What are the diagnostic criteria and first-line treatment for autoimmune hepatitis?

Autoimmune Hepatitis: Diagnostic Criteria and First-Line Treatment

Diagnose autoimmune hepatitis using a combination of elevated aminotransferases, hypergammaglobulinemia (IgG ≥1.5 times normal), positive autoantibodies (ANA, SMA, or anti-LKM1 ≥1:80 in adults), interface hepatitis on liver biopsy, and exclusion of viral hepatitis, drug toxicity, and genetic liver diseases—then treat all patients with moderate to severe disease using corticosteroids combined with azathioprine as first-line therapy. 1, 2

Diagnostic Approach

Essential Laboratory Testing

Begin with the following serological panel:

• Autoantibodies: Test ANA and SMA simultaneously as the initial screen; if both are negative, add anti-LKM1 testing 1

  • Type 1 AIH: ANA and/or SMA positive (≥1:80 in adults for definite diagnosis, ≥1:40 for probable) 3
  • Type 2 AIH: Anti-LKM1 positive (≥1:20 in children, ≥1:80 in adults) 3, 1
  • Diagnostic accuracy improves from 58% to 74% when two autoantibodies are detected 1

• Biochemical markers: Measure serum aminotransferases (AST/ALT), which are characteristically elevated with a predominant aminotransferase pattern 3, 2

  • Calculate ALP:AST ratio—typically <1.5 in AIH (helps distinguish from cholestatic disorders) 2, 4

• Immunoglobulins: Assess serum IgG or total gamma-globulin levels 1, 2

  • Definite AIH: IgG ≥1.5 times normal 3
  • Probable AIH: Any degree of hypergammaglobulinemia 3

Mandatory Exclusions

Rule out competing diagnoses before confirming AIH:

• Viral hepatitis: Negative markers for hepatitis A, B, and C viruses 3
• Genetic liver diseases: Normal alpha-1 antitrypsin phenotype, ceruloplasmin, iron, and ferritin levels 3
• Toxic injury: Alcohol intake <25 g/day for definite diagnosis (<50 g/day for probable); no recent hepatotoxic drug use (particularly minocycline, nitrofurantoin, isoniazid, propylthiouracil, methyldopa) 3

Histological Assessment

Liver biopsy is essential and must be performed unless active contraindications exist 1, 4:

• Interface hepatitis (periportal hepatitis): The histologic hallmark—portal inflammation extending into the hepatic lobule with disruption of the limiting plate 3, 1
• Plasma cell infiltration: Characteristic but not required for diagnosis 3
• Exclusionary findings: No biliary lesions, granulomas, or prominent changes suggesting alternative diagnoses 3

Critical pitfall: Serum aminotransferase and gamma-globulin levels do not predict histologic severity or presence of cirrhosis—biopsy provides essential prognostic information 3

Diagnostic Scoring Systems

Use the simplified criteria for routine clinical practice 3, 1:

Parameter	Points
ANA or SMA ≥1:40 (or anti-LKM1 ≥1:40 or anti-SLA positive)	+1
ANA or SMA ≥1:80	+2
IgG >upper limit of normal	+1
IgG >1.1× upper limit of normal	+2
Liver histology compatible with AIH	+1
Liver histology typical of AIH	+2
Absence of viral hepatitis	+2

• ≥6 points = probable AIH
• ≥7 points = definite AIH 3

For atypical or diagnostically challenging cases, use the comprehensive International Autoimmune Hepatitis Group scoring system (includes gender, ALP:AST ratio, autoantibodies, viral markers, drug history, alcohol intake, histology, concurrent autoimmune diseases, and HLA status) 3:

• Pre-treatment score >15 = definite AIH
• Pre-treatment score 10-15 = probable AIH 3, 2

Important caveat: A single low autoantibody titer should never exclude AIH, nor should high titers alone establish the diagnosis without other supportive findings 1

First-Line Treatment

Treatment Indications

Offer immunosuppressive treatment to the following patients 3, 2:

• Moderate to severe disease (any of the following):

  • Serum AST >5× normal
  • Serum globulins >2× normal
  • Liver biopsy showing confluent necrosis 3

• Additional treatment candidates:

  • Symptomatic patients (regardless of biochemical severity) 3, 2
  • Patients with established cirrhosis on biopsy 3
  • Young patients (to prevent cirrhosis development over decades) 3

Rationale: Untreated moderate to severe AIH progresses to cirrhosis in 82% within 5 years with 45% mortality; bridging or multiacinar necrosis carries 40% mortality within 6 months 3, 2, 4

Standard First-Line Regimen

Initiate combination therapy with prednisone and azathioprine 4, 5, 6:

• Corticosteroids: Essential for remission induction 5, 6
• Azathioprine: Added as steroid-sparing agent with gradual corticosteroid tapering; best for remission maintenance 5, 6

This combination achieves biochemical and histological remission in approximately 80% of patients 4, 6, 7

Treatment Goals

Aim for complete remission defined as 4:

• Normalization of transaminases and IgG levels
• Resolution of symptoms
• Histological improvement with reduction of inflammation

Monitoring Considerations

Asymptomatic patients with mild interface hepatitis (Ishak necroinflammatory score 4-6) and normal or minimally elevated liver tests: Consider monitoring without immediate treatment, with repeat biopsy after 2-3 years if liver tests remain abnormal 3

Common pitfall: Benefits of immunosuppression in asymptomatic older patients with mild disease are not established—individualize based on age, comorbidities, and disease progression risk 3

Second-Line Options

For patients with intolerance or inadequate response to standard therapy (20-40% of patients), consider 8, 5, 9:

• Mycophenolate mofetil
• Tacrolimus
• Cyclosporine
• Sirolimus
• Rituximab (for refractory cases)

Treatment withdrawal is achievable in <20% of patients after 2 years of sustained remission—most require lifelong therapy 5, 7