The article provides a comprehensive guide for clinicians to interpret alterations in liver enzyme levels, which can be challenging even for experienced practitioners. It reviews the functional anatomy and pathophysiology of the liver, classifying enzyme alterations as either hepatocellular or cholestatic. The article emphasizes the importance of understanding normal ranges and reference limits, which can vary among laboratories. It outlines a step-by-step approach to evaluating liver enzyme alterations, considering the patient's geographical location, age, comorbid conditions, and medication history. The article details the clinical significance of different patterns of enzyme alterations, such as marked and moderate increases in aminotransferase levels, which are often associated with acute liver injury, and mild increases, which can be caused by various conditions including chronic viral hepatitis, autoimmune hepatitis, and nonalcoholic fatty liver disease. It also discusses the role of specific tests like liver ultrasound, liver biopsy, and serological tests in diagnosing these conditions. The article concludes by emphasizing the importance of interpreting enzyme alterations within the clinical context and the need for a thorough diagnostic work-up to identify the underlying cause.The article provides a comprehensive guide for clinicians to interpret alterations in liver enzyme levels, which can be challenging even for experienced practitioners. It reviews the functional anatomy and pathophysiology of the liver, classifying enzyme alterations as either hepatocellular or cholestatic. The article emphasizes the importance of understanding normal ranges and reference limits, which can vary among laboratories. It outlines a step-by-step approach to evaluating liver enzyme alterations, considering the patient's geographical location, age, comorbid conditions, and medication history. The article details the clinical significance of different patterns of enzyme alterations, such as marked and moderate increases in aminotransferase levels, which are often associated with acute liver injury, and mild increases, which can be caused by various conditions including chronic viral hepatitis, autoimmune hepatitis, and nonalcoholic fatty liver disease. It also discusses the role of specific tests like liver ultrasound, liver biopsy, and serological tests in diagnosing these conditions. The article concludes by emphasizing the importance of interpreting enzyme alterations within the clinical context and the need for a thorough diagnostic work-up to identify the underlying cause.