Interpret the laboratory results of a 53‑year‑old woman with mild neutrophilia, eosinophilia, normal renal function, elevated AST (60 U/L), ALT (112 U/L), ALP (309 U/L), GGT (257 U/L), and ferritin 147 µg/L.

Laboratory Interpretation: 53-Year-Old Woman with Hepatobiliary Enzyme Elevation and Eosinophilia

This bloodwork reveals a cholestatic pattern of liver injury with markedly elevated alkaline phosphatase (309 U/L) and GGT (257 U/L), accompanied by mild transaminase elevation (AST 60 U/L, ALT 112 U/L), mild eosinophilia (1.00 × 10e9/L), and borderline elevated ferritin (147 µg/L), which together strongly suggest an autoimmune cholestatic liver disease—most likely primary biliary cholangitis (PBC)—requiring immediate serological testing for anti-mitochondrial antibodies (AMA) and anti-nuclear antibodies (ANA). 1

Hepatobiliary Pattern Analysis

Cholestatic Predominance

• The disproportionate elevation of ALP (309 U/L, >2.8× upper limit) and GGT (257 U/L, >7× upper limit) compared to transaminases defines a cholestatic injury pattern. 2 The GGT:ALP ratio is markedly elevated, which is characteristic of autoimmune cholestatic diseases. 1

• In early-stage PBC, 29.2% of patients have normal ALP levels, but GGT elevation is more robust—with 29.2% showing GGT >10× upper limit of normal even when ALP is only mildly elevated. 1 This patient's pattern fits this profile precisely.

• The ALT:AST ratio of approximately 1.9:1 argues against advanced fibrosis or cirrhosis, where the ratio typically inverts to <1. 2 This suggests early-stage disease.

Critical Next Steps for Liver Disease Evaluation

Order the following autoimmune liver disease panel immediately: 2

• Anti-mitochondrial antibody (AMA) and AMA-M2: Detection rate of 66.7% and 45.8% respectively in early-stage PBC 1
• Anti-nuclear antibody (ANA): When AMA/AMA-M2 are negative, ANA positivity reaches 92.3% in early PBC, with ANA centromere pattern being most common (38.5%) 1
• Anti-smooth muscle antibody and serum immunoglobulins: To evaluate for autoimmune hepatitis overlap 2
• Anti-LKM antibody: For type 2 autoimmune hepatitis 2

Hematologic Findings

Eosinophilia Interpretation

• The absolute eosinophil count of 1.00 × 10e9/L (reference 0.00-0.30) represents significant eosinophilia that requires investigation. 2 In the context of liver disease, this raises three primary considerations:

1. Drug-induced liver injury with hypersensitivity: Review all medications, particularly antibiotics, NSAIDs, and herbal supplements
2. Parasitic infection: Consider strongyloidiasis, toxocariasis, or other helminthic infections, especially with travel history
3. Autoimmune hepatitis: Eosinophilia can accompany autoimmune liver disease 3

Mild Neutrophilia

• The neutrophil count of 6.10 × 10e9/L (reference 2.00-6.00) represents borderline elevation. 4 Women typically have neutrophil counts 0.66 × 10e9/L higher than men, and afternoon sampling can add another 0.50 × 10e9/L. 4 This mild elevation is likely physiologic or reactive to inflammation rather than pathologic.

Normal Complete Blood Count

• The hemoglobin (148 g/L), hematocrit (0.450 L/L), and RBC indices are all normal, excluding anemia as a contributor to the clinical picture. 2

Iron Studies Interpretation

Borderline Elevated Ferritin with Normal Iron Parameters

The ferritin of 147 µg/L (reference 20-120) is mildly elevated, but iron saturation (37%) and TIBC (60 µmol/L) are both normal, indicating this is NOT iron overload. 5, 6

• Ferritin is an acute-phase reactant that rises with inflammation, infection, and liver disease. 2, 6 In the context of elevated liver enzymes and possible autoimmune disease, this ferritin elevation reflects inflammation rather than iron excess.

• The normal transferrin saturation (37%, reference 14-51%) definitively excludes hemochromatosis or significant iron overload. 3 In true iron overload, transferrin saturation typically exceeds 45-50%. 5

• This pattern (mildly elevated ferritin with normal iron saturation) is characteristic of inflammatory liver disease, not iron storage disease. 3 Autoimmune hepatitis can present with elevated ferritin and transferrin saturation that mimics iron overload, but liver biopsy distinguishes these entities. 3

Differential Diagnosis Priority

Primary Biliary Cholangitis (Most Likely)

The combination of marked GGT elevation (>7× ULN), disproportionate to ALP elevation, in a 53-year-old woman strongly suggests early-stage PBC. 1 The absence of jaundice (normal bilirubin implied by chemistry panel) and normal albumin indicate early disease before cirrhosis develops. 1

Adult-Onset Still's Disease (Less Likely but Consider)

• While ferritin is elevated, it is not in the extreme range (>5000 ng/mL) typical of AOSD. 2, 7 AOSD with hemophagocytic syndrome shows mean ferritin of 18,179 ng/mL. 7
• The absence of fever, rash, and arthritis documented in the clinical context makes AOSD unlikely. 2
• Eosinophilia is not a typical feature of AOSD, which more commonly shows neutrophilia. 2

Drug-Induced Liver Injury

• The eosinophilia raises concern for drug-induced hypersensitivity hepatitis. 3 Obtain detailed medication history including over-the-counter drugs and supplements.

Recommended Diagnostic Algorithm

Immediate Laboratory Testing

1. Autoimmune liver panel: AMA, AMA-M2, ANA (with reflex to specific patterns including centromere), anti-smooth muscle antibody, serum IgM and IgG 2, 1
2. Viral hepatitis serologies: Hepatitis B surface antigen, hepatitis C antibody with reflex PCR 2
3. Stool ova and parasites (×3 specimens): To evaluate eosinophilia 2
4. Comprehensive metabolic panel: If not already complete, to assess bilirubin and albumin 2

Imaging

• Abdominal ultrasound: To evaluate for biliary obstruction, hepatomegaly, and exclude structural causes of cholestasis 2

Follow-Up Based on Results

• If AMA/AMA-M2 positive: Diagnosis of PBC is confirmed; proceed to liver biopsy for staging 1
• If AMA/AMA-M2 negative but ANA positive (especially centromere pattern): PBC remains likely; liver biopsy is diagnostic 1
• If all autoimmune markers negative: Consider liver biopsy to evaluate for drug-induced injury, eosinophilic infiltration, or other causes 3

Clinical Pitfalls to Avoid

• Do not attribute the elevated ferritin to iron overload when transferrin saturation is normal. 3 This is a common error that delays diagnosis of the underlying inflammatory liver disease.

• Do not dismiss PBC when ALP is only moderately elevated if GGT is markedly elevated. 1 Early PBC shows disproportionate GGT elevation.

• Do not overlook ANA testing when AMA is negative. 1 ANA-positive, AMA-negative PBC accounts for a significant minority of cases and has similar prognosis.

• Do not ignore the eosinophilia. 2 While it may be reactive to liver disease, parasitic infection and drug hypersensitivity must be excluded.