Primary Biliary Cholangitis (Primary Biliary Cirrhosis) Workup

Updated: Nov 08, 2017
  • Author: Nikolaos T Pyrsopoulos, MD, PhD, MBA, FACP, AGAF, FAASLD, FRCP(Edin); Chief Editor: BS Anand, MD  more...
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Laboratory Studies

Consider the following:

  • An elevation of the aminotransferases: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) may be identified in most patients with primary biliary cholangitis, but significant elevations of the alkaline phosphatase (ALP), γ -glutamyl transpeptidase (GGTP), and immunoglobulin levels (mainly immunoglobulin M [IgM]) are usually the most prominent findings.

  • Lipid levels and cholesterol levels may be increased, with an increased high-density lipoprotein (HDL) fraction. The latter finding explains why these patients do not have an increased risk for atherosclerosis.

  • An increased erythrocyte sedimentation rate is another finding.

  • As the disease progresses to cirrhosis, an elevated bilirubin level, a prolonged prothrombin time, and a decreased albumin level can be found. The increased bilirubin level is an ominous sign of disease progression, and liver transplantation must be considered.

  • Thrombocytopenia is indicative of portal hypertension. Additionally, but not as commonly, abnormalities include elevated levels of ceruloplasmin, bile acids, and serum hyaluronate.

The hallmark of this disease is the presence of antimitochondrial antibodies (AMAs) in the sera. Note the following:

  • AMAs can be found in 90-95% of patients with primary biliary cholangitis, and they have a specificity of 98% for this disease.

  • These antibodies target different components, mainly enzymes, in the mitochondria.

  • The presence of anti-M2, anti-M4, anti-M8, and anti-M9 has been associated with the severity of primary biliary cholangitis. Patients with profile A (ie, only anti-M9) or profile B (ie, anti-M9 and/or anti-M2–positive by enzyme-linked immunosorbent assay [ELISA]) have a better disease course than patients with profile C (ie, anti-M2, anti-M4, and/or anti-M8–positive by ELISA) and profile D (ie, anti-M2, anti-M4, and/or anti-M8–positive by ELISA and complement-fixation test).

  • Antinuclear antibodies (ANAs) can be identified in 20-50% of patients with primary biliary cholangitis

  • Some patients have clinical, biochemical, and histologic features of primary biliary cholangitis, but their sera are negative for AMA. The diagnosis of autoimmune cholangitis has been used for these patients, but whether these patients represent the AMA-negative primary biliary cholangitis group is a matter of debate. In terms of autoimmune markers, their profile is compatible with this type of autoimmune hepatitis (ie, high-titer ANA and/or SMA).

  • The natural history and associated autoimmune conditions in AMA-positive and AMA-negative primary biliary cholangitis appear to be identical. A careful review of the liver biochemical pattern reveals cholestasis (ie, ALP and GGTP are elevated), and the liver biopsy findings are compatible with bile duct injury, ductopenia, cholestasis, and granulomas. [8]


Imaging Studies

Abdominal ultrasonography, computed tomography (CT) scanning, or magnetic resonance imaging (MRI) are important to exclude biliary obstruction.

Nonspecific findings include increased echogenicity of the liver parenchyma and findings compatible with portal hypertension.

Portal lymphadenopathy can be recognized in approximately 15% of these patients.

Once patients are cirrhotic, findings compatible with portal hypertension (eg, nodular appearance of the liver, splenomegaly, intra-abdominal varices, ascites) can be observed. At this stage, follow-up imaging every 6 months with abdominal ultrasonography is suggested for early detection of hepatic malignancy.



The diagnosis of primary biliary cholangitis should be established or confirmed by performing a percutaneous or laparoscopic liver biopsy. This procedure also provides additional information about the stage of the disease and the patient's prognosis.

In the late stages of the disease (ie, cirrhosis), an upper endoscopy study should be performed. If the patient has developed esophageal varices, prophylactic treatment (eg, beta-blockers, nitrates) can be initiated in an attempt to prevent variceal bleeding.


Histologic Findings

Primary biliary cholangitis is characterized by chronic, nonsuppurative, destructive cholangitis of the small interlobular bile ducts with a diameter of 40-80 mm. Early lesions signal damage of the basement membrane of the bile ducts and reactive hyperplasia of the epithelial lining. Lymphocytic and plasma cell infiltration, with eosinophilic condensation in the portal tracts, is another feature. Epithelioid aggregates or granulomas may be found around the bile ducts. Fibrosis and cirrhosis develop later.



Various staging systems have been developed, but the most prominent are those proposed by Ludwig et al and Scheuer, as follows [9] :

  • Stage 1 (portal stage of Ludwig): Portal inflammation, bile duct abnormalities, or both are present.

  • Stage 2 (periportal stage): Periportal fibrosis is present, with or without periportal inflammation or prominent enlargement of the portal tracts with seemingly intact, newly formed limiting plates. See the image below.

    This histologic picture is compatible with stage 2 This histologic picture is compatible with stage 2 primary biliary cholangitis.
  • Stage 3 (septal stage): Septal fibrosis with active inflammatory, passive paucicellular septa, or both are present.

  • Stage 4 (cirrhosis): Nodules with various degrees of inflammation are present.