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Primary Sclerosing Cholangitis

  • Author: Vikas Khurana, MD, FACP, FACG; Chief Editor: Julian Katz, MD  more...
 
Updated: Jan 03, 2016
 

Background

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by a progressive course of cholestasis with inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts.[1] The underlying cause of the inflammation is believed to be autoimmunity. The condition may lead to cirrhosis of the liver with portal hypertension.[1] (See Clinical.)

PSC is strongly associated with inflammatory bowel disease,[2, 3] mainly ulcerative colitis, and is often complicated by cholangiocarcinoma development. A higher risk of colorectal cancer has been described among ulcerative colitis patients with PSC.Surveillance for colorectal cancer should therefore be strongly recommended in PSC patients with ulcerative colitis.[2, 3, 4]

PSC has been reported more frequently since the development of endoscopic retrograde cholangiopancreatography (ERCP). Liver function tests are the most valuable in the laboratory workup, including serum alkaline phosphatase, serum aminotransferase, and hypergammaglobulinemia. (See Workup.)

Therapy is aimed at treating symptoms and managing complications. Immunosuppressants, chelators, and steroids are used in an attempt to control the disease process but have not shown significant benefit. Liver transplantation is the only therapy that can alter the eventual outcome. PSC is the fourth leading indication for liver transplantation in adults. (See Treatment and Medication.)

For more information, see the Medscape Reference articles Pediatric Primary Sclerosing Cholangitis and Primary Sclerosing Cholangitis Imaging.

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Pathophysiology and Etiology

The etiology of this disease remains unknown, but a variety of factors are thought to be involved.[1] The etiology is thought to be multifactorial, including genetic predisposition, exposure to an environmental antigen, and subsequent aberrant immunologic response to that stimulus. There is also an increased prevalence of HLA alleles A1, B8, and DR3 in PSC.[5, 6]

An autoimmune mechanism is suggested because approximately 75-90% of patients with primary sclerosing cholangitis (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%. It has been reported that PSC and IBD have overlapping yet distinct genetic architectures.[7]

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.[8] A genetic predisposition has been suggested because of an increased prevalence of HLA-B8, HLA-DR3, and HLA-Drw52a. Recently, genome-wide association studies performed in PSC have identified a number of genetic susceptibility loci. Subclassification of PSC patients according to their genetic predisposition may well constitute a valuable tool for future research in the subject.[9]

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.

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Epidemiology

In the United States, the prevalence of primary sclerosing cholangitis (PSC) is not known. Inferences have been drawn on the basis of the strong relationship with inflammatory bowel disease (IBD), which has a prevalence of 60-80% in western countries.[2]

The prevalence of PSC is estimated to be 6.3 cases per 100,000 population. Western Europe is thought to have approximately the same prevalence as in 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.[10] The disease normally starts at age 20-30 years, although it may begin in childhood. The disease may be active for a long time before it is noticed or diagnosed.

A survey of the literature has not revealed a racial bias for PSC, but studies on this aspect of the disease are rather limited. Based on the epidemiologic 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.

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.

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Prognosis

Primary sclerosing cholangitis (PSC) is generally a progressive disease that eventually culminates in portal hypertension, and cirrhosis with complications, and hepatic failure. 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. Survival prospects are more dismal for those who are symptomatic at diagnosis.

The revised Mayo Clinic model for survival probability in patients with PSC[11, 12] includes the following:

  • Age
  • Serum bilirubin, albumin, and aspartate aminotransferase levels
  • Variceal bleeding history

The Child-Turcotte-Pugh scale[13] for calculation of severity of disease includes the following:

  • Grade of encephalopathy
  • Presence or absence of ascites
  • Serum albumin level
  • Prothrombin time
  • Bilirubin level

A study by Rupp et al indicated that patients with PSC who reduce their alkaline phosphatase levels within the first year of having the condition have longer periods of liver transplantation – free survival, independent of the existence of dominant biliary strictures. The study involved 215 patients with PSC, some of whom were without strictures, some of whom presented with strictures, and some of whom developed strictures during the study. The amount and speed of alkaline phosphatase reduction were monitored, with previously published values for alkaline phosphatase decreases in patients with PSC also taken into account.[14]

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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)

Hisham Nazer, MB, BCh, FRCP, , DTM&H Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, University of Jordan Faculty of Medicine, Jordan

Hisham Nazer, MB, BCh, FRCP, , DTM&H is a member of the following medical societies: American Association for Physician Leadership, Royal College of Paediatrics and Child Health, Royal College of Surgeons in Ireland, Royal Society of Tropical Medicine and Hygiene, Royal College of Physicians and Surgeons of the United Kingdom

Disclosure: Nothing to disclose.

Praveen K Roy, MD, AGAF Chief of Gastroenterology, Presbyterian Hospital; Medical Director of Endoscopy, Presbyterian Medical Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute

Praveen K Roy, MD, AGAF is a member of the following medical societies: American Gastroenterological Association, American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Tejinder Singh, MD Lead Physician, Section of Emergency Services, Overton Brooks Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

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 & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

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.

David Greenwald, MD Associate Professor of Clinical Medicine, Fellowship Program Director, 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, American Society for Gastrointestinal Endoscopy, and New York Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

References
  1. Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG Clinical Guideline: Primary Sclerosing Cholangitis. Am J Gastroenterol. 2015 May. 110 (5):646-59; quiz 660. [Medline].

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Periductal onion skin fibrosis seen in primary sclerosing cholangitis.
Endoscopic retrograde cholangiopancreatography performed in a patient with abnormal liver function test results shows multiple intrahepatic bile duct strictures and beading.
Double-contrast barium enema (same patient as in the previous image) shows filiform polyps and an ahaustral colon resulting from ulcerative colitis.
Percutaneous transhepatic cholangiogram shows dilatation, stricturing, and beading of the intrahepatic bile ducts. Note the surgical clips from a previous cholecystectomy.
T-tube cholangiogram shows irregularity of the common bile duct, stricturing, beading, and dilatation of the intrahepatic bile ducts. Note a calculus in the termination of the left hepatic duct (arrow).
Magnetic resonance cholangiopancreatography shows a normal-sized common bile duct, but strictures of both the left and right ducts are noted as well as a dilated proximal left hepatic duct.
Technetium-99m iminodiacetic acid scan shows retention of the radionuclide proximal to strictures in the distribution of the left hepatic duct. Note the lack of filling of the gallbladder because of a previous cholecystectomy. Isotope has entered the small bowel.
 
 
 
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