Liver enzyme alterations are a common clinical challenge, often indicating liver damage or bile flow disturbances. This review provides a guide for clinicians to interpret liver enzyme levels, focusing on hepatocellular and cholestatic patterns. The liver's functional anatomy and pathophysiology are briefly reviewed, with a schematic approach to classify enzyme alterations. The review discusses the most common causes of enzyme changes and initial investigations. Liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are primarily found in the liver, with AST also present in the heart, muscles, and kidneys. ALT is more specific to liver damage. Hepatocellular injury leads to elevated AST and ALT levels, while cholestatic injury affects bile flow, increasing alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). The severity of enzyme elevation is classified as mild, moderate, or marked, with marked elevations typically indicating acute liver injury. Acute viral hepatitis, ischemic injury, and toxic liver damage present with distinct patterns. For example, in acute viral hepatitis, AST and ALT levels peak before jaundice appears, while in ischemic injury, AST peaks before ALT. The AST/ALT ratio is useful in diagnosing liver disease, with a ratio >1 suggesting chronic liver disease. In alcoholic liver disease, the AST/ALT ratio is often >1, and pyridoxal-5'-phosphate deficiency may affect ALT levels. Cholestatic injury is characterized by elevated ALP and GGT, often with normal or slightly elevated AST. Conditions like primary biliary cirrhosis and primary sclerosing cholangitis present with cholestatic patterns. The presence of conjugated hyperbilirubinemia suggests liver disease, and the pattern of enzyme alteration can help differentiate between cholestatic and hepatocellular injury. Nonalcoholic fatty liver disease is a common cause of mild enzyme elevation, with elevated GGT levels in many patients. Autoimmune hepatitis presents with elevated aminotransferases and may require liver biopsy for diagnosis. Hereditary conditions like hemochromatosis and Wilson's disease also present with specific enzyme patterns, requiring genetic testing and liver biopsy. The clinical context, patient history, and laboratory results are crucial in interpreting enzyme alterations. Serum albumin and prothrombin time are often used to assess liver function but are not specific to liver disease. Liver biopsy remains a key diagnostic tool in uncertain cases. The review emphasizes the importance of a systematic approach to evaluating liver enzyme alterations, considering the patient's characteristics, possible causes, and the need for targeted investigations.Liver enzyme alterations are a common clinical challenge, often indicating liver damage or bile flow disturbances. This review provides a guide for clinicians to interpret liver enzyme levels, focusing on hepatocellular and cholestatic patterns. The liver's functional anatomy and pathophysiology are briefly reviewed, with a schematic approach to classify enzyme alterations. The review discusses the most common causes of enzyme changes and initial investigations. Liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are primarily found in the liver, with AST also present in the heart, muscles, and kidneys. ALT is more specific to liver damage. Hepatocellular injury leads to elevated AST and ALT levels, while cholestatic injury affects bile flow, increasing alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT). The severity of enzyme elevation is classified as mild, moderate, or marked, with marked elevations typically indicating acute liver injury. Acute viral hepatitis, ischemic injury, and toxic liver damage present with distinct patterns. For example, in acute viral hepatitis, AST and ALT levels peak before jaundice appears, while in ischemic injury, AST peaks before ALT. The AST/ALT ratio is useful in diagnosing liver disease, with a ratio >1 suggesting chronic liver disease. In alcoholic liver disease, the AST/ALT ratio is often >1, and pyridoxal-5'-phosphate deficiency may affect ALT levels. Cholestatic injury is characterized by elevated ALP and GGT, often with normal or slightly elevated AST. Conditions like primary biliary cirrhosis and primary sclerosing cholangitis present with cholestatic patterns. The presence of conjugated hyperbilirubinemia suggests liver disease, and the pattern of enzyme alteration can help differentiate between cholestatic and hepatocellular injury. Nonalcoholic fatty liver disease is a common cause of mild enzyme elevation, with elevated GGT levels in many patients. Autoimmune hepatitis presents with elevated aminotransferases and may require liver biopsy for diagnosis. Hereditary conditions like hemochromatosis and Wilson's disease also present with specific enzyme patterns, requiring genetic testing and liver biopsy. The clinical context, patient history, and laboratory results are crucial in interpreting enzyme alterations. Serum albumin and prothrombin time are often used to assess liver function but are not specific to liver disease. Liver biopsy remains a key diagnostic tool in uncertain cases. The review emphasizes the importance of a systematic approach to evaluating liver enzyme alterations, considering the patient's characteristics, possible causes, and the need for targeted investigations.