What is the most appropriate next step in management for a patient with autoimmune hepatitis, Systemic Lupus Erythematosus (SLE) on hydroxychloroquine, and Non-Alcoholic Fatty Liver Disease (NAFLD) components, presenting with jaundice, pruritis, and abnormal liver function tests?

Management of Autoimmune Hepatitis in a Patient with SLE

This patient requires immediate initiation of prednisolone-based immunosuppressive therapy (Option A) for definite autoimmune hepatitis, as confirmed by interface hepatitis with plasma cells on liver biopsy, elevated transaminases, hyperglobulinemia, and positive ANA. 1

Diagnostic Confirmation

This patient meets definite criteria for autoimmune hepatitis based on:

• Histological findings: Interface hepatitis with plasma cells is the hallmark pathological feature of AIH 2
• Biochemical markers: Markedly elevated AST (654 IU/L) and ALT (734 IU/L) with elevated globulin (43 g/L) 2
• Serological evidence: ANA titer of 1:640 (≥1:80 adds 2 points to simplified diagnostic criteria) 2
• Exclusion of viral hepatitis: Negative viral markers add 2 points to diagnostic scoring 2

The simplified diagnostic score totals ≥7 points (definite AIH): ANA ≥1:80 (2 points), IgG/globulin elevation (2 points), typical histology with interface hepatitis and plasma cells (2 points), and negative viral markers (2 points). 2

Why Prednisolone is the Correct Choice

Standard first-line therapy for AIH consists of corticosteroids with or without azathioprine. 1 The European Association for the Study of the Liver explicitly recommends treating AIH with standard immunosuppressive therapy consisting of corticosteroids, regardless of serological status, when interface hepatitis and lymphoplasmacytic infiltration are present on biopsy. 1

Initial Treatment Regimen

• Start prednisolone 30 mg daily with azathioprine 50 mg daily as combination induction therapy 1
• Target normalization of transaminases and immunoglobulins within 6-12 months 2, 1
• Monitor complete blood count and liver function tests weekly for the first 4 weeks 3
• Check TPMT activity before initiating azathioprine to avoid severe myelosuppression 3

Why NOT Methotrexate (Option B)

Methotrexate is not a standard treatment for AIH and is actually contraindicated:

• Methotrexate can cause hepatotoxicity and is not recommended in established liver disease 2
• No guideline recommends methotrexate as first-line therapy for AIH 2
• The patient already has significant hepatic inflammation (AST/ALT >15x normal), making methotrexate particularly inappropriate

Why NOT Vitamin E with Weight Loss (Option C)

While this patient has features suggesting NAFLD (obesity, bright coarse echogenicity on ultrasound, elevated random glucose), treating the NAFLD component without addressing the active autoimmune hepatitis would be catastrophic:

• Untreated AIH progresses to cirrhosis and liver failure with high mortality 4
• The degree of transaminase elevation (AST 654, ALT 734) far exceeds typical NAFLD and indicates severe active inflammation requiring immediate immunosuppression 2
• Vitamin E is appropriate for NASH but has no role in treating AIH 2
• The interface hepatitis with plasma cells on biopsy is pathognomonic for AIH, not NAFLD 2

Special Considerations for SLE Overlap

This patient's concurrent SLE on hydroxychloroquine requires specific attention:

• Distinguish AIH from lupus hepatitis: The presence of interface hepatitis with prominent plasma cells, markedly elevated transaminases (>10x ULN), and high globulin favor AIH over lupus hepatitis 5, 6
• Lupus hepatitis typically shows predominant lymphoid infiltrates with lobular inflammation rather than interface hepatitis 5
• Both conditions respond to corticosteroids, making prednisolone appropriate regardless 5, 6
• Continue hydroxychloroquine as it does not interfere with AIH treatment 5

Treatment Monitoring and Endpoints

Complete biochemical response is defined as normalization of serum transaminases and IgG within 6 months of treatment initiation. 2

Monitoring Schedule:

• Weekly CBC and LFTs for first 4 weeks 3
• Every 2-4 weeks during dose adjustments 1
• Every 3 months minimum after achieving stable maintenance therapy 1

Dose Tapering Strategy:

• Begin tapering prednisolone after biochemical improvement, reducing by 2.5-5 mg every 2-4 weeks 1
• Increase azathioprine to 2 mg/kg daily as prednisone is tapered 1, 3
• Target azathioprine monotherapy for long-term maintenance 3

Critical Pitfalls to Avoid

• Do not delay treatment waiting for additional serological testing—the biopsy showing interface hepatitis with plasma cells is diagnostic 2, 1
• Do not attribute liver disease solely to NAFLD when interface hepatitis is present on biopsy 2
• Do not use methotrexate in patients with active liver disease 2
• Do not stop treatment prematurely—AIH requires long-term, often lifelong maintenance therapy to prevent relapse 2, 3
• Monitor for azathioprine toxicity including myelosuppression and cholestatic hepatitis 7, 3

Prognosis with Treatment

With appropriate immunosuppressive therapy, 87% of patients achieve remission over a median follow-up of 67 months, with 94% showing inactive or minimal histological disease on follow-up liver biopsy. 3 Untreated AIH, however, progresses to cirrhosis and has significantly increased mortality. 4