Finding the Patient With Primary Biliary Cirrhosis

Rowen K. Zetterman, MD


February 27, 2015

In This Article

Laboratory Findings

The hallmark of PBC is the presence of AMAs directed against the E2 subcomponent of the pyruvate dehydrogenase complex (PDC-E2) located on the intermitochondrial membrane.[27] AMAs are present in 90%-95% of patients with PBC, with women more likely than men to be AMA positive (95% vs 25%, respectively). AMA-negative PBC occurs and is clinically similar to AMA-positive disease.[28]

Antinuclear antibodies (ANA) occur in 30% of patients with PBC. Two disease-specific ANAs targeting the nuclear body and nuclear membrane have been identified in PBC.[12] Antibody to nuclear pore membrane protein gp210 and to nuclear body protein sp100 may assist in the diagnosis of PBC, especially when the AMA titer is negative. These ANAs appear to be markers of more aggressive disease and poor prognosis when present.[29]

Alkaline phosphatase levels tend to be increased fivefold to 10-fold, with mild to moderate elevation of aminotransferase levels. Serum bilirubin levels are often normal at the initial diagnosis of PBC, and the progressive increase in bilirubin can be a sign of worsening fibrosis[30] and poor prognosis. Although it is uncommon, up to 10% of patients with PBC will initially present with jaundice from the rapid development of ductopenia.[31]

Typical laboratory findings of PBC include the following:

Positive AMA titer;

Elevated alkaline phosphatase level;


Elevated IgM level;

Hypercholesterolemia; and

Marked elevation of the erythrocyte sedimentation rate.

Radiologic Findings

There are no diagnostic findings of PBC on hepatic ultrasonography, CT, or MRI. Hepatomegaly, hilar adenopathy, splenomegaly, and signs of portal hypertension in the presence of advanced liver disease from fibrosis or cirrhosis may be noted. Pulmonary fibrosis may be seen with pulmonary radiographic studies.


The histologic hallmark of PBC is biliary epithelial cell destruction leading to the eventual loss of small interlobular bile ducts. Chronic necroinflammatory liver disease with portal tract mononuclear inflammation, nonsuppurative cholangitis, portal tract bile duct loss, and pericentral cholestasis can be present.[26] In early disease, eosinophilia and granulomata of portal areas may occur. Portal mononuclear inflammation includes CD4 positive, CD8 positive, and natural killer T cells.

The florid duct lesions characteristic of PBC can be focal and spotty, and progressive ductopenia occurs with disease progression. Copper stains may show periportal copper accumulation associated with cholestasis.

Progression of histologic disease to significant fibrosis and cirrhosis is characteristic. The histologic features of PBC can be classified into four broad stages (Table).

Table. Histologic Stages of Primary Biliary Cirrhosis

Stage Features
1 Focal bile duct destruction, mononuclear portal inflammation, with or without portal tract eosinophils, and granulomata
2 Bile duct destruction, interlobular duct loss, proliferation of bile ducts, portal tract and interface inflammation, and portal fibrosis
3 Periportal fibrosis with bridging fibrosis between portal areas, bile duct loss, and cholestasis
4 Cirrhosis, ductopenia, and cholestasis


Making the Diagnosis of PBC

The diagnosis of PBC is usually established in a patient with itching or fatigue, in association with liver tests indicative of cholestasis, a positive AMA titer, and typical findings on liver histology.

In patients with AMA-negative disease, the presence of typical histology, hypercholesterolemia, hypergammaglobulinemia, increased IgM level, and elevation of sedimentation rate can assist with the diagnosis.[32] The clinical course of AMA-negative PBC is similar to that of AMA-positive disease.


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