What is the management and treatment of primary biliary cirrhosis?

Management and Treatment of Primary Biliary Cirrhosis

Ursodeoxycholic acid (UDCA) is the first-line treatment for primary biliary cirrhosis (PBC) at a dose of 13-15 mg/kg/day, with obeticholic acid as a second-line therapy for patients with inadequate response to UDCA or who cannot tolerate it. 1, 2

First-Line Treatment

• UDCA at 13-15 mg/kg/day is the cornerstone of PBC treatment, with evidence showing it delays histological progression to cirrhosis and improves biochemical markers of cholestasis 2, 3
• When administered at appropriate doses, a majority of patients with PBC can achieve a normal life expectancy without additional therapeutic measures 2
• UDCA should be continued long-term, as studies demonstrate that 6.6 years of therapy significantly reduces progression to cirrhosis (13% vs 49% in controls) 3
• UDCA is considered safe during pregnancy and should be continued peri-conception, peri-partum, and post-partum in women of reproductive age 1

Second-Line Therapy

• Obeticholic acid (OCALIVA) is FDA-approved for adult patients with PBC without cirrhosis or with compensated cirrhosis who do not have evidence of portal hypertension, either:
  • In combination with UDCA in patients with inadequate response to UDCA, or
  • As monotherapy in patients unable to tolerate UDCA 4
• Starting dose is 5 mg once daily for the first 3 months, with potential increase to 10 mg daily if inadequate response and good tolerability 4
• IMPORTANT: Obeticholic acid carries a boxed warning for hepatic decompensation and failure in PBC patients with cirrhosis 4
• Obeticholic acid is contraindicated in patients with:
  • Decompensated cirrhosis (Child-Pugh Class B or C)
  • Prior decompensation events
  • Compensated cirrhosis with evidence of portal hypertension
  • Complete biliary obstruction 4

Monitoring and Response Assessment

• Routinely monitor patients during treatment for:
  • Biochemical response (liver function tests)
  • Tolerability
  • Disease progression 1
• Non-responders to treatment who did not have advanced disease at presentation require life-long follow-up with annual monitoring for progression (ultrasound, transient elastography, routine blood tests) 1
• Patients with mild disease and near-normal liver biochemistry tests require less intensive follow-up with yearly liver function tests 1
• Bilirubin >50 μmol/L is a predictor of adverse outcome; such patients should be discussed with a hepatologist experienced in managing advanced disease 1

Management of Complications

Pruritus

• Add bile acid binding resins (cholestyramine) or antihistamines 1
• Rifampicin (second trimester onwards in pregnancy) is considered safe 1
• For obeticholic acid-related pruritus: reduce dosage, temporarily interrupt dosing, or add antihistamines/bile acid binding resins 4
• In severe cases during pregnancy, plasmapheresis may be considered 1

Portal Hypertension and Cirrhosis

• Screen for varices according to standard guidelines for cirrhotic patients 1
• Patients with liver stiffness <20 kPa and platelet count >150,000 are at very low risk of having varices requiring treatment 1
• Annual assessment using transient elastography and platelet count should be considered 1
• Manage ascites according to current guidelines for portal hypertension 1
• Consider transjugular intrahepatic portosystemic shunt (TIPS) for patients with variceal bleeding that fails to respond to endoscopic or pharmacological therapy 1

Sicca Complex

• Artificial tears and saliva are often helpful for symptoms of dry eyes and mouth 1
• Pilocarpine or cevimeline (muscarinic receptor agonists) can be used for refractory symptoms 1
• Provide oral hygiene advice to prevent dental caries in patients with severe xerostomia 1
• Monitor for oral candidiasis in patients with severe xerostomia 1

Special Populations

Pregnancy

• PBC is typically well-tolerated in non-cirrhotic patients, though pruritus may worsen 1
• Continue UDCA during pregnancy, as expert opinion considers it safe 1
• Pregnant patients with portal hypertension should be electively endoscoped in the second trimester 1
• Screen pregnant PBC patients for anti-Ro and anti-La antibodies, as their presence would affect obstetric management 1

PBC/AIH Overlap Syndrome

• True overlap with autoimmune hepatitis is rare and requires liver biopsy with expert clinicopathological review for diagnosis 1
• Consider liver biopsy in patients with marked hepatitic activity (transaminases >5x ULN) and elevated IgG concentrations 1
• Severe interface hepatitis in the appropriate context may warrant immunosuppressive therapy after discussing risks and benefits with the patient 1

Liver Transplantation

• Consider liver transplantation for patients with:
  • Bilirubin >50 μmol/L (including those treated with UDCA)
  • Evidence of decompensated liver disease 1
• Discuss transplantation with a hepatologist linked to a liver transplant program 1

Hepatocellular Carcinoma Screening

• 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
• Screening should follow international guidelines for cirrhotic patients 1

Family Screening

• Relatives of patients with PBC do not need to be routinely screened for PBC 1
• The prevalence of PBC among daughters of mothers with the disease is approximately 2% 1
• Formal screening is not recommended due to the low likelihood of positive results and potential insurance implications 1