primary%20biliary%20cirrhosis
PRIMARY BILIARY CIRRHOSIS

Primary biliary cirrhosis is 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.
At present, the diagnosis is most often made in an asymptomatic patient who presents with abnormal lab results on a routine checkup or as part of workup for an associated illness.


 

Principles of Therapy

  • All primary biliary cirrhosis (PBC) patients w/ abnormal liver biochemistry are possible candidates for specific therapy

Pharmacotherapy

Ursodeoxycholic Acid (UDCA)

  • Patients w/ abnormal liver biochemistry & confirmed primary biliary cirrhosis (PBC) should be given ursodeoxycholic acid (UDCA)
  • Ursodeoxycholic acid (UDCA) is the chief medication used to deter disease progression
  • Action: Increases the rate of transport of intracellular bile acids across the liver cell & into the canaliculus, thus reducing hydrophobic bile acid levels inside hepatic cells
    • May have cytoprotective effects & immunomodulatory effect
  • Significant improvement in biochemical markers of cholestasis [alkaline phosphatase (ALP), gamma-glutamyl transpeptidase, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT)]; decreased serum cholesterol; decreased antimitochondrial antibody (AMA) titers
  • Ursodeoxycholic acid (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 w/ the most severe disease
  • Ursodeoxycholic acid (UDCA) also protects primary biliary cirrhosis (PBC) patients from developing hepatoma
  • Ursodeoxycholic acid (UDCA) use may have little effect on symptoms
    • The drug may result in some improvement of pruritus & 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 ursodeoxycholic acid (UDCA) decreases fatigue or that it has any benefit on osteoporosis
  • 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

Other Agents

Immunosuppressants

  • Immunosuppressive drugs have been studied for primary biliary cirrhosis (PBC) because of the presumed autoimmune nature of the disease
  • Corticosteroids combined w/ ursodeoxycholic acid (UDCA) had shown improvement of liver function serum parameters & histologic grades in controlled trials
    • Budesonide in combination w/ ursodeoxycholic acid (UDCA) had been shown in clinical trials to improve liver function serum parameters as well as liver histology in patients w/ grade I-III fibrosis
  • A few studies have shown some benefits from treatment w/ Azathioprine & Ciclosporin but adverse effects may limit usefulness
  • Recent reviews have found insufficient evidence regarding the benefit of treatment w/ Colchicine, or Methotrexate

Others

  • Obeticholic acid, fibrates, leukotriene antagonists, antiretrovirals, Mycophenolate mofetil, molecular therapies, monoclonal antibodies are promising therapies that are currently being studied
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