Do patients with acute liver failure always present with elevated liver enzymes, specifically alanine transaminase (ALT) and aspartate transaminase (AST)?

From the Guidelines

No, acute liver failure patients do not always present with elevated liver enzymes. While elevated liver enzymes (such as AST and ALT) are common in acute liver failure, some patients may have normal or only mildly elevated enzyme levels, particularly in late-stage disease or in certain etiologies, as noted in studies 1. This occurs because as massive hepatocyte death progresses, there may be insufficient remaining functional liver cells to release enzymes into the bloodstream. Key points to consider in the diagnosis of acute liver failure include:

• Clinicians should be aware that normal liver enzymes do not exclude acute liver failure, especially in patients with other hallmark features such as coagulopathy (INR ≥1.5) and encephalopathy 1.
• In cases of certain etiologies, enzymes may be dramatically elevated initially but can normalize as the condition worsens.
• Other laboratory findings like hyperbilirubinemia, low albumin, hypoglycemia, and elevated ammonia levels may be more reliable indicators of severe liver dysfunction. The diagnosis of acute liver failure should be based on the complete clinical picture rather than enzyme levels alone, as emphasized in the most recent and highest quality study 1.

From the Research

Presentation of Acute Liver Failure

• Acute liver failure (ALF) is a severe and potentially reversible form of liver insufficiency, characterized by the occurrence of hepatic coagulopathy and hepatic encephalopathy in patients with no previous hepatic disease 2.
• The condition is often preceded by severe acute liver injury (ALI) with an increase in transaminases, jaundice, and deterioration in general condition over a period of hours to weeks 2.
• Patients with ALF usually present at the stage of acute liver damage, with initial diagnostics including a detailed medical history, clinical examination, laboratory diagnostics, and abdominal sonography 2.

Elevated Liver Enzymes in Acute Liver Failure

• A rapid-onset elevation of aminotransferases is a consistent pattern in ALF, indicating hepatocyte injury 3.
• However, the presence of elevated liver enzymes is not a universal feature of ALF, and some patients may not exhibit significant elevations in liver enzymes despite having severe liver injury 4.
• The diagnosis of ALF requires careful review of medications taken, serological testing for possible viral exposure, and consideration of other potential causes of liver injury 3.

Variability in Presentation

• The presentation of ALF can vary depending on the underlying cause, with some patients exhibiting more severe symptoms and others having a more gradual onset of disease 5.
• Complications of liver failure can include encephalopathy, cerebral edema, sepsis, renal failure, gastrointestinal bleeding, and respiratory failure, which can affect the clinical presentation and outcome of ALF 5.
• Despite advances in critical care medicine and emergent liver transplant, mortality rates for ALF remain high, highlighting the importance of early recognition and treatment of the condition 2, 3.