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Primary Biliary Cholangitis (Primary Biliary Cirrhosis)

Practice Essentials

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is a chronic disease of the liver, presumably autoimmune in nature, that leads to progressive cholestasis and often end-stage liver disease (see the image below). The name change reflects the fact that cirrhosis occurs only in the late stage and therefore does not correctly identify patients with early-stage disease.

PBC is most frequently a disease of women and occurs between the fourth and sixth decades of life.

This histologic picture is compatible with stage 2

This histologic picture is compatible with stage 2 primary biliary cholangitis.

Signs and symptoms

Of patients with PBC, 25% are incidentally diagnosed during a routine blood evaluation. Symptoms of PBC include the following:

Fatigue (65% of patients): The first reported symptom

Pruritus (55%)

Right upper quadrant discomfort (8-17%)

Physical examination findings depend on the stage of the disease. In the early stages, examination findings are normal. As the disease advances, the following signs may be noted:

Hepatomegaly (25%)

Hyperpigmentation (25%)

Splenomegaly (15%)

Jaundice (10%)

Xanthomas and Xanthelasmas (10%): In late stages of the disease

Sicca syndrome (50-75%): Xerophthalmia (ie, dry eyes), xerostomia (ie, dry mouth)

Kayser-Fleischer rings (extremely rare)

In patients with advanced disease, the findings may include the following stigmata of cirrhosis:

Spider nevi

Palmar erythema

Ascites

Temporal and proximal muscle wasting

Peripheral edema

See Clinical Presentation for more detail.

Diagnosis

Abnormalities on laboratory studies include the following:

Significant elevations of the alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGTP), and immunoglobulin levels (mainly IgM): Usually the most prominent findings

Elevation of the aminotransferases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels

Increased lipid and cholesterol levels, with an increased HDL fraction

Increased erythrocyte sedimentation rate

Elevated bilirubin level, prolonged prothrombin time, and decreased albumin level: Indicate progression of disease to cirrhosis

Thrombocytopenia: Indicates portal hypertension

Antinuclear antibodies (ANAs): Can be identified in 20-50% of patients with PBC

Less common abnormalities include elevated levels of the following:

Ceruloplasmin

Bile acids

Serum hyaluronate

The hallmark of PBC is the presence of antimitochondrial antibodies (AMAs) in serum. AMAs can be found in 90-95% of patients with PBC, and they have a specificity of 98% for this disease. Four AMA profiles occur:

Profile A: Positive for anti-M9 only

Profile B: Anti-M9 and/or anti-M2–positive by ELISA

Profile C: Anti-M2, anti-M4, and/or anti-M8–positive by ELISA

Profile D: Anti-M2, anti-M4, and/or anti-M8–positive by ELISA and complement-fixation test

Patients with profile A or B have a better disease course than patients with profile C or D.

Some patients have clinical, biochemical, and histologic features of PBC, but their sera are negative for AMA. The diagnosis of autoimmune cholangitis has been used for these patients.

Imaging studies

Abdominal ultrasonography, CT scanning, or 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 cirrhosis develops, findings compatible with portal hypertension can be observed, including the following:

Nodular appearance of the liver

Splenomegaly

Intra-abdominal varices

Ascites

In patients with cirrhosis, follow-up imaging every 6 months with abdominal ultrasonography is suggested for early detection of hepatic malignancy.

Staging

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

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

See Workup for more detail.

Management

Pharmacologic treatment of PBC is as follows:

Ursodeoxycholic acid (UDCA) is the major medication used to slow the progression of the disease

Obeticholic acid may be considered in combination with UDCA in adults with an inadequate response to UDCA for at least 1 year or as monotherapy in adults unable to tolerate UDCA

Methotrexate may produce improvement in biochemical and histologic findings

Corticosteroids may alleviate symptoms and improve biochemical and histologic findings

Cyclosporine has some therapeutic potential

Colchicine has been used with limited effect

Pruritus is often refractory to medical therapy and significantly impacts the patient’s quality of life. Antipruritic treatment is as follows:

Antihistamines are the first-line agents for patients with mild-to-moderate pruritus, but can further depress brain function in patients with cirrhosis and signs of encephalopathy

Cholestyramine and colestipol sequester bile salts in the enteric lumen; a 1- to 4-day delay is expected before the itching remits

Rifampin can also be used for pruritus unresponsive to cholestyramine

Dronabinol (Marinol) use is supported by some evidence

Plasmapheresis may be effective in patients with severe pruritus intractable to medical treatment

In patients with cirrhosis, an elevated bilirubin level is an ominous sign of disease progression, and liver transplantation must be considered. Liver transplantation appears to be the only life-saving therapeutic option.

See Treatment and Medication for more detail.

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