What are the typical liver function test (LFT) results for a patient with autoimmune hepatitis?

Typical Liver Function Tests in Autoimmune Hepatitis

Autoimmune hepatitis characteristically presents with elevated aminotransferases (AST and ALT), elevated serum IgG or gamma-globulin levels (>1.5× upper limit of normal in most cases), and an alkaline phosphatase to AST ratio <1.5, though approximately 15-39% of patients may have normal IgG levels, particularly in acute presentations. 1, 2

Primary Biochemical Pattern

Aminotransferase Elevation

• AST and ALT are typically elevated 5-20 times the upper limit of normal in most AIH presentations 1
• The pattern is predominantly hepatocellular rather than cholestatic 1
• In acute presentations, AST and ALT may exceed 400 IU/mL 1
• An AST/ALT ratio >1.5 or ALT >5× ULN with positive autoantibodies strongly suggests AIH 2

Alkaline Phosphatase Pattern

• **ALP/AST ratio <1.5 supports AIH diagnosis**, while a ratio >3 argues against it 1, 3
• ALP elevation is typically mild to moderate compared to the aminotransferase elevation 1
• If a cholestatic pattern (elevated ALP) is present, consider AIH-PBC or AIH-PSC overlap syndromes and perform AMA testing and cholangiography 1

Immunoglobulin and Protein Abnormalities

IgG and Gamma-Globulin Elevation

• Approximately 85% of AIH patients have elevated serum IgG or gamma-globulin levels (>1.5× ULN in definite cases) 2, 3
• Hypergammaglobulinemia is polyclonal and represents a central diagnostic element 2
• Selective elevation of IgG without IgA and IgM elevation is particularly suggestive of AIH 2

Important Caveat About Normal Globulins

• 15-39% of AIH patients present with normal IgG/globulin levels, particularly in acute-onset disease 2, 3
• In acute presentations specifically, 25-39% have normal IgG levels 2, 3
• Normal globulin levels do NOT exclude AIH and should not dissuade you from pursuing the diagnosis 2

Bilirubin Patterns

• Serum bilirubin is variable, ranging from normal to >20 mg/dL depending on disease severity 1
• In severe cases meeting Hy's Law criteria (AST/ALT >3× ULN plus bilirubin >2× ULN), there is 9-12% risk of death or need for transplantation 1
• Bilirubin elevation is typically less prominent than aminotransferase elevation in chronic presentations 4

Diagnostic Scoring Integration

Revised Original IAIHG Scoring System

The biochemical parameters contribute to diagnosis as follows 1:

• ALP/AST ratio <1.5: +2 points
• Serum globulin or IgG >2.0× ULN: +3 points
• Serum globulin or IgG 1.5-2.0× ULN: +2 points
• Serum globulin or IgG 1.0-1.5× ULN: +1 point

Simplified Scoring System

• IgG >ULN: +1 point 1
• IgG >1.1× ULN: +2 points 1
• Combined with autoantibodies (≥2 points), histology (≥1 point), and negative viral markers (+2 points), a score ≥7 indicates definite AIH and ≥6 indicates probable AIH 1, 2

Monitoring Disease Activity

Serologic Markers for Follow-up

• Both ALT and IgG are most complementary for assessing disease activity 4
• Normalization of both ALT and IgG identifies patients at low risk of fibrosis progression, though about half may still have residual histologic activity (HAI 4-5) 4
• Presence of both elevated ALT and IgG indicates high inflammatory activity (HAI ≥6) with 99% sensitivity 4
• Elevation of either IgG or ALT is associated with residual inflammatory activity in almost all patients 4

Critical Exclusions Required

Before diagnosing AIH based on LFT patterns, you must exclude 3:

• Viral hepatitis (HBV, HCV, HAV, HEV) - check serologic markers 1
• Drug-induced liver injury - detailed medication history including over-the-counter and herbals 1
• Wilson's disease - especially in younger patients; check ceruloplasmin and 24-hour urinary copper 1, 5
• Alcoholic liver disease - alcohol intake history 1

Common Pitfalls to Avoid

• Do not dismiss AIH because globulins are normal - this will miss 15-39% of cases 2
• Do not assume a cholestatic pattern excludes AIH - consider overlap syndromes 1
• Do not rely solely on LFTs - autoantibodies (ANA, SMA ≥1:80 or anti-LKM1 ≥1:40) and liver histology showing interface hepatitis are essential for diagnosis 1, 5, 3
• In COVID-19 patients with AIH, do not presume LFT deterioration as disease flare without biopsy confirmation 1