Cholangitis, Primary Biliary

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 lipoprotein X), 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 ...