What is the diagnosis and treatment for an adult patient with elevated liver enzymes, positive anti-smooth muscle antibodies, and normal IgG levels?

Diagnosis: Probable Autoimmune Hepatitis

This patient most likely has autoimmune hepatitis (AIH) and should undergo liver biopsy for confirmation followed by prompt initiation of immunosuppressive therapy with prednisone and azathioprine if histology confirms interface hepatitis. 1, 2

Diagnostic Assessment

Current Laboratory Profile Analysis

• Anti-smooth muscle antibody (SMA) titer of 1:160 is highly significant and meets criteria for definite AIH in the simplified scoring system (≥1:80 = 2 points) 1
• AST 100 and ALT 180 demonstrate a predominantly hepatitic pattern with AST/ALT elevation characteristic of AIH 2, 3
• Normal IgG is atypical but does NOT exclude AIH - approximately 15-25% of AIH patients present with normal IgG levels, particularly in acute presentations 1, 2
• The ALP/AST ratio appears favorable for AIH (if ALP is normal or mildly elevated, ratio would be <1.5, scoring +2 points on revised diagnostic system) 1, 3

Applying Simplified Diagnostic Scoring System

Using the International Autoimmune Hepatitis Group simplified criteria 1:

• SMA ≥1:80: +2 points 1
• IgG normal (not >ULN): 0 points 1
• Viral markers (need to confirm negative): +2 points if negative 1
• Liver histology: +1 or +2 points pending biopsy 1

Current score: 2-4 points (probable AIH ≥6, definite AIH ≥7) - this patient needs additional workup to reach diagnostic threshold 1

Critical Next Steps Before Treatment

Essential Exclusions Required Immediately

• Exclude viral hepatitis: Test HBsAg, anti-HBc, anti-HCV with reflex HCV RNA, anti-HAV IgM, and anti-HEV 2, 3
• Exclude drug-induced liver injury (DILI): Obtain detailed medication history including over-the-counter drugs, herbals, and supplements - 9% of suspected AIH cases are actually DILI 3
• Exclude Wilson disease if patient is under age 40: Check ceruloplasmin and 24-hour urinary copper 2
• Exclude alcohol-related liver disease: Quantify daily alcohol intake (<25 g/day supports AIH) 1

Complete Autoantibody Panel

• Test antinuclear antibody (ANA) - present in 80-83% of AIH patients, often coexists with SMA 1, 2
• Consider anti-LKM1, anti-LC1, and anti-SLA/LP if diagnosis remains uncertain, as 20% of AIH patients are seronegative for standard antibodies 2, 3
• Test anti-mitochondrial antibody (AMA) to exclude primary biliary cholangitis overlap syndrome 1

Measure Serum Immunoglobulins Precisely

• Obtain quantitative IgG level - even "normal" IgG in the upper normal range may be relatively elevated for that individual patient 1, 3
• Check serum albumin and globulin separately to calculate A/G ratio - hypergammaglobulinemia is present in 85% of AIH cases 1, 3
• Measure IgA and IgM - selective IgG elevation without IgA/IgM elevation is particularly suggestive of AIH 3

Liver Biopsy is Essential

• Perform liver biopsy before initiating immunosuppression unless acute liver failure requires immediate treatment 2, 3
• Look for interface hepatitis with lymphoplasmacytic infiltration - the hallmark histologic finding 1, 2
• Assess for plasma cell infiltration, hepatocyte rosettes, and emperipolesis - typical but not required features 1, 2
• Exclude biliary changes, ductopenia, or destructive cholangitis that would suggest overlap syndromes 1

Evaluation for Overlap Syndromes

When to Consider AIH-PSC or AIH-PBC Overlap

• If ALP is disproportionately elevated (ALP/AST ratio >1.5), perform cholangiography (MRCP) and test AMA 1
• AIH-PSC overlap occurs in approximately 5-10% of AIH cases and requires both immunosuppression and monitoring for cholangiocarcinoma 1, 4
• Overlap syndromes typically show marked response to corticosteroids but may relapse during dose reduction 4

Treatment Approach Once Diagnosis Confirmed

Standard Induction Therapy

• Initiate prednisone 15-20 mg/day plus azathioprine 1-2 mg/kg/day once AIH is confirmed by biopsy 2, 5
• Treatment should be started promptly to prevent progression - untreated AIH progresses to cirrhosis in 82% within 5 years with 45% mortality 5
• Approximately 80% of patients achieve remission with standard therapy 2, 5

Monitoring Treatment Response

• Check liver enzymes every 2-4 weeks initially to establish treatment response 3
• Treatment goal is complete normalization of both transaminases AND IgG levels 2, 5
• Monitor for azathioprine toxicity with complete blood count and liver function tests 2

Common Diagnostic Pitfalls to Avoid

• Do not exclude AIH based solely on normal IgG - 25-39% of acute presentations have normal or weakly elevated IgG 2, 3
• Do not assume seronegative status rules out AIH - 20% of AIH patients lack standard autoantibodies 2, 3
• Do not start immunosuppression without excluding viral hepatitis and DILI - treating these conditions with corticosteroids worsens outcomes 3
• Do not delay biopsy - histology is essential for diagnosis and provides prognostic information about fibrosis stage 2, 3

Prognosis Considerations

• If cirrhosis is present at diagnosis (25% of cases), initiate hepatocellular carcinoma surveillance and variceal screening 2, 5
• With appropriate treatment, long-term survival approaches that of the general population 2
• Regular monitoring for disease activity is essential as relapse occurs in many patients during treatment reduction 5, 4