Can Budesonide be used to treat cholestatic drug-induced liver injury with normal autoimmune markers and Immunoglobulin G (IgG) levels?

Budesonide Should NOT Be Used for Cholestatic Drug-Induced Liver Injury with Normal Autoimmune Markers

Budesonide is contraindicated in cholestatic drug-induced liver injury (DILI) with normal autoimmune markers and IgG levels, as corticosteroids and immunosuppressive therapy are not recommended for cholestatic DILI without autoimmune features. 1

Rationale Against Budesonide Use

Primary Management Strategy

• The only effective treatment for cholestatic DILI is immediate withdrawal of the suspected drug 1, 2
• Early detection and prompt drug discontinuation are crucial for favorable outcomes 1
• Cholestatic DILI generally has a better prognosis than hepatocellular injury when the offending drug is stopped 1

Why Corticosteroids Are Not Indicated

Corticosteroids, including budesonide, should only be considered in DILI cases with autoimmune features, specifically when:

• IgG levels are elevated >2× ULN, AND/OR
• Anti-smooth muscle antibody titers are >1:80 1, 3

Your case explicitly states normal autoimmune markers and normal IgG levels, which excludes the indication for any corticosteroid therapy 1

Specific Contraindications for Budesonide in Cholestatic Disease

• Budesonide has 90% first-pass hepatic metabolism and should NOT be used in patients with cirrhosis or portal hypertension due to risk of systemic side effects when first-pass metabolism is impaired 3
• Budesonide is specifically indicated only for non-cirrhotic autoimmune hepatitis patients, not for cholestatic DILI 3
• Portal vein thrombosis has been reported with budesonide use in advanced cholestatic liver disease 3

Recommended Treatment Approach

First-Line Management

1. Immediately discontinue the suspected causative drug 1, 2
2. Repeat liver function tests within 7-10 days to confirm cholestatic pattern (alkaline phosphatase >2× ULN or ALT/AP ratio <2) 1
3. Continue monitoring until alkaline phosphatase normalizes, total bilirubin normalizes, and clinical symptoms resolve 1

Adjunctive Therapy Consideration

• Ursodeoxycholic acid (UDCA) 13-15 mg/kg/day may be considered as it beneficially affects cholestasis in approximately two-thirds of cases, though evidence is limited 1, 4
• UDCA is the only pharmacologic adjunct with any supporting evidence for cholestatic DILI 1

Critical Distinction: Drug-Induced Autoimmune-Like Hepatitis

You must differentiate cholestatic DILI from drug-induced autoimmune-like hepatitis, which presents differently:

• Aminotransferases typically >5× ULN (not just cholestatic pattern) 1, 3
• Positive autoantibodies (ANA, anti-smooth muscle antibody) 3, 5
• Elevated IgG levels 3, 5
• Interface hepatitis with prominent plasma cell infiltrate on biopsy 5

Only drug-induced autoimmune-like hepatitis may warrant corticosteroid therapy 5, 6, and even then, complete resolution after drug withdrawal without recurrence distinguishes it from true autoimmune hepatitis 5

Common Pitfall to Avoid

Do not confuse cholestatic DILI with overlap syndromes or autoimmune hepatitis 1. The presence of normal autoimmune markers and normal IgG in your case definitively excludes autoimmune features that would justify immunosuppressive therapy 1, 3. Using budesonide inappropriately could expose the patient to unnecessary risks including metabolic side effects, infection risk, and in advanced disease, portal vein thrombosis 3.