Differential Diagnosis of Elevated Liver Function Tests (LFTs)

Elevated LFTs can be caused by a wide range of conditions affecting the liver. The differential diagnosis can be categorized as follows:

• Single Most Likely Diagnosis

  • Non-alcoholic fatty liver disease (NAFLD): This is the most common cause of elevated LFTs in many populations, particularly in those with risk factors such as obesity, diabetes, and metabolic syndrome. NAFLD can range from simple steatosis to non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis.

• Other Likely Diagnoses

  • Alcoholic liver disease: Liver damage caused by excessive alcohol consumption, which can lead to steatosis, alcoholic hepatitis, and eventually cirrhosis.
  • Viral hepatitis (B and C): Chronic infections with hepatitis B virus (HBV) or hepatitis C virus (HCV) can cause liver inflammation, leading to elevated LFTs and potentially progressing to cirrhosis or liver cancer.
  • Drug-induced liver injury: Many medications and herbal supplements can cause liver damage, leading to elevated LFTs. The pattern of enzyme elevation can sometimes suggest the culprit.
  • Autoimmune hepatitis: A condition where the body's immune system attacks liver cells, leading to inflammation and elevated LFTs.

• Do Not Miss Diagnoses

  • Acetaminophen overdose: A leading cause of acute liver failure, which can present with markedly elevated LFTs. Early recognition and treatment are crucial.
  • Wilson's disease: A genetic disorder leading to copper accumulation in the liver, which can cause liver damage and neurological symptoms. It's essential to diagnose early to prevent long-term damage.
  • Budd-Chiari syndrome: Thrombosis of the hepatic veins, which can cause acute liver failure. It's a rare condition but has a high mortality rate if not promptly treated.
  • Hemochromatosis: A genetic disorder causing excessive iron absorption, leading to iron overload and potential liver damage.

• Rare Diagnoses

  • Alpha-1 antitrypsin deficiency: A genetic disorder that can cause liver disease and lung disease due to the accumulation of abnormal alpha-1 antitrypsin protein.
  • Primary biliary cholangitis (PBC): An autoimmune disease causing progressive destruction of the bile ducts within the liver, leading to cholestasis and elevated LFTs.
  • Primary sclerosing cholangitis (PSC): A chronic liver disease characterized by inflammation and scarring of the bile ducts, often associated with inflammatory bowel disease.
  • Liver metastases: Spread of cancer from other parts of the body to the liver, which can cause elevated LFTs, particularly alkaline phosphatase.

Each of these conditions has a different approach to diagnosis and management, emphasizing the importance of a thorough diagnostic workup for elevated LFTs.