primary%20biliary%20cholangitis
PRIMARY BILIARY CHOLANGITIS

Primary biliary cholangitis (formerly primary biliary cirrhosis) is a chronic, progressive, autoimmune, cholestatic liver disease more common in middle-aged women. It is characterized by destruction of small to medium bile ducts leading to cholestasis and frequently, end-stage liver disease.
Diagnostic features are chronic biochemical cholestasis, presence of antimitochondrial antibodies and the characteristic liver biopsy findings.


 

Pharmacotherapy

  • All PBC patients with abnormal liver biochemistry are possible candidates for specific therapy  
  • Treatment goals are to prevent end-stage liver disease and to manage PBC-associated symptoms affecting patient’s quality of life 

Ursodeoxycholic Acid (UDCA)

  • Patients with abnormal liver biochemistry (regardless of histologic stage) and confirmed PBC should be given UDCA
  • Chief medication used to deter disease progression
  • Action: Increases the rate of transport of intracellular bile acids across the liver cell and into the canaliculus, thus reducing hydrophobic bile acid levels inside hepatic cells
    • May have anti-inflammatory, choleretic, cytoprotective and immunomodulatory effects
  • Results in significant improvement in biochemical markers of cholestasis (ALP, GGT, bilirubin, AST, ALT); decreased serum LDL cholesterol; decreased AMA titers
  • UDCA therapy results in a significant increase in survival after up to 4 years of treatment, thus delaying the need for liver transplantation
    • The biggest benefit is seen in those with the most severe disease
  • UDCA also protects PBC patients from developing hepatoma
  • UDCA use may have little effect on symptoms
    • The drug may delay development of portal hypertension
    • Treatment reduces the rate of development of esophageal varices, but does not reduce the rate of bleeding from these varices
    • There has been no evidence that UDCA decreases fatigue or pruritus, or that it has any benefit on osteoporosis or autoimmune features associated with PBC
  • Patient compliance may be better when a single daily dose is used, compared to divided doses
    • Single daily dose is just as effective as divided doses
  • Assess biochemical response after 1 year of UDCA therapy 

Obeticholic Acid (OCA)

  • May be used as monotherapy in patients intolerant to UDCA or in combination with UDCA in patients with inadequate response to a year of UDCA therapy 
  • Action: Modulates the synthesis, absorption, transport, secretion and metabolism of bile acids resulting to a choleretic effect 
  • Liver chemistries and inflammatory markers improved with therapy 
  • Most common adverse effect is pruritus 
  • Use is not recommended in decompensated PBC

Other Agents

  • Fibrates may be considered as an off-label therapy in patients with inadequate response to UDCA therapy but not in those with decompensated liver disease
  • Immunosuppressive drugs have been studied for PBC because of the autoimmune nature of the disease
    • Immunosuppressive therapy, in addition to UDCA, may benefit PBC patients with AIH   
    • Corticosteroids combined with UDCA had shown improvement of liver function serum parameters and histologic grades in controlled trials
      • Budesonide in combination with UDCA had been shown in clinical trials to improve liver function serum parameters as well as liver histology in patients with grade I-III fibrosis
    • A few studies have shown some benefits from treatment with Azathioprine and Ciclosporin but adverse effects may limit usefulness
    • Studies have found insufficient evidence regarding the benefit of additional treatment with Colchicine, Methotrexate, or Silymarin
  • Mycophenolate mofetil, Chlorambucil, Penicillamine, Thalidomide, Seladelpar, leukotriene antagonists, antiretrovirals, molecular therapies, and monoclonal antibodies are promising therapies that are currently being studied
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