- Author: Robert P Myers, MD, FRCPC; Chief Editor: BS Anand, MD more...
Liver enzymes (alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, and gamma-glutamyl transpeptidase) should be assessed. Patients typically have a cholestatic liver profile with predominant elevations of alkaline phosphatase and gamma-glutamyl transpeptidase. Aminotransferase levels may be within the reference range or be moderately elevated.
Serum bilirubin levels may range from within the reference range to displaying marked elevation. The bilirubin level may rise insidiously in association with gradual progression of the disease or rise abruptly with intermittent episodes of fever and abdominal pain suggesting acute cholangitis.
In the early stages of the disease, the prothrombin time (PT) and the albumin level typically are within the reference ranges, although the albumin level may be decreased as a consequence of coexisting inflammatory bowel disease (IBD). As the disease progresses to later stages, the PT may rise and the albumin may fall.
Patients may have coexistent risk factors for the acquisition of viral hepatitis, including the blood transfusions that are often necessary for the management of anemia in patients with IBD. Rule out chronic hepatitis B and C with hepatitis B surface antigen (HBsAg) and antihepatitis C (anti-HCV) antibody tests. Hypergammaglobulinemia and hypercholesterolemia have been reported in some patients.
The perinuclear antineutrophil cytoplasmic antibody (pANCA) test reveals a reported prevalence of 26-85% in classic primary sclerosing cholangitis (PSC). In one study, the sensitivity and specificity of pANCA testing with the immunofluorescence technique were 51% and 73%, respectively. The usefulness of the pANCA test in pericholangitis is not clear.
Antimitochondrial antibody testing should be ordered to rule out primary biliary cirrhosis (PBC), a common cause of cholestatic liver disease. Patients with pericholangitis characteristically lack this antibody.
Antinuclear antibodies (ANA), smooth muscle antibodies (SMA), or both have been reported in 28% of patients with pericholangitis. Tests for these antibodies should be ordered to rule out autoimmune hepatitis as a cause of liver biochemical abnormalities, although this condition typically presents with elevated levels of aminotransferases rather than a cholestatic liver profile.
Autoantigen testing may prove useful in this setting. A study by Ardesjo et al reported the identification of a novel staining pattern of bile duct epithelial cells in patients with PSC, which appeared to have potential utility as an early diagnostic marker.
The investigators used immunostaining on normal human bile duct with sera from affected patients and control patients, then constructed a cDNA library from normal human bile duct and immunoscreened patient sera to identify an autoantigen. Finally, using in vitro transcription and translation and immunoprecipitation, they assessed immunoreactivity against PDZ domain containing 1 (PDZK1) in patients with PSC (n = 35), control patients (n = 198), and healthy control subjects (n = 94).
The PSC sera stained cytoplasmic granules and apical cell membranes of biliary epithelial cells in a novel staining pattern. Strong immunoreactivity to these structures were found in 12 of 35 (34%) PSC sera but not in sera from the healthy control subjects. When the cDNA library was screened, PDZK1 was identified as a potential new autoantigen. Strong immunoreactivity to PDZK1 was detected in 1% of healthy controls, 2% of IBD patients, 8% of autoimmune pancreatitis patients, 9% of PSC patients, and 18% of Graves disease patients.
One study suggests that U2 small nuclear RNA fragments in the bile fluid may be a potential diagnostic marker for cholangiocarcinoma. Baraniskin et al reported that significantly higher bile levels of U2 RNA fragments in those with cholangiocarcinoma allowed differentiation from PSC, as measured by real-time PCR normalized to cel-54 (67% sensitivity, 91% specificity).
No specific ultrasonographic findings exist for the diagnosis of pericholangitis. Perform abdominal ultrasonography to screen for other causes of hepatic pathology, including fatty liver and cholelithiasis, which also may affect patients with IBD. Although ultrasonography is insensitive, it may detect findings suggestive of cirrhosis such as a nodular, shrunken liver, or portal hypertensive changes, including splenomegaly, altered portal venous blood flow, or the formation of venous collaterals.
Perform endoscopic retrograde cholangiopancreatography (ERCP) to rule out large-duct PSC, a much more common cause of cholestasis in patients with IBD. Findings include stricturing and beading of the intrahepatic or extrahepatic bile ducts. By definition, ERCP findings are normal in patients with pericholangitis. However, some patients with large-duct PSC may have histologic evidence of pericholangitis or small-duct disease.
The role of magnetic resonance cholangiopancreatography (MRCP) in pericholangitis is unclear. Preliminary studies suggest that MRCP may be as useful as ERCP in detecting the typical cholangiographic features of PSC. MRCP findings are normal in patients with pericholangitis.
Performing a liver biopsy is essential for the diagnosis and staging of pericholangitis and to rule out other causes of liver disease.
Bleeding is the predominant risk associated with liver biopsy. Fatal and nonfatal hemorrhages have been reported in 0.04% and 0.16% of patients, respectively. Ultrasound guidance may reduce the risk of complications.
Pericholangitis may be classified into 4 stages on the basis of histologic findings. The histologic stage is an important predictor of survival in PSC and likely bears the same importance in pericholangitis.
Stage 1 (portal stage) is characterized as follows:
Lymphocytic portal inflammation, accompanied with variable amounts of edema, fibrosis, and bile ductular proliferation
Most ducts are without an abnormality, but some show degenerative changes, periductal fibrosis, and nonsuppurative fibrous cholangitis (the typical “onion-skin lesion” of PSC)
Stage 2 (periportal stage) is characterized as follows:
Periportal fibrosis with or without periportal hepatitis, and expansion of the portal triads with seemingly intact newly formed limiting plates
Focal ductopenia often is noted in this stage
Stage 3 (septal stage) is characterized as follows:
Septal fibrosis, bridging necrosis, or both are prominent
Bile ducts often are severely damaged or absent
Other features include piecemeal necrosis and prominent copper deposition
Stage 4 (cirrhotic stage) is characterized as follows:
The liver is cirrhotic, and bile ducts often have disappeared
At this stage, differentiation from other cholestatic liver diseases, particularly primary biliary cirrhosis (PBC), may be difficult
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