline].
Farrant JM, Hayllar KM, Wilkinson ML, et al. Natural history and prognostic variables in primary sclerosing cholangitis. Gastroenterology. Jun 1991;100(6):1710-7. [Medline].
Graziadei IW, Wiesner RH, Batts KP, et al. Recurrence of primary sclerosing cholangitis following liver transplantation. Hepatology. Apr 1999;29(4):1050-6. [Medline].
Graziadei IW, Wiesner RH, Marotta PJ, et al. Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis. Hepatology. Nov 1999;30(5):1121-7. [Medline].
Helzberg JH, Petersen JM, Boyer JL. Improved survival with primary sclerosing cholangitis. A review of clinicopathologic features and comparison of symptomatic and asymptomatic patients. Gastroenterology. Jun 1987;92(6):1869-75. [Medline].
Johnson GK, Geenen JE, Venu RP, et al. Endoscopic treatment of biliary tract strictures in sclerosing cholangitis: a larger series and recommendations for treatment. Gastrointest Endosc. Jan-Feb 1991;37(1):38-43. [Medline].
Kim WR, Therneau TM, Wiesner RH, et al. A revised natural history model for primary sclerosing cholangitis. Mayo Clin Proc. Jul 2000;75(7):688-94. [Medline].
Lee YM, Kaplan MM. Management of primary sclerosing cholangitis. Am J Gastroenterol. Mar 2002;97(3):528-34. [Medline].
Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. Apr 6 1995;332(14):924-33. [Medline].
Ludwig J, Barham SS, LaRusso NF, et al. Morphologic features of chronic hepatitis associated with primary sclerosing cholangitis and chronic ulcerative colitis. Hepatology. Nov-Dec 1981;1(6):632-40. [Medline].
Lundqvist K, Broome U. Differences in colonic disease activity in patients with ulcerative colitis with and without primary sclerosing cholangitis: a case control study. Dis Colon Rectum. Apr 1997;40(4):451-6. [Medline].
MacCarty RL, LaRusso NF, Wiesner RH, Ludwig J. Primary sclerosing cholangitis: findings on cholangiography and pancreatography. Radiology. Oct 1983;149(1):39-44. [Medline].
Olsson R, Danielsson A, Jarnerot G, et al. Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis. Gastroenterology. May 1991;100(5 Pt 1):1319-23. [Medline].
Rabinovitz M, Gavaler JS, Schade RR, et al. Does primary sclerosing cholangitis occurring in association with inflammatory bowel disease differ from that occurring in the absence of inflammatory bowel disease? A study of sixty-six subjects. Hepatology. Jan 1990;11(1):7-11. [Medline].
Rosen CB, Nagorney DM, Wiesner RH, et al. Cholangiocarcinoma complicating primary sclerosing cholangitis. Ann Surg. Jan 1991;213(1):21-5. [Medline].
Schrumpf E, Elgjo K, Fausa O, et al. Sclerosing cholangitis in ulcerative colitis. Scand J Gastroenterol. 1980;15(6):689-97. [Medline].
Shepherd HA, Selby WS, Chapman RW, et al. Ulcerative colitis and persistent liver dysfunction. Q J Med. Autumn 1983;52(208):503-13. [Medline].
Shetty K, Rybicki L, Carey WD. The Child-Pugh classification as a prognostic indicator for survival in primary sclerosing cholangitis. Hepatology. May 1997;25(5):1049-53. [Medline].
Taylor BV, Wijdicks EF, Poterucha JJ, Weisner RH. Chronic inflammatory demyelinating polyneuropathy complicating liver transplantation. Ann Neurol. Nov 1995;38(5):828-31. [Medline].
Terblanche J, Allison HF, Northover JM. An ischemic basis for biliary strictures. Surgery. Jul 1983;94(1):52-7. [Medline].
UNOS Update. Primary liver disease of liver transplant recipients, 1991 and 1992. 1993;9(8):27-9.
van Milligen de Wit AW, van Deventer SJ, Tytgat GN. Immunogenetic aspects of primary sclerosing cholangitis: implications for therapeutic strategies. Am J Gastroenterol. Jun 1995;90(6):893-900. [Medline].
Wiesner RH. Current concepts in primary sclerosing cholangitis. Mayo Clin Proc. Oct 1994;69(10):969-82. [Medline].
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
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.
Related eMedicine Topics
- Cirrhosis
- Cholangitis [Emergency Medicine section]
- Cholangitis, Primary Sclerosing [in the Radiology section]
- Cholangitis, Recurrent Pyogenic [in the Radiology section]
- Cholelithiasis
- Portal Hypertension
- Primary Biliary Cirrhosis
- Recurrent Pyogenic Cholangitis
- Compare Conventional Colonosocpy to Endoscopic AFI, NBI for Dysplasia Detection for Ulcerative Colitis & Cholangitis
- Cholangioscopy Using Narrow Band Imaging (NBI) in Patients With Primary Sclerosing Cholangitis (PSC) Undergoing Endoscopic Retrograde Cholangiopancreatogram (ERCP)
- Erlotinib for Chemoprevention in Trisomy 7 Positive Primary Sclerosing Cholangitis (PSC)
- Laparoendoscopic Rendez Vous Versus Standard Two Stage Approach for the Management of Cholelithiasis/Choledocholithiasis
- Use of Probiotics to Prevent Cholangitis in Children With Biliary Atresia After the Kasai Portoenterostomy
- ACR Appropriateness Criteria® acute abdominal pain and fever or suspected abdominal abscess. American College of Radiology - Medical Specialty Society. 1996 (revised 2006). 7 pages. NGC:005138
- ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2005 Jul. 8 pages. NGC:00448
- Quality indicators for endoscopic retrograde cholangiopancreatography. American College of Gastroenterology - Medical Specialty Society; American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2006 Apr. 6 pages. NGC:004967
© 1994-
by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)