What is the possible diagnosis for a patient with a high Absolute Eosinophil Count (AEC), elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) levels with an ALT/AST ratio greater than 1, presenting with symptoms of anorexia and fever?

Differential Diagnosis: High AEC with Elevated Transaminases (ALT>AST), Anorexia, and Fever

The most likely diagnoses to consider are hypereosinophilic syndrome (HES) with gastrointestinal involvement, eosinophilic granulomatosis with polyangiitis (EGPA), drug-induced liver injury with eosinophilia, or parasitic infection causing both eosinophilia and hepatic inflammation.

Primary Diagnostic Considerations

Hypereosinophilic Syndromes (HES)

• HES is characterized by peripheral eosinophilia (AEC >1500 cells/μL) with organ/tissue damage due to eosinophilic infiltration, and up to 38% of patients present with gastrointestinal symptoms including anorexia 1
• When HES affects the gastrointestinal tract including the liver, patients can present with elevated transaminases alongside constitutional symptoms like fever and anorexia 1
• The key distinguishing feature is the marked peripheral eosinophilia (>1500 cells/μL), which is rare in isolated eosinophilic esophagitis but common in systemic eosinophilic disorders 1
• Further screening for upper and lower GI involvement, plus monitoring for other organ involvement (skin, lung, heart, neurologic) consistent with multisystem HES is essential 1

Eosinophilic Granulomatosis with Polyangiitis (EGPA)

• EGPA is a systemic eosinophilic vasculitis that presents with peripheral blood eosinophilia and tissue infiltration, potentially affecting the liver 1
• The clinical presentation typically follows three stages: prodromal (allergic rhinitis, asthma), eosinophilic (peripheral eosinophilia with tissue infiltration), and vasculitic (necrotizing vasculitis with multi-organ dysfunction) 1
• Only 30-40% of patients will have positive ANCA, so negative ANCA does not exclude the diagnosis 1
• Constitutional symptoms including fever and anorexia are common during the eosinophilic and vasculitic phases 1

Drug-Induced Liver Injury with Eosinophilia

• Medication-induced liver injury causes 8-11% of cases with elevated liver enzymes and can present with peripheral eosinophilia in certain drug reactions 2
• The ALT/AST ratio >1 is consistent with hepatocellular injury pattern seen in drug-induced hepatitis 2, 3
• A complete medication review including prescription drugs, over-the-counter products, and herbal supplements is mandatory 2

Alcoholic Hepatitis (Less Likely Given ALT>AST)

• While alcoholic hepatitis presents with fever, anorexia, and elevated transaminases, it characteristically shows AST/ALT ratio >1.5-2.0, typically with AST >50 IU/mL but rarely above 300 IU/mL 1
• The pattern described (ALT>AST) makes alcoholic hepatitis less likely, though early stages or concurrent conditions could alter this ratio 1, 4
• Neutrophilia rather than eosinophilia is the typical finding in alcoholic hepatitis 1

Critical Diagnostic Algorithm

Immediate Laboratory Evaluation

• Complete liver panel including AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, and PT/INR to assess synthetic function and cholestatic patterns 2
• Confirm absolute eosinophil count >1500 cells/μL to meet HES criteria 1
• Viral hepatitis serologies (HBsAg, anti-HBc IgM, anti-HCV) to exclude viral causes 2
• Creatine kinase to exclude muscle injury as source of transaminase elevation 2, 5

Specialized Testing for Eosinophilic Disorders

• ANCA testing (though only 30-40% positive in EGPA) 1
• Serum IgE levels (often markedly elevated in EGPA) 1
• Stool examination for ova and parasites (three samples) to exclude parasitic causes of eosinophilia
• Troponin and ECG if cardiac involvement suspected (eosinophilic myocarditis can occur in HES) 1

Imaging Studies

• Abdominal ultrasound as first-line imaging with 84.8% sensitivity and 93.6% specificity for detecting hepatic abnormalities 2
• Chest X-ray or CT to evaluate for pulmonary infiltrates characteristic of EGPA 1

Tissue Diagnosis

• Upper and lower endoscopy with biopsies if gastrointestinal HES suspected, looking for eosinophilic infiltration 1
• Liver biopsy (via transjugular route if coagulopathy present) may be needed if diagnosis remains unclear, particularly to distinguish between eosinophilic infiltration versus other causes 1

Important Clinical Pitfalls

Do Not Assume NAFLD or Viral Hepatitis Alone

• While NAFLD typically presents with ALT>AST ratio, it does not explain the marked eosinophilia 2
• The combination of high AEC with elevated transaminases requires investigation beyond common liver diseases 1

Recognize the Urgency of Systemic Eosinophilic Disorders

• HES and EGPA can cause life-threatening cardiac, neurologic, and pulmonary complications requiring urgent specialist consultation 1
• Eosinophilic myocarditis can present acutely and is a medical emergency 1

Consider Geographic and Exposure History

• Parasitic infections (strongyloidiasis, toxocariasis, schistosomiasis) can cause both eosinophilia and hepatic inflammation
• Travel history and exposure to contaminated water/soil is essential

Recommended Specialist Referrals

• Immediate consultation with allergy/immunology or rheumatology for suspected HES or EGPA 1
• Hepatology referral if liver enzymes remain elevated >6 months or if synthetic dysfunction develops 2
• Gastroenterology for endoscopic evaluation if gastrointestinal eosinophilic disease suspected 1