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

Diagnostic Criteria and Treatment Options for Autoimmune Hepatitis

The diagnosis of autoimmune hepatitis (AIH) requires a combination of serological, biochemical, and histological findings, along with exclusion of other liver diseases, with treatment being essential for patients with moderate to severe disease to improve survival outcomes. 1

Diagnostic Criteria

Clinical and Laboratory Features

• AIH is characterized by hypergammaglobulinemia/elevated serum IgG (present in approximately 85% of patients), circulating autoantibodies, and a predominantly hepatitic pattern with bilirubin and aminotransferases ranging from just above normal to >50 times normal 2, 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, 3
• Elevated liver function tests and beta globulin are characteristic features reflecting hypergammaglobulinemia 3

Autoantibody Testing

• Initial evaluation should include testing for:
  • Antinuclear antibodies (ANA) 4, 3
  • Smooth muscle antibodies (SMA) 4, 3
  • Anti-liver kidney microsomal type 1 antibodies (anti-LKM1) 2, 4
  • Anti-soluble liver antigen (anti-SLA/LP) 4, 3
• Autoantibody patterns help classify AIH into:
  • Type 1: ANA and/or SMA positive (more common in adults) 4
  • Type 2: Anti-LKM1 and/or anti-LC1 positive (more common in children) 4

Histological Features

• Liver biopsy is essential for diagnosis and evaluation of disease severity 2, 4, 3
• Typical histological features include:
  • Interface hepatitis with portal lymphocytic/lymphoplasmacytic infiltrates extending into the lobule 2, 5
  • Emperipolesis (active penetration by one cell into and through a larger cell) 2, 5
  • Hepatic rosette formation 2, 5
• Centrilobular injury with prominent hepatocellular necrosis may represent an early stage of the disease 5

Diagnostic Scoring Systems

International Autoimmune Hepatitis Group (IAIHG) Scoring Systems

• Comprehensive scoring system (1999) includes:
  • 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, 6

Simplified Scoring System (2008)

• Includes four parameters:
  • Autoantibodies (ANA, SMA, LKM, or SLA/LP) 2, 6
  • IgG or γ-globulin levels 2
  • Liver histology (compatible or typical) 2
  • Absence of viral hepatitis 2
• Scoring: ≥7 points indicates definite AIH; 6 points indicates probable AIH 2, 6
• Limitations include lower sensitivity in acute presentations and atypical cases 6, 7

Differential Diagnosis

• Must exclude:
  • Viral hepatitis (hepatitis A, B, C) 2, 4
  • Drug-induced liver injury 2, 4
  • Wilson's disease (check ceruloplasmin) 2, 4
  • Alcoholic liver disease (alcohol consumption <25 g/day for definite AIH) 2
  • Non-alcoholic steatohepatitis 4
  • Primary biliary cholangitis (check for antimitochondrial antibodies) 2, 3
  • Primary sclerosing cholangitis 3

Treatment Options

Standard Therapy

• Treatment is indicated for:
  • Patients with moderate to severe AIH 1, 3
  • Young patients 1
  • Symptomatic patients 1
  • Patients with cirrhosis 1, 3
• Standard induction therapy:
  • Prednisone 15-20 mg/day and azathioprine 1-2 mg/kg/day 3, 8
• Treatment goals:
  • Normalization of transaminases and IgG levels 3
  • Resolution of symptoms 3
  • Histological improvement with reduction of inflammation 3

Alternative Therapies for Non-responders

• Second-line agents include:
  • Budesonide (especially in non-cirrhotic patients) 8
  • Mycophenolate mofetil 8
  • Calcineurin inhibitors (cyclosporine, tacrolimus) 8
  • 6-mercaptopurine or 6-thioguanine 8
  • Rituximab 8
  • Ursodeoxycholic acid (particularly in overlap syndromes) 8

Prognosis and Monitoring

• Untreated moderate to severe AIH can progress to cirrhosis in 82% of patients within 5 years, with 45% mortality 1, 3
• With treatment, approximately 80% of patients achieve remission 3
• Regular monitoring should include:
  • Liver function tests 3
  • IgG levels 3
  • Screening for hepatocellular carcinoma in cirrhotic patients 3
  • Surveillance for esophageal varices in cirrhotic patients 3
• Patients on immunosuppressants should receive counseling for UV-protective measures and dermatological monitoring for non-melanoma skin cancer 2

Special Considerations

• Acute presentation occurs in approximately 25% of cases, sometimes with normal IgG and negative autoantibodies initially 3, 7
• Seronegative AIH can occur with clinical and histological features of AIH without classic autoantibodies 3
• Overlap syndromes with primary biliary cholangitis or primary sclerosing cholangitis should be considered if cholestatic features are present 3
• In diagnostically challenging cases, a trial of steroid therapy with quick tapering may confirm the diagnosis if the disease responds well but recurs after tapering 6