Differential Diagnosis

The patient presents with a complex set of symptoms including knee pain, leg and back pain, jaundice, and encephalopathy, with significantly elevated liver enzymes (ALT and AST in 1000) and a high total bilirubin level (TSB high 30), but normal alkaline phosphatase (ALP) and renal function tests (RFT). Given the negative virology, autoimmune screen, and normal abdominal ultrasound, the differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • Acute Liver Failure of Unknown Etiology: Given the rapid progression to jaundice and encephalopathy with extremely high liver enzymes, this diagnosis is highly plausible. The absence of a clear viral or autoimmune cause, along with normal imaging, points towards a potential toxic, metabolic, or idiopathic cause.

• Other Likely Diagnoses

  • Drug-Induced Liver Injury (DILI): This is a common cause of acute liver failure, especially in the absence of viral or autoimmune markers. The patient's history of medication use, including over-the-counter drugs or supplements, should be thoroughly investigated.
  • Wilson's Disease: Although less common, Wilson's disease can present with acute liver failure, especially in young individuals. The normal ALP and presence of neurological symptoms (encephalopathy) could support this diagnosis, but it would typically be associated with low ceruloplasmin levels and Kayser-Fleischer rings.
  • Autoimmune Hepatitis (AIH) with Negative Autoantibodies: While the autoimmune screen is negative, a small percentage of AIH patients may not have detectable autoantibodies at presentation. The diagnosis would require a liver biopsy for confirmation.

• Do Not Miss Diagnoses

  • Budd-Chiari Syndrome: Although the ultrasound is normal, this condition (hepatic vein thrombosis) can cause acute liver failure and should be considered, especially if there's a suspicion of thrombophilia or a history suggestive of thrombotic events.
  • Vascular Causes (e.g., Shock Liver): Any condition leading to significant hypoperfusion of the liver can result in ischemic hepatitis, presenting with markedly elevated liver enzymes. This would be more likely in the context of systemic illness or shock.
  • Toxic Exposures: Certain toxins, including mushrooms (e.g., Amanita phalloides), can cause fulminant liver failure. A detailed history of potential exposures is crucial.

• Rare Diagnoses

  • Reye's Syndrome: A rare condition associated with the use of aspirin during viral infections, leading to acute liver failure and encephalopathy. It's more common in children but can occur in young adults.
  • Mitochondrial Disorders: Certain mitochondrial diseases can present with liver dysfunction among other systemic symptoms. These are rare and would typically have other associated findings or a family history.
  • Lymphoma or Other Malignancies: Although rare, certain malignancies can cause liver failure through infiltration or obstruction. This diagnosis would be considered if other causes are ruled out and there are suggestive findings on imaging or biopsy.