What are the diagnostic criteria and treatment options for autoimmune hepatitis?

Diagnostic Criteria and Treatment Options for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis requires a combination of serological, biochemical, and histological findings, along with exclusion of other liver diseases, while treatment should be offered to all patients with moderate to severe disease to improve survival outcomes.

Diagnostic Criteria

Clinical and Laboratory Features

• Autoimmune hepatitis (AIH) is characterized by hypergammaglobulinemia/elevated serum IgG, circulating autoantibodies, and interface hepatitis on liver biopsy 1, 2
• Predominant serum aminotransferase abnormality with globulin, γ-globulin or IgG levels ≥1.5 times normal is characteristic of definite AIH 1
• Female sex is a supportive feature that contributes to diagnostic scoring 1
• The alkaline phosphatase (ALP) to AST (or ALT) ratio is typically <1.5 in AIH 1

Serological Markers

• Conventional autoantibodies include antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and antibodies to liver kidney microsome type 1 (anti-LKM1) 1, 2
• For definite AIH diagnosis, antibody titers should be ≥1:80 in adults and ≥1:20 in children 1
• Additional supportive antibodies include anti-asialoglycoprotein receptor (anti-ASGPR), anti-liver cytosol type 1 (anti-LC1), anti-soluble liver antigen/liver pancreas (anti-SLA/LP), anti-actin, and perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) 1, 2

Histological Features

• Liver biopsy is essential for diagnosis, evaluating disease severity, and determining treatment need 1
• Interface hepatitis is the histological hallmark of AIH, characterized by portal tract expansion by mononuclear infiltrate with disruption of the limiting plate 1
• Portal plasma cell infiltration is typical but not pathognomonic; plasma cells are identified by their eccentric, clock-face nucleus and pale perinuclear cytoplasmic crescent 1, 3
• Hepatocyte rosetting is another supportive histological feature 1

Exclusion Criteria

• All patients must be evaluated for hereditary conditions (Wilson disease, α1-antitrypsin deficiency, genetic hemochromatosis), viral hepatitis (A, B, C), and drug-induced liver injury 1, 2
• Absence of biliary lesions, granulomas, or other changes suggestive of alternative diagnoses is required 1
• Alcohol consumption should be <25 g/day for definite diagnosis and <50 g/day for probable diagnosis 1

Diagnostic Scoring Systems

Original Revised Scoring System

• The comprehensive scoring system developed by the International Autoimmune Hepatitis Group includes parameters such as gender, ALP:AST ratio, serum globulin/IgG levels, autoantibodies, viral markers, drug history, alcohol intake, histology, and other autoimmune diseases 1
• Pre-treatment scores >15 indicate definite AIH, while scores 10-15 suggest probable AIH 1
• Post-treatment scores >17 indicate definite AIH, while scores 12-17 suggest probable AIH 1

Simplified Scoring System

• The simplified system includes four parameters: autoantibodies, IgG levels, liver histology, and absence of viral hepatitis 1
• ≥7 points indicate definite AIH, while ≥6 points suggest probable AIH 1
• This system has approximately 90% sensitivity and specificity but has limitations in patients with acute presentations and atypical cases 4

Special Diagnostic Considerations

Atypical Presentations

• Acute severe (fulminant) AIH may present with centrilobular hemorrhagic necrosis, lymphoplasmatic infiltration, and lymphoid aggregates 1
• Centrilobular (zone 3) necrosis occurs in 29% of AIH patients and can be mistaken for toxic, ischemic, hypoxic, or drug-induced injury 1
• In patients with acute presentations where antibodies may be absent and IgG normal, a short (≤2 weeks) trial of prednisolone may have diagnostic value 1

Diagnostic Challenges

• Distinguishing AIH from drug-induced liver injury can be difficult; clinical and histological features along with resolution after drug withdrawal can help differentiate 1
• Overlap syndromes with primary biliary cholangitis or primary sclerosing cholangitis should be considered when cholestatic features are present 1
• Ethnic variations exist in AIH presentation, with more severe manifestations reported in African Americans and Alaska Natives 2

Treatment Options

Indications for Treatment

• Patients with moderate or severe AIH, young patients, symptomatic patients, and those with cirrhosis should be offered immunosuppressive treatment due to clear survival benefits 1
• Untreated moderate to severe AIH can progress to cirrhosis in 82% of patients within 5 years, with 45% mortality 1
• Treatment may be considered in asymptomatic patients on a trial basis to assess symptom improvement 1

Treatment Monitoring

• Patients should be monitored in a designated liver clinic, ideally with specialist gastroenterology or liver nurse support 1
• Regular monitoring of immunosuppressive therapy should be arranged in either primary or secondary care 1
• Lifelong monitoring is recommended as severe relapse may occur even after apparent spontaneous resolution 1

Special Considerations

• Spontaneous recovery may occur in AIH, making it difficult to justify treating patients with normal serum transaminases, normal globulin/IgG, and minimal necroinflammatory activity on biopsy 1
• Drug-related AIH may resolve upon drug withdrawal, though this is poorly documented as most reported cases receive immunosuppressive treatment 1

Practical Approach to Diagnosis

1. Evaluate clinical presentation and laboratory findings (elevated transaminases, hypergammaglobulinemia) 1
2. Test for conventional autoantibodies (ANA, SMA, anti-LKM1) and additional markers if needed 1, 2
3. Exclude viral hepatitis, drug-induced liver injury, and hereditary liver diseases 1, 2
4. Perform liver biopsy to confirm diagnosis and assess disease severity 1
5. Apply diagnostic scoring systems to classify as definite or probable AIH 1
6. Consider treatment trial with corticosteroids in uncertain cases with acute presentation 1