Acute Viral Hepatitis: This is often the first consideration for markedly elevated liver enzymes, as viral hepatitis (such as hepatitis A, B, or C) can cause a significant increase in liver enzymes due to the liver's inflammatory response to the virus.

Acetaminophen Overdose: A common cause of acute liver failure, acetaminophen toxicity can lead to extremely high liver enzymes. It's a critical diagnosis to consider due to the availability of specific antidotes like N-acetylcysteine.
Ischemic Hepatitis (Shock Liver): This condition occurs when there's a significant reduction in blood flow to the liver, often seen in shock or severe hypotension. It can cause a dramatic elevation in liver enzymes.
Autoimmune Hepatitis: Although less common, autoimmune hepatitis can present with very high liver enzymes due to the immune system's attack on liver cells.

Budd-Chiari Syndrome: A rare condition caused by thrombosis of the hepatic veins, which can lead to acute liver failure. It's crucial to diagnose early as it may require urgent intervention.
Wilson's Disease: A genetic disorder leading to copper accumulation in the liver, which can cause acute liver failure. Early diagnosis is vital for treatment and potential liver transplantation.
Malignant Infiltration: Metastatic disease or primary liver malignancies can cause significant elevations in liver enzymes, especially if there's extensive liver involvement.

Toxicity from Other Medications or Toxins: Certain medications (other than acetaminophen) and toxins can cause severe liver injury, leading to high liver enzymes. Examples include certain antibiotics, anticonvulsants, and herbal supplements.
Reye's Syndrome: A rare but serious condition that causes swelling in the liver and brain, often associated with the use of aspirin during viral infections.
Vascular Malformations or Thrombosis: Rare vascular conditions affecting the liver can lead to ischemia or infarction, resulting in elevated liver enzymes.