Primary Biliary Cholangitis

Essentials

• Primary biliary cholangitis (PBC) is a chronic cholestatic disease with unknown aetiology characterized by inflammation that damages small bile ducts.
• PBC belongs to the group of autoimmune liver diseases.
• At the time of diagnosis the patients often have only few symptoms. Investigations are started because of increased alkaline phosphatase (ALP) concentration.
• Large increase in bilirubin concentration is a sign of active or advanced disease.

Epidemiology

• Incidence is 0.2-5.8 new cases/100 000 population, prevalence 10-50/100 000 population.
• 90% of the patients are women.
• The age of onset is (20-)40-60(-70) years.

Symptoms and signs

• The typical patient is a middle-aged woman with no or only few symptoms.
• Abnormal ALP concentration is incidentally detected.
• Possible symptoms include itch, jaundice and hepatomegaly.
  • Generalized itch, initially only in the evening, is usually the presenting symptom. The itch may appear during the use of oestrogens or drugs causing cholestasis, and sometimes in association with pregnancy.
  • Jaundice is the presenting symptom in 10% of the patients.
  • Hepatomegaly is detected in 50% of the patients on presentation.
• Splenomegaly, xanthelasmas, or cirrhosis of the liver is detected in some patients already on presentation.
• Non-specific symptoms include fatigue, articular symptoms, and dry mouth or eyes.
• Osteoporosis Osteoporosis is common in advanced disease.

Investigations

• See Assessing a patient with an abnormal liver function test result Assessing a Patient with an Abnormal Liver Function Test Result.
• Basic laboratory investigations
  • ESR is usually increased.
  • Cholesterol and bile acid concentrations are increased in a more severe disease.
• Plasma ALP concentration is often markedly increased. ALT may be mildly increased.
• GT concentration may be increased. Bilirubin only increases as the disease progresses.
• If only ALP concentration is increased, the ALP isoenzyme test should be performed.
• Testing for autoimmune liver disease: anti-smooth muscle antibodies, anti-mitochondrial antibodies, IgG, IgM
  • Anti-mitochondial antibodies are detected in 95% of the patients.
  • Serum IgM is increased in 80% of the patients.
• Liver imaging
  • Ultrasonography finding may be normal, or cirrhosis-type findings are detected (keep in mind also other aetiologies).
  • MR cholangiography is sometimes useful in differential diagnosis (ruling out primary sclerosing cholangitis [PSC]).
• Other cholestatic liver diseases should be considered in differential diagnosis.

Diagnosis

• An increased ALP and positiveantimitochondrial antibodies are sufficient for diagnosis.
• With the help of elastography (e.g. Fibroscan^® ), the amount of developed fibrosis can be assessed (whether there is something suggesting chirrhosis).
• Indications for liver biopsy
  • Aim to exclude other liver diseases, e.g. suspected mixed autoimmune liver disease (overlapping autoimmune hepatitis or primary sclerosing cholangitis Primary Sclerosing Cholangitis)
  • Treatment response remains inadequate.
  • Aim to assess the degree of liver damage in an unclear situation

Treatment

• Treatment and follow-up are performed in specialized care.
• No medication has been definitely shown to slow the progression of the disease. Ursodeoxycholic acid (UDCA; 13-15 mg/day) given in early disease improves laboratory parameters and probably postpones the development of cirrhosis and the need for liver transplantation, but there is insufficient evidence of its effect on long-term prognosis Ursodeoxycholic Acid in the Treatment of Primary Biliary Cirrhosis.
• Budesonide (6-9 mg/day) combined with ursodeoxycholic acid sometimes helps in problematic cases (poor treatment response to ursodeoxycholic acid, substantial inflammatory findings at histology but no cirrhotic liver damage).
• Fibrates (pheno- andbezafibrate) are combined with ursodeoxycholic acid if the treatment response as monotherapy is inadequate.
• The itch can be treated with antihistamines, rifampicin or cholestyramine.
• Calcium and vitamin D should be taken in sufficient amounts to prevent bone affection.
• Osteoporosis can be treated with bisphosphonates or an oestrogen preparation in the postmenopausal years.
• Hypercholesterolaemia is treated if there are risk factors for cardiovascular diseases.
• Liver transplantation may be required due to complications of PBC (liver failure, recurring variceal bleeding, difficult-to-manage ascites) or cholestasis-related unbearable itch, etc., usually not earlier than at the age of 60 to 65 years.

• The frequency of follow-up checks is determined by the severity of the liver disease.
  • Liver function tests etc. every 3 to 12 months
  • Liver ultrasonography every 1 to 3 years

Prognosis

• The course of the disease is better predicted than in most other cirrhoses. Increased bilirubin concentration is a sign of poor prognosis.
• After the patient has become symptomatic, life-expectancy without liver transplantation is 5-10 years.