What is the recommended treatment regimen for autoimmune cholangitis, including first‑line therapy, second‑line options, management of autoimmune hepatitis overlap, monitoring, and criteria for liver transplantation?

Treatment of Autoimmune Cholangitis

Autoimmune cholangitis (also known as AMA-negative PBC or autoimmune cholangiopathy) should be treated with ursodeoxycholic acid (UDCA) at 13-15 mg/kg/day as first-line therapy, identical to the approach for primary biliary cholangitis. 1, 2, 3

First-Line Therapy: UDCA

• UDCA at 13-15 mg/kg/day is the cornerstone of treatment, administered either as a single daily dose or divided into 2-3 doses throughout the day—both regimens achieve equivalent biliary enrichment and biochemical improvement. 1, 2, 3, 4

• UDCA significantly reduces serum bilirubin, alkaline phosphatase, GGT, and cholesterol levels while delaying histological progression when initiated early in disease. 3

• Long-term UDCA therapy reduces the likelihood of liver transplantation or death in patients with moderate to severe disease. 3

Assessment of Treatment Response

• Biochemical response must be evaluated after 12 months of UDCA therapy using validated risk stratification tools such as the GLOBE Score or UK-PBC Risk Score to identify patients at risk for disease progression. 1, 3

• Response assessment should document changes in alkaline phosphatase, bilirubin, and transaminases compared to baseline values. 1, 3

Management of Overlap with Autoimmune Hepatitis

If features of autoimmune hepatitis coexist (elevated transaminases >5x ULN, elevated IgG, interface hepatitis on biopsy), combination therapy is mandatory:

• Continue UDCA at 13-15 mg/kg/day for the cholestatic component. 1, 2

• Add prednisolone 0.5 mg/kg/day (tapered to 10-15 mg/day maintenance) plus azathioprine 50-75 mg/day for the hepatitic component. 1, 2

• The AIH component requires immunosuppression to prevent progression—UDCA monotherapy is inadequate and should never be used alone in overlap syndromes. 2

• Liver biopsy with expert clinicopathological assessment is recommended when overlap syndrome is suspected, as this diagnosis should not be made on biochemical grounds alone. 1, 2

Symptom Management

• UDCA does not improve pruritus, which affects quality of life significantly in cholestatic diseases. 3

• For severe pruritus, initiate sertraline (SSRI) as first-line pharmacotherapy, with rifampicin as second-line treatment. 3

• Bile acid sequestrants and opioid antagonists serve as additional options for refractory pruritus. 3

• Fatigue should be documented annually using validated symptom scales, and patients with profound psychological distress should be referred for cognitive behavioral therapy. 1, 3

Monitoring Protocol

Regular monitoring should include:

• Liver biochemistry every 3-6 months to assess treatment response and disease progression. 1, 3

• Annual documentation of fatigue and pruritus severity using validated scales. 1, 3

• Osteoporosis risk assessment within 5 years of diagnosis using DEXA scan or FRAX score, as cholestatic liver disease significantly increases fracture risk. 1, 3

• Abdominal ultrasound at baseline to exclude alternative causes of cholestasis and assess for focal liver lesions. 1, 3

Criteria for Liver Transplantation Referral

Refer to transplant hepatology when:

• Serum bilirubin exceeds 50 μmol/L (approximately 3 mg/dL). 1, 3

• Any evidence of decompensated liver disease develops (ascites, variceal bleeding, hepatic encephalopathy). 1, 3

• Intractable pruritus severely impairs quality of life despite maximal medical therapy. 1

• Recurrent bacterial cholangitis occurs in the setting of advanced disease. 1

Post-Transplant Management

• UDCA should be administered lifelong at 10-15 mg/kg/day in two divided doses after liver transplantation to prevent disease recurrence. 1, 3

• Post-transplant UDCA reduces the risk of disease recurrence and improves graft survival and long-term overall survival. 1, 3

• Corticosteroid withdrawal should be performed cautiously in patients with autoimmune features due to risk of disease recurrence. 1

Critical Pitfalls to Avoid

• Never use high-dose UDCA (>15 mg/kg/day), as doses of 28-30 mg/kg have been associated with increased serious adverse events, death, liver transplantation, and variceal development in cholestatic diseases. 2

• Do not rely solely on serum UDCA levels to assess treatment response—biochemical improvement correlates with biliary enrichment, not serum concentrations. 4

• Avoid delaying immunosuppression in overlap syndromes while waiting for UDCA response, as the hepatitic component will progress without corticosteroids. 1, 2

• Do not assume normal alkaline phosphatase excludes significant disease—transaminases may be more elevated than alkaline phosphatase in overlap syndromes. 1