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Fluctuating transaminitis (elevated AST/ALT) following prolonged jaundice requires a careful and structured diagnostic approach. Here's a framework for investigations, with a differential diagnosis tailored to this clinical context:
⚠️ Clinical Context Summary
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Prolonged jaundice: Suggests either hepatocellular, cholestatic, or hemolytic causes.
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Fluctuating transaminitis: Indicates intermittent or ongoing hepatocellular injury.
🧪 Stepwise Investigation Plan
1. Initial Blood Tests
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Liver Function Tests (LFTs): Total/Direct bilirubin, AST, ALT, ALP, GGT, Albumin, INR.
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Full Blood Count (FBC): Look for anemia, thrombocytopenia.
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Renal function and electrolytes
2. Viral Hepatitis Screen
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HAV IgM
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HBsAg, Anti-HBc IgM, HBeAg, Anti-HBs
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HCV antibody and HCV RNA
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HEV IgM and HEV RNA (especially in endemic areas)
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EBV/CMV serology, especially in younger patients
3. Autoimmune Panel
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ANA, ASMA, LKM-1, AMA
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IgG levels: Elevated in autoimmune hepatitis
4. Metabolic & Genetic Workup
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Serum ceruloplasmin and 24h urinary copper: Wilson’s disease
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Ferritin, Transferrin saturation: Hemochromatosis
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Alpha-1 antitrypsin levels
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Thyroid function tests: Hypothyroidism can cause liver enzyme abnormalities
5. Drug and Toxin Exposure
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Comprehensive drug history: Including herbal/supplements, acetaminophen, statins, antiepileptics
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Alcohol use history
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Consider toxicology screening if suspicious
6. Imaging Studies
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Abdominal Ultrasound (US): Biliary obstruction, fatty liver, liver size
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MRCP: If cholestatic pattern or suspicion of sclerosing cholangitis
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Elastography/Fibroscan: Evaluate liver fibrosis
7. Liver Biopsy (if needed)
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If diagnosis remains unclear or to stage chronic liver disease
🧠 Differential Diagnoses to Consider
| Category | Examples |
|---|---|
| Viral | Chronic Hep B/C, EBV, CMV, HEV |
| Autoimmune | Autoimmune hepatitis, overlap syndromes |
| Toxic/Drug-induced | Intermittent exposure to hepatotoxic drugs, alcohol |
| Genetic/Metabolic | Wilson’s disease, hemochromatosis, A1AT deficiency |
| Obstructive/Biliary | Primary sclerosing cholangitis (PSC), Primary biliary cholangitis (PBC), post-cholecystectomy syndrome |
| Ischemic/Hypoxic injury | Shock liver, congestive hepatopathy |
| Relapsing infections | Leptospirosis, malaria, dengue (depending on geography) |
🔁 Why Transaminases Fluctuate
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Intermittent hepatocyte injury (e.g., viral flares, autoimmune activity)
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Cholestatic episodes with secondary hepatocellular involvement
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Subclinical re-exposures to triggers (e.g., drugs or alcohol)
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Partial recovery with relapses
Would you like a decision tree or summary table for different types of liver injury patterns (hepatocellular vs cholestatic vs mixed)?
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