Primary sclerosing cholangitis

Primary sclerosing cholangitis
Classification and external resources
Cholangiogram of primary sclerosing cholangitis.
ICD-10	K83.0
ICD-9	576.1
OMIM	613806
DiseasesDB	10643
MedlinePlus	000285
eMedicine	med/3556
MeSH	D015209

Primary sclerosing cholangitis (PSC) is a disease of the bile ducts that causes inflammation and subsequent obstruction of bile ducts both at an intrahepatic (inside the liver) and extrahepatic (outside the liver) level. The inflammation impedes the flow of bile to the gut, which can ultimately lead to cirrhosis of the liver, liver failure and liver cancer. The underlying cause of the inflammation is believed to be autoimmunity;^[1] and more than 80% of those with PSC have ulcerative colitis.^[2] The definitive treatment is liver transplantation.

Signs and symptoms

PSC is characterized by recurrent episodes of cholangitis (inflammation of the bile ducts), with progressive biliary scarring and obstruction.

• Chronic fatigue (a non-specific symptom often present in liver disease)
• Severe jaundice with intense itching/ pruritus
• Malabsorption (especially of fat) and steatorrhea (fatty stool) due to biliary obstruction, leading to decreased levels of the fat-soluble vitamins, A, D, E and K.
• Signs of cirrhosis
• Hepatomegaly (enlarged liver)
• Portal hypertension
• Ascending cholangitis, or infection of the bile duct.
• Dark urine due to excess conjugated bilirubin, which is water soluble, being excreted by the kidneys
• Hepatic encephalopathy (confusion caused by liver dysfunction)

Diagnosis

The diagnosis is by imaging of the bile duct, usually in the setting of endoscopic retrograde cholangiopancreatography (ERCP), which shows "beading" (both strictures and dilation) of the intrahepatic and extrahepatic bile ducts. Another option is magnetic resonance cholangiopancreatography (MRCP), where magnetic resonance imaging is used to visualise the biliary tract.

Most patients with PSC have evidence of autoantibodies. Approximately 80% of patients have perinuclear anti-neutrophil cytoplasmic antibodies; however, this finding is not specific for PSC. Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients and, likewise, are not specific for the disease.^[1]

Other tests often done are a full blood count, liver enzymes, bilirubin levels (usually grossly elevated), renal function, electrolytes. Fecal fat determination is occasionally ordered when the symptoms of malabsorption are prominent.

The differential diagnosis can include primary biliary cirrhosis, drug induced cholestasis, cholangiocarcinoma, and HIV-associated cholangiopathy.

Etiology

The cause of PSC is unknown, although it is thought to be an autoimmune disorder. There is an increased prevalence of HLA alleles A1, B8, and DR3 in primary sclerosing cholangitis.^[1]

Pathophysiology

Inflammation damages bile ducts both inside and outside of the liver. The resulting scarring of the bile ducts blocks the flow of bile, causing cholestasis. Bile stasis and back-pressure induces proliferation of epithelial cells and focal destruction of the liver parenchyma, forming bile lakes. Chronic biliary obstruction causes portal tract fibrosis and ultimately biliary cirrhosis and liver failure.^[3]
Bile assists in the enteric breakdown and absorption of fat; the absence of bile leads to fat malabsorption and deficiencies of fat-soluble vitamins (A, D, E, K).^{[citation needed]}

Epidemiology

There is a 2:1 male-to-female predilection of primary sclerosing cholangitis.^[3] The disease normally starts from age 20 to 30, though may begin in childhood. PSC progresses slowly, so the disease can be active for a long time before it is noticed or diagnosed. There is relatively little data on the prevalence and incidence of primary sclerosing cholangitis, with studies in different countries showing annual incidence of 0.068–1.3 per 100,000 people and prevalence 0.22–8.5 per 100,000; given that PSC is closely linked with ulcerative colitis, it is likely that the risk is higher in populations where UC is more common.^[4]

Related diseases

Primary sclerosing cholangitis is associated with cholangiocarcinoma, a cancer of the biliary tree, and the lifetime risk for PSC sufferers is 10-15%. Screening for cholangiocarcinoma in patients with primary sclerosing cholangitis is encouraged, but there is no general consensus on the modality and interval of choice.^{[citation needed]}

Colon cancer is also associated with PSC.^{[citation needed]}

PSC has a significant association with ulcerative colitis, an inflammatory bowel disease primarily affecting the large intestine. As many as 5% of patients with ulcerative colitis may progress to develop primary sclerosing cholangitis ^[5] and approximately 70% of people with primary sclerosing cholangitis have ulcerative colitis.^[3]

Therapy

Standard treatment includes ursodiol, a bile acid naturally produced by the liver, which has been shown to lower elevated liver enzyme numbers in people with PSC, but has not improved liver- or overall survival.^[6] Treatment also includes medication to relieve itching (antipruritics), bile acid sequestrants (cholestyramine), antibiotics to treat infections, and vitamin supplements, as people with PSC are often deficient in vitamin A, vitamin D, vitamin E and vitamin K.

In some cases, ERCP, which may involve stenting of the common bile duct, may be necessary in order to open major blockages (dominant strictures).^{[citation needed]}

Liver transplantation is the only proven long-term treatment of PSC. Indications for transplantation include recurrent bacterial cholangitis, jaundice refractory to medical and endoscopic treatment, decompensated cirrhosis and complications of portal hypertension. In one series, 1, 2, and 5 year survival following liver transplantation for PSC was 90%, 86% and 85% respectively.^[1]

Prognosis

A German study in 2007 estimated the average survival time from time of diagnosis to be approximately 25 years, and the median time until either death or liver transplantation to be approximately 10 years.^[7]

See also

• Progressive familial intrahepatic cholestasis
• Walter Payton (died of primary sclerosing cholangitis)
• Chris LeDoux (professional rodeo rider and country musician with PSC who died of cholangiocarcinoma)
• Chris Klug (professional snowboarder with PSC who had liver transplant)

References

External links

• PSC Partners: Patient organization with additional information
• PSC Support : UK based Patient organization with additional information and discussion forum
• Additional Literature about PSC
• Information from The Morgan Foundation for the Study of PSC