What are the investigations and treatment for autoimmune hepatitis?

Investigations and Treatment for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis (AIH) requires a combination of laboratory tests, immunological markers, and liver biopsy, with treatment consisting primarily of prednisone and azathioprine as first-line therapy. 1

Diagnostic Investigations

Laboratory Tests

• Liver Function Tests:
  • Elevated transaminases (AST/ALT)
  • ALP:AST (or ALT) ratio <1.5 (+2 points in diagnostic criteria) 1
  • Serum immunoglobulin G (IgG) elevated in 90% of cases 1

Immunological Markers

• First-line autoantibody testing by indirect immunofluorescence:
  • Antinuclear antibodies (ANA): present in 75-95% of AIH-1
  • Smooth muscle antibodies (SMA): present in up to 75% of AIH-1
  • Anti-liver kidney microsome type 1 (anti-LKM1): present in 70% of AIH-2
  • Anti-liver cytosol type 1 (anti-LC1): present in 30% of AIH-2 1

Histological Assessment

• Liver biopsy is essential for definitive diagnosis 1
• Key histological features:
  • Interface hepatitis (+3 points in diagnostic criteria)
  • Predominantly lymphoplasmacytic infiltrate (+1 point)
  • Rosetting of liver cells (+1 point) 1
  • Portal plasma cell infiltration 2

Exclusion of Other Conditions

• Viral hepatitis markers (negative markers give +3 points)
• Wilson disease
• Alpha-1 antitrypsin deficiency
• Drug-induced liver injury
• Alcoholic liver disease
• Non-alcoholic fatty liver disease
• Primary biliary cholangitis
• Primary sclerosing cholangitis 1

Diagnostic Scoring Systems

• Validated scoring systems:
  • Original Revised Scoring System (1999): ≥15 points for definite AIH, 10-15 points for probable AIH
  • Simplified Scoring System (2008): ≥7 points for definite AIH, ≥6 points for probable AIH 1, 3

Treatment

Indications for Treatment

• Treatment should be initiated for:
  • Moderate to severe inflammation (AST/ALT >5× upper limit of normal)
  • Serum globulins >2× upper limit of normal
  • Liver biopsy showing confluent necrosis
  • Young patients
  • Symptomatic patients
  • Patients with cirrhosis, even with mild histological activity 1

First-Line Therapy

• Combination therapy with prednisone and azathioprine is recommended:
  • Fewer corticosteroid-related side effects (10% versus 44% with prednisone alone) 1
  • For adults: Initial prednisone dose with gradual tapering to maintenance level
  • For children: High-dose prednisone (1-2 mg/kg daily) for up to 2 weeks, then gradual decrease to maintenance level (0.1-0.2 mg/kg daily or 5 mg daily) within 6-8 weeks 2

Treatment Goals and Duration

• Treatment endpoint: Resolution of laboratory indices (normal serum AST/ALT, γ-globulin, and IgG levels) and tissue manifestations of active liver inflammation 2
• Average treatment duration: 18-24 months 2
• Liver biopsy prior to treatment termination is recommended to ensure full resolution 2
• Treatment should be considered for termination after at least 2 years when liver function tests and immunoglobulin levels have been repeatedly normal 2

Management of Incomplete Response

• For patients who improve but don't achieve complete resolution after 36 months (13% of patients):
  • Long-term low dose corticosteroid therapy (gradual decrease to 10 mg daily)
  • Long-term azathioprine (2 mg/kg daily) for corticosteroid-intolerant individuals 2

Monitoring and Follow-up

• Regular assessment of transaminases and IgG levels
• Bone mineral densitometry at baseline and annually for patients on long-term corticosteroids
• HCC screening with liver ultrasound every 6 months in cirrhotic patients
• All children should undergo MR cholangiography to exclude autoimmune sclerosing cholangitis 1

Special Considerations and Pitfalls

Atypical Presentations

• Acute severe (fulminant) AIH may require modified treatment approaches 1
• Diagnostic uncertainty may require a short (≤2 weeks) treatment trial with corticosteroids 1
• AIH may overlap with primary biliary cholangitis or primary sclerosing cholangitis 1

Common Pitfalls

1. Misdiagnosis: AIH can be challenging to diagnose due to heterogeneous clinical, serological, and pathological features 4
2. Incomplete treatment: Titrations in dose are associated with delayed or incomplete histological improvement 2
3. Premature treatment discontinuation: Interface hepatitis is found in 55% of patients with normal serum AST and γ-globulin levels during therapy, and these individuals typically relapse after cessation of treatment 2
4. Inadequate monitoring: Normalization of tests and tissue does not protect against relapse, and 60% of patients who relapse do so despite disappearance of inflammatory features 2

Drug Toxicity

• Drug toxicity justifies premature discontinuation or alteration of conventional therapy in 13% of patients
• In these instances, therapy with the tolerated agent (prednisone or azathioprine) can be maintained in adjusted dose 2

By following this comprehensive diagnostic and treatment approach, most patients with AIH can achieve remission and maintain a near-normal life expectancy with appropriate management.