eMedicine Specialties > Gastroenterology > Biliary

Primary Sclerosing Cholangitis

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

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.

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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  33. 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].

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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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