What is the management and treatment of primary biliary cirrhosis?

Management and Treatment of Primary Biliary Cholangitis (PBC)

Start all PBC patients without cirrhosis or with compensated cirrhosis (who lack portal hypertension) on ursodeoxycholic acid (UDCA) 13-15 mg/kg/day as first-line therapy, which delays histological progression to cirrhosis and improves survival. 1, 2

First-Line Treatment: UDCA

• UDCA at 13-15 mg/kg/day is the cornerstone of PBC treatment, with evidence demonstrating delayed progression to cirrhosis and improved biochemical markers of cholestasis 1, 2
• Continue UDCA indefinitely, including during pregnancy and breastfeeding, as it is considered safe in these settings 1, 3
• Monitor patients routinely during treatment for biochemical response, tolerability, and disease progression 1

Response Assessment After UDCA Initiation

• Assess biochemical response after at least 1 year of UDCA therapy at appropriate dosing 4
• Non-responders require lifelong follow-up with annual monitoring for evidence of progression using ultrasound, transient elastography, and routine blood tests 5, 1
• Patients with mild disease and near-normal liver biochemistry require less intensive follow-up with yearly liver function tests 1

Second-Line Therapy for Inadequate UDCA Response

For patients with inadequate biochemical response to UDCA after 1 year, add obeticholic acid starting at 5 mg once daily for 3 months, then increase to 10 mg once daily if tolerated and needed. 4

Critical Contraindications for Obeticholic Acid

• Absolutely contraindicated in patients with:
  • Decompensated cirrhosis (Child-Pugh Class B or C) 1, 4
  • Prior decompensation events 1, 4
  • Compensated cirrhosis with evidence of portal hypertension (ascites, gastroesophageal varices, persistent thrombocytopenia) 1, 4
  • Complete biliary obstruction 4

Monitoring During Obeticholic Acid Treatment

• Closely monitor patients with compensated cirrhosis for new evidence of portal hypertension (ascites, varices, thrombocytopenia) or increases in total bilirubin, direct bilirubin, or prothrombin time 4
• Permanently discontinue obeticholic acid if patients develop:
  • Laboratory or clinical evidence of hepatic decompensation 4
  • Evidence of portal hypertension in compensated cirrhosis 4
  • Clinically significant hepatic adverse reactions 4

Management of Symptoms and Complications

Pruritus Management

• Add bile acid binding resins or antihistamines as first-line adjunctive therapy for pruritus 1, 4
• For refractory symptoms, use pilocarpine or cevimeline (muscarinic receptor agonists) 5, 1
• Rifampicin is safe during pregnancy for severe pruritus 1
• Consider plasmapheresis in severe cases during pregnancy 1
• For intolerable pruritus on obeticholic acid, reduce dosage to 5 mg every other day or temporarily interrupt dosing for up to 2 weeks 4

Sicca Complex (Dry Eyes/Mouth)

• Artificial tears and saliva are first-line treatments 5, 1
• Use pilocarpine or cevimeline for refractory symptoms 5, 1
• Provide oral hygiene advice to prevent dental caries in severe xerostomia 5, 1
• Monitor for oral candidiasis in patients with severe xerostomia 5, 1
• Vaginal moisturizers may be helpful; oestrogen creams can be used without hepatology concerns 5

Fatigue and Psychological Support

• Assess all patients for depression, as social isolation, fatigue, anxiety and depression predict poor quality of life 5
• Consider trial of antidepressants where appropriate 5
• Implement pacing strategies (using available energy optimally) and timing strategies (scheduling key tasks earlier in the day when fatigue is less severe) 5
• Modafinil may be considered for severe daytime somnolence with associated fatigue 5

Identifying and Managing Advanced Liver Disease

Cirrhosis Detection

Use a combination of clinical markers to identify cirrhosis:

• Liver biopsy confirmation (though can be falsely reassuring due to patchy disease) 5
• Radiological findings: nodular liver with enlarged spleen 5
• History of complications: ascites, variceal bleeding, encephalopathy, bacterial peritonitis 5
• Laboratory findings: low platelets, low albumin, prolonged PT/INR 5
• Vibration-controlled transient elastography (VCTE) is one of the best surrogate markers for detecting cirrhosis or severe fibrosis 5

Variceal Screening

• Patients with liver stiffness <20 kPa and platelet count >150,000 are at very low risk of varices requiring treatment 1
• Screen for varices according to standard guidelines for cirrhotic patients 1
• Consider annual assessment using transient elastography and platelet count 1

Portal Hypertension Management

• Manage ascites according to current portal hypertension guidelines 1
• Consider transjugular intrahepatic portosystemic shunt (TIPS) for variceal bleeding failing endoscopic or pharmacological therapy 1

High-Risk Patients Requiring Specialist Referral

• Patients with bilirubin >50 μmol/L should be discussed with a hepatologist experienced in managing advanced disease, as this predicts adverse outcomes 1
• Refer patients with symptoms resistant to medical therapy for specialist management regardless of disease severity 5
• Consider liver transplantation for patients with bilirubin >50 μmol/L or evidence of decompensated liver disease 1

Special Populations

Pregnancy

• PBC is typically well-tolerated in non-cirrhotic patients, though pruritus may worsen 1, 3
• Continue UDCA throughout pregnancy, peri-conception, peri-partum, and post-partum 1, 3
• Discontinue obeticholic acid during pregnancy and breastfeeding 3
• Pregnant patients with portal hypertension should be electively endoscoped in the second trimester 1, 3
• Screen pregnant PBC patients for anti-Ro and anti-La antibodies, as their presence affects obstetric management 1

PBC/Autoimmune Hepatitis Overlap

• True overlap is rare and requires liver biopsy with expert clinicopathological review 1
• Consider liver biopsy in patients with marked hepatitic activity and elevated IgG concentrations 1
• Severe interface hepatitis may warrant immunosuppressive therapy after discussing risks and benefits 1

Hepatocellular Carcinoma Surveillance

• Patients with PBC who have cirrhosis are at increased risk of hepatocellular carcinoma 1
• Non-responders to treatment and male patients are at greater risk 1
• Screen according to international guidelines for cirrhotic patients 1

Common Pitfalls to Avoid

• Never use obeticholic acid in patients with any evidence of portal hypertension or decompensated cirrhosis - this can be fatal 4
• Do not assume liver biopsy rules out cirrhosis in PBC, as disease severity is patchy within the liver 5
• When using bile acid binding resins or rifampicin, monitor for vitamin K deficiency and consider supplementation 3
• Take obeticholic acid at least 4 hours before or after bile acid binding resins to avoid interaction 4
• Do not routinely screen relatives of PBC patients, as prevalence among daughters is only approximately 2% 1