Primary sclerosing cholangitis is a disease of the bile ducts that causes inflammation
and subsequent obstruction of bile ducts both inside and outside of the liver.
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; and more than
80% of those with PSC have ulcerative colitis.
The definitive treatment is a liver transplant.
Signs and symptoms PSC is characterized by recurrent episodes
of cholangitis, with progressive biliary scarring and obstruction.
Chronic fatigue Severe jaundice with intense itching/ pruritus
Malabsorption and steatorrhea due to biliary obstruction, leading to decreased levels of
the fat-soluble vitamins, A, D, E and K. Signs of cirrhosis
Hepatomegaly 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
Cause 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.
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.
Bile assists in the intestinal breakdown and absorption of fat; the absence of bile leads
to fat malabsorption and deficiencies of fat-soluble vitamins.
Diagnosis PSC is diagnosed by visualizing the bile duct
with imaging, usually in the setting of endoscopic retrograde cholangiopancreatography, which
shows "beading" of bile ducts inside and outside of the liver.
Another option is magnetic resonance cholangiopancreatography, where magnetic resonance imaging is used to
visualize the biliary tract.
Most people with PSC have evidence of autoantibodies.
Approximately 80% of people with PSC have perinuclear anti-neutrophil cytoplasmic antibodies;
however, this finding is not specific to those with the disease.
Antinuclear antibodies and anti-smooth muscle antibody are found in 20%-50% of PSC patients
and, likewise, are not specific for the disease.
Other tests often done are a full blood count, liver enzymes, bilirubin levels, kidney function,
and 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.
Management 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.
Treatment also includes medication to relieve itching, bile acid sequestrants, 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.
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.
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.
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%.
This represents a 160-fold greater risk of developing cholangiocarcinoma compared to
the general population.
Screening for cholangiocarcinoma in patients with primary sclerosing cholangitis is encouraged,
but there is no general consensus on the modality and interval of choice.
Colon cancer is also associated with PSC.
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 and approximately 70% of people with primary sclerosing cholangitis have ulcerative
colitis.
Epidemiology There is a 2:1 male-to-female predilection
of primary sclerosing cholangitis.
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.
See also Progressive familial intrahepatic cholestasis
Chris Klug - professional snowboarder with PSC who had liver transplant
Chris LeDoux - professional rodeo rider and country musician with PSC who died of cholangiocarcinoma
Elena Baltacha - professional British tennis player, diagnosed with PSC at age 19 and died
five months after being diagnosed with liver cancer, age 30.
Walter Payton - died of primary sclerosing cholangitis
References
External links PSC Partners: Patient organization with additional
information PSC Support: Charity with additional information,
discussion forum and support tools for those affected by PSC
Additional Literature about PSC Information from The Morgan Foundation for
the Study of PSC