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.


 

Monitoring

Annual Re-evaluation for Certain Patients

  • Patients positive for AMA, but have a normal ALP level, should have their liver biochemistry rechecked yearly
  • A small study has shown that most AMA-positive asymptomatic individuals with normal ALP eventually develop evidence of cholestasis and/or cholestatic symptoms after several years

Prevention and Treatment of Complications

  • Patients with cirrhosis and inadequate biochemical response to treatment [ie diagnosed at early age (eg <45 years), presented with advanced disease stage] have a high risk of developing PBC complications 
  • Assess PBC activity and progression with tests for albumin, total bilirubin, AST, ALT, ALP, GGT, PT every 3-6 months
  • Assess esophageal/gastric varices complication with an upper gastrointestinal endoscopy annually and liver cirrhosis with an abdominal US with or without serum alpha-fetoprotein every 6 months

Fatigue

  • As there is currently no recommended therapy for fatigue, patient education and counseling regarding this symptom is important 
  • Determine and treat other causes of fatigue, eg anemia, hypothyroidism, sleep disorders

Pruritus

  • Pruritus has a significant effect on a patient’s life and is often refractory to medical treatment
  • Lifestyle changes such as avoidance of itchy or tight clothes and use of moisturizers or emollients, tepid baths, or ice packs may be helpful

Cholestyramine

  • Cholestyramine is the main drug used to treat cholestasis-associated pruritus
  • Action: Binds bile acids in the gut lumen promoting its fecal excretion
  • Most effective in patients with intact gallbladders if taken before and after breakfast, because this is when the largest amount of bile is available for binding by the drug
  • Drug takes effect within 1-4 days of starting therapy
  • Effect is optimal with daily treatment
  • Given 2-4 hours before or after other medications because Cholestyramine can also bind other oral drugs 
  • Patients unresponsive to Cholestyramine can be given Rifampicin, opioid antagonists eg Naltrexone and Naloxone, or Sertraline

Antihistamines

  • May be used to control mild pruritus early in the course of the disease
    • Should be used with caution in patients with cirrhosis or signs of encephalopathy because antihistamines can depress brain function further
  • Not typically very effective and most of the relief results from sedation

Others

  • Other medications for the treatment of pruritus are Rifaximin, Dronabinol, Phenobarbital and Metronidazole
  • Newer agents include a peroxisome proliferator activator receptor (PPAR) agonists, autotaxin inhibitors and ileal bile acid reabsorption transporter inhibitors

Portal Hypertension

  • Portal hypertension may develop earlier than cirrhosis from nodular regenerative hyperplasia
  • Nonselective beta-blockers may help relieve portal hypertension
  • Patients may also benefit from shunt surgery
  • Patients should be screened endoscopically for varices upon diagnosis of PBC and every 3 years thereafter
  • Prophylactic measures to prevent bleeding should be carried out in patients with varices

Metabolic Bone Disease

  • Osteoporosis is often subtle and can only be detected by measuring bone mineral density using dual energy X-ray absorptiometry (DEXA)
  • Patient’s bone mineral density should be assessed at the time of diagnosis of PBC and every 1-2 years thereafter
  • All PBC patients should be advised to engage in regular weight-bearing exercise and if required, to stop smoking and drinking alcohol
  • Vitamin D and calcium supplementation should be given 
  • In patients with evidence of osteoporosis, bisphosphonates are of benefit
  • Estrogen hormone replacement therapy may be needed in certain patients
    • Transdermal administration may be the preferred route

Sicca Syndrome

  • Symptoms of the sicca syndrome should be elicited by direct questioning
  • Patients with dry eyes should be given artificial tears initially to prevent complications eg corneal ulceration
    • Ciclosporin or Lifitegrast can be used in patients unresponsive to other therapies 
  • Patients with dry mouth should be given saliva substitutes and undergo monitoring of oral health
  • Pilocarpine or Cevimeline can be given to patients with dry mouth or dry eyes who are unresponsive to other therapies
  • Liquids should be given with food and medications to ease swallowing
  • Lubricating jelly and moisturizers may be used in female patients with dyspareunia

Malabsorption of Fat-Soluble Vitamins

  • Replacement of fat-soluble vitamins (eg vitamin K) may be given using their parenteral or water-soluble forms
  • If bilirubin level is >2 mg/dL, monitor vitamins A, D, E and prothrombin time yearly

Hyperlipidemia

  • A complication of chronic cholestasis, hyperlipidemia seen in PBC is apparently not associated with increased risk of cardiovascular disease
  • Statins and fibrates may be given to patients with PBC 
    • Fibrates may occasionally cause a paradoxical increase in serum cholesterol levels

Thyroid Dysfunction

  • Thyroid-stimulating hormone should be determined at the time of diagnosis of PBC and regularly thereafter ie yearly

Raynaud’s Syndrome

  • More of an issue for patients in cold climates
  • Patient should be advised to avoid exposure of extremities to cold and to stop smoking
  • Calcium antagonists may relieve extremity symptoms but may worsen esophageal dysmotility
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