Are all elevated liver function tests (LFTs) indicative of acute liver injury?

From the Guidelines

Not all high liver function tests indicate acute liver injury. Elevated liver function tests (LFTs) can result from various conditions beyond acute liver injury, including chronic liver diseases, medication effects, alcohol use, viral infections, autoimmune disorders, and even non-liver related issues 1. For instance, isolated elevations in alkaline phosphatase (ALP) might indicate biliary obstruction rather than liver cell damage, as ALP levels can be increased in cholestatic liver disease 1. Similarly, mild elevations in transaminases (ALT and AST) can occur with strenuous exercise, certain medications like statins, or fatty liver disease without representing acute injury.

When evaluating abnormal LFTs, it's essential to consider the pattern of elevation, the magnitude of increase, and the clinical context 1. The severity of abnormal aminotransferase can be classified as mild, moderate, or severe, with moderate and severe being discussed collectively due to significant clinical overlap 1. Acute liver injury typically presents with marked elevations in transaminases (often >10-20 times normal), while more modest elevations might represent chronic conditions or transient changes. A thorough history, physical examination, and sometimes additional testing are necessary to determine the underlying cause of elevated liver enzymes and distinguish between acute injury and other conditions.

Key points to consider in the evaluation of abnormal LFTs include:

• The specificity of ALT elevations for liver injury, as ALT is concentrated primarily in the liver 1
• The potential for AST elevations to be caused by disorders involving the heart, skeletal muscle, kidneys, brain, and red blood cells 1
• The importance of considering the clinical context and pattern of LFT abnormalities to determine the underlying cause 1
• The need for a thorough history, physical examination, and sometimes additional testing to distinguish between acute liver injury and other conditions 1

From the Research

Definition of Acute Liver Injury

Acute liver injury refers to a sudden and severe damage to the liver, which can be caused by various factors such as viruses, toxins, or medications.

Relationship Between High Liver Function Test and Acute Liver Injury

• Not all high liver function tests indicate acute liver injury, as elevated liver function tests can be found in 25% of patients presenting with unspecific symptoms or during a routine health checkup 2.
• Liver disease can present without abnormal liver function tests, and conversely, abnormal liver function tests do not always indicate liver disease 3, 4.
• The pattern of liver injury can be either hepatocellular or cholestatic, and a combination of a careful history and clinical examination along with interpretation of pattern of liver test abnormalities can often identify type and aetiology of liver disease 3.

Causes of Elevated Liver Function Tests

• Elevated liver function tests can be caused by various factors, including non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), viral hepatitis, and statin use 2, 5.
• Statins can cause dose-dependent borderline elevations of liver function tests over time, but these elevations are clinically and statistically insignificant 5.

Diagnostic Approach

• A detailed medical history and a thorough clinical examination should be performed first to narrow down possible causes of elevated liver function tests 2.
• Laboratory diagnostics and obligatory ultrasound scan can be supplemented by non-invasive methods (e.g. elastography, MRI/MRCP/CT) and in selected cases invasive methods (liver biopsy, ERCP) 2.
• The severity of liver injury is best assessed by composite scores like the Model for End Stage Liver Disease rather than any single parameter 3.