Primary Biliary Cholangitis

Primary biliary cholangitis (PBC) is a chronic disease resulting in autoimmune destruction of the intrahepatic bile ducts. The typical presentation is that of a middle-aged woman with pruritus, fatigue, and right upper quadrant abdominal pain. Elevated liver enzymes and antimitochondrial antibodies (AMAs) establish the diagnosis. Medical management is limited to using ursodeoxycholic acid, a disease-modifying agent. Definitive treatment is liver transplantation, which is performed in late stages (cirrhosis).

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Overview

Epidemiology

  • More prevalent in women than men
  • Highest prevalence in Europe and North America
  • Most commonly diagnosed in 4th to 6th decades of life
  • Primary biliary cholangitis (PBC) accounts for < 1% of liver transplantations in the United States.

Etiology

  • There is a presumed autoimmune etiology.
  • Associated with:
    • Sjögren’s syndrome
    • Scleroderma
    • CREST (calcinosis, Raynaud’s phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome
    • Rheumatoid arthritis
    • Hashimoto’s thyroiditis
  • Possible genetic risk
  • Patients have ↑ incidence of gram-negative urinary tract infections.

Pathophysiology

  • The exact mechanism is not known.
  • Chronic, progressive liver disease → cholestasis and autoimmune destruction of intrahepatic bile ducts → gradual portal and periportal fibrosis → liver cirrhosis and portal hypertension → liver failure

Clinical Presentation

Primary biliary cholangitis has a wide range of symptoms. The condition is often asymptomatic in the early phase and features symptoms of decompensated cirrhosis in the late phase.

  • Acute presentation: 
    • Pruritus
    • Fatigue 
  • Chronic presentation: 
    • Hepatomegaly +/- splenomegaly
    • Jaundice
    • Melanosis (darkening skin)
    • Xanthomas (fatty cholesterol deposits underneath the skin) and xanthelasma (xanthomas around the eyelids) 
  • End-stage: 
    • Hepatocellular failure (cirrhosis)
    • Portal hypertension (ascites, variceal bleeding, etc.)
  • High incidence of osteoporosis due to vitamin D deficiency

Jaundice: yellow discoloration of the skin due to bilirubin deposition

Image: “Jaundice08” by James Heilman, MD. License: CC BY 3.0

Diagnosis and Management

Diagnosis

  • Blood tests:
    • ↑ Antimitochondrial antibodies (AMA) is diagnostic (> 95% specificity and sensitivity)
    • Transaminases: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are slightly
    • ↑ Alkaline phosphatase (ALP) 
    • ↑ Conjugated bilirubin
    • ↑ Gamma-glutamyl transferase
  • Liver biopsy:
    • Not required → can confirm the diagnosis
    • More useful for staging (prognostic indicator)

Management

  • Liver transplantation is the only definitive treatment.
  • 1st-line agent: ursodeoxycholic acid (UDCA, ursodiol)
    • Up to 40% of patients do not respond.
    • Alternative: obeticholic acid (OCA)
  • Cholestyramine may be used for pruritus and hypercholesterolemia.
  • Calcium and vitamin D supplementation for low bone density
  • Bisphosphonates given for severe osteoporosis

Primary biliary cirrhosis, demonstrating chronic nonsuppurative destructive cholangitis: Infiltration of lymphocyte (arrow) and plasma cell (bold arrow) into the bile duct is shown.

Image: “Primary biliary cirrhosis” by Department of Medicine, Toronto Western Hospital (University Health Network/University of Toronto), Toronto, Ontario, Canada. License: CC BY 2.0

Differential Diagnosis

  • Primary sclerosing cholangitis: an inflammatory disease of the bile ducts that causes narrowing of the biliary tree due to scarring. Associated with ulcerative colitis. Patients present with fatigue, pruritus, and icterus. Diagnosis is by MRCP (magnetic resonance cholangiopancreatography) and management is symptomatic. Definitive treatment is liver transplantation in late stages (cirrhosis).
  • Bile duct obstruction: an obstruction of the biliary system that also presents with jaundice and increased cholestasis laboratories. The acute onset of jaundice, right upper quadrant pain, and a higher elevation of aminotransferases help differentiate the condition from PBC. Further differentiation can be made by ultrasound or MRCP. Biliary obstructions have many causes, including gallstones and tumors. Treatment is based on etiology. 
  • Autoimmune hepatitis: liver inflammation that occurs when the body’s immune system turns against liver cells. Clinical presentation ranges from asymptomatic to symptoms of acute liver failure. Diagnosed by testing for serum anti-smooth muscle antibodies and liver biopsy. Treatment is with corticosteroids and azathioprine. With early treatment, the prognosis is favorable. If left untreated, half of patients die in the first few years.

References

  1. Poupin, R. (2020). Clinical manifestations, diagnosis, and prognosis of primary biliary cholangitis (primary biliary cirrhosis). UpToDate. Retrieved November 10, 2020 from https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-prognosis-of-primary-biliary-cholangitis-primary-biliary-cirrhosis?search=primary%20biliary%20cirrhosis&source=search_result&selectedTitle=1~144&usage_type=default&display_rank=1#H58140968
  2. Gonzalez, R. S., & Washington, K. (2018). Primary Biliary Cholangitis and Autoimmune Hepatitis. Surgical pathology clinics, 11(2), 329–349. https://doi.org/10.1016/j.path.2018.02.010
  3. Floreani, A., & Mangini, C. (2018). Primary biliary cholangitis: Old and novel therapy. European journal of internal medicine, 47, 1–5. https://doi.org/10.1016/j.ejim.2017.06.020
  4. Gulamhusein, A. F., & Hirschfield, G. M. (2018). Pathophysiology of primary biliary cholangitis. Best practice & research. Clinical gastroenterology, 34-35, 17–25. https://doi.org/10.1016/j.bpg.2018.05.012
  5. Yang, M. Y., Kim, J. M., Kim, G. W., Kim, H. S., Kim, B. S., Kim, M. B., & Ko, H. C. (2017). Xanthoma Striatum Palmare in a Patient of Primary Biliary Cirrhosis with Autoimmune Hepatitis. Annals of dermatology, 29(3), 358–359. https://doi.org/10.5021/ad.2017.29.3.358

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