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For further information, see CMDT Part 16-12: Primary Biliary Cholangitis

Key Features

Essentials of Diagnosis

  • Occurs in middle-aged women

  • Often asymptomatic

  • Elevated serum alkaline phosphatase, IgM, and cholesterol; positive antimitochondrial antibodies (AMA)

  • Characteristic liver biopsy

  • In later stages, can present with fatigue, jaundice, features of cirrhosis, xanthelasma, xanthomata, steatorrhea

General Considerations

  • Chronic disease of the liver characterized by autoimmune destruction of small intrahepatic bile ducts and cholestasis

  • The designation "primary biliary cholangitis" has been proposed instead of primary biliary cirrhosis because many patients do not have cirrhosis

  • Insidious in onset

  • Occurs usually in women aged 40–60

  • Often detected by the chance finding of elevated serum alkaline phosphatase levels

  • It may be associated with

    • Sjögren syndrome

    • Autoimmune thyroid disease

    • Raynaud syndrome

    • Scleroderma

    • Hypothyroidism

    • Gluten enteropathy

  • Infection with Novospingobium aromaticivorans and Chlamydophila pneumoniae may trigger or cause primary biliary cholangitis; other triggers include viruses, lactobacillus vaccination, and xenobiotics

  • Risk factors include

    • History of urinary tract infections

    • Smoking

    • Hormone replacement therapy

    • Use of hair dye

  • Patients with a clinical and histologic picture of primary biliary cholangitis but with no AMA are said to have AMA-negative primary biliary cholangitis ("autoimmune cholangitis"), which has been associated with

    • Lower serum IgM levels

    • Greater frequency of smooth muscle antibodies and antinuclear antibodies

Demographics

  • Estimated incidence and prevalence rates in the United States

    • In women: 4.5 and 65.4 per 100,000, respectively

    • In men: 0.7 and 12.1 per 100,000, respectively

Clinical Findings

Symptoms and Signs

  • Many are asymptomatic for years

  • The onset of clinical illness is insidious and is heralded by fatigue and pruritus

  • With progression, physical examination reveals hepatosplenomegaly

  • Xanthomatous lesions may occur in the skin and tendons and around the eyelids

  • Jaundice, steatorrhea, and signs of portal hypertension are late findings, although occasional patients have esophageal varices despite an early histologic stage

  • Autonomic dysfunction, including orthostatic hypotension, associated with fatigue, and cognitive dysfunction appear to be common

  • The risk of low bone density, osteoporosis, and fractures is increased, as in patients with other forms of chronic liver disease

Differential Diagnosis

  • Chronic biliary tract obstruction (stone or stricture)

  • Carcinoma of the bile ducts

  • Primary sclerosing cholangitis

  • Sarcoidosis

  • Cholestatic drug toxicity (eg, chlorpromazine)

  • Chronic hepatitis

  • Some patients have overlapping features of primary biliary cholangitis and autoimmune hepatitis

Diagnosis

Laboratory Tests

  • Blood cell counts are normal early in the disease

  • Liver biochemical tests reflect cholestasis with elevation of serum alkaline phosphatase, cholesterol (especially high-density lipoproteins), and, in later stages, bilirubin

  • Antimitochondrial antibodies (AMA)

    • Directed against pyruvate dehydrogenase or other 2-oxo-acid enzymes in mitochondria

    • Present in 95% of patients

    • Titer > 1:40 in serum

  • Serum IgM levels are elevated

  • Antinuclear antibodies directed against the nuclear pore complex may be detected in specialized laboratories

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