Primary Sclerosing Cholangitis

 May affect large bile ducts (both intra- and extrahepatic), small bile ducts, or both






Etiology/Pathogenesis




• Unknown etiology
image Frequent association with inflammatory bowel disease, particularly ulcerative colitis


Clinical Issues




• Predilection for young and middle-aged men
• Majority of patients are asymptomatic at diagnosis

• Elevated alkaline phosphatase in over 90% of patients

• Progresses to biliary cirrhosis in majority of patients within 10-15 years

• Essentially no effective medical therapy

image Liver transplantation for end-stage liver disease

• Increased risk of cholangiocarcinoma, colorectal carcinoma, and gallbladder carcinoma


Imaging




• Cholangiography is diagnostic gold standard
image Characteristic beaded appearance of biliary tree secondary to segmental strictures


Microscopic




• Findings often patchy and nonspecific, making biopsy diagnosis difficult
image Concentric fibrosis around affected bile ducts with onion skin appearance

– Present only in minority of biopsy samples

• Lymphocytic cholangitis

• Degeneration and atrophy of duct epithelium
image Eventual obliteration of ducts with variable scarring

• Periportal copper deposition indicates chronic cholestasis

image
ERCP
A classic ERCP of primary sclerosing cholangitis (PSC) shows multiple segmental strictures of the biliary tree, resulting in a beaded appearance image. There are also diverticular outpouchings of dilated bile ducts image .


image
Onion Skin Lesion
The classic onion skin lesion of PSC consists of concentric fibrosis around a bile duct. There is mild lymphoplasmacytic infiltration of the portal tract and lymphocytic cholangitis in the duct epithelium.

image
Inflammation and Duct Damage
This case of PSC shows markedly damaged duct epithelium, as well as lymphoplasmacytic infiltration of the duct, periductal stroma, and portal tract. Lymphocytic cholangitis is apparent within the remaining ductal epithelium image .

image
Duct Loss With Scar
This interlobular bile duct has been entirely replaced by a round fibroobliterative scar image. The hepatic artery and portal vein branches are unremarkable.


TERMINOLOGY


Abbreviations




• Primary sclerosing cholangitis (PSC)


Definitions




• Chronic cholestatic disease featuring progressive inflammation and fibrosis of intrahepatic and extrahepatic biliary tree


ETIOLOGY/PATHOGENESIS


Unknown




• Frequent association with HLA-B8 and DR3
image 100x increased risk of disease in 1st-degree relatives of patients with PSC

• Associated with chronic idiopathic inflammatory bowel disease (IBD), particularly ulcerative colitis
image ∼ 70% of patients with PSC have ulcerative colitis

image 2.0-7.5% of patients with ulcerative colitis have PSC

image 1.4-3.4% of patients with Crohn disease have PSC

• May affect large bile ducts (both intra- and extrahepatic), small bile ducts, or both


CLINICAL ISSUES


Epidemiology




• Incidence
image ∼ 1 in 100,000 people

– Highest in people with Northern European ancestry

• Age
image Any age, common from 20-50 years
– Median: 35-47

• Sex
image Close to 70% of patients are male


Presentation




• Majority of patients are asymptomatic at diagnosis
image Diagnosis often results from investigation of abnormal liver tests

• Nonspecific signs/symptoms
image Fatigue

image Abdominal pain

image Pruritus/jaundice

image Weight loss


Laboratory Tests




• Elevated alkaline phosphatase in > 90% of patients
• Transaminases may be 2-3x normal limits but may not be elevated

• Bilirubin typically normal at diagnosis

image Elevation more common in advanced disease

• Nonspecific antibodies often present including ANA, SMA, ANCA


Treatment




• Essentially no effective medical therapy
image Use of ursodeoxycholic acid controversial

• Endoscopic balloon dilation or stenting

• Liver transplantation for end-stage liver disease
image Reportedly recurs in up to 1/2 of transplant recipients within 10 years


Prognosis




• Progresses to biliary cirrhosis in majority of patients within 10-15 years
image Slightly < 20% of asymptomatic patients have cirrhosis at time of diagnosis

• Increased risk of cholangiocarcinoma
image 160x higher than general population

image Risk factors include older age at PSC diagnosis, smoking, alcohol use, longer duration of IBD

image Surveillance is recommended (imaging and serum CA19-9 level)
– Effectiveness of surveillance is unclear

• Increased risk of gallbladder carcinoma
image 2% of patients with PSC

• Increased risk of colorectal adenocarcinoma
image Higher than in patients with IBD alone
– Patients who have undergone liver transplant for PSC may have even greater risk than pretransplant

image Frequent (every 1-2 year) colonoscopy is recommended

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Apr 20, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Primary Sclerosing Cholangitis

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