What are the causes of elevated Serum Glutamic-Oxaloacetic Transaminase (SGOT) levels?

Causes of Elevated SGOT (AST)

Elevated SGOT (aspartate aminotransferase/AST) results from hepatocellular injury, muscle damage, or hemolysis, with the most common causes being alcoholic liver disease, non-alcoholic fatty liver disease, viral hepatitis, medication-induced injury, and muscle disorders.

Hepatic Causes

Alcoholic Liver Disease

• AST/ALT ratio >2 is highly suggestive of alcoholic hepatitis and cirrhosis, occurring in 70% of these patients 1, 2
• AST typically elevated 2-6 times upper limit of normal in severe alcoholic hepatitis 1
• AST levels >500 IU/L are uncommon in alcoholic hepatitis alone and should prompt evaluation for other causes 1

Non-Alcoholic Fatty Liver Disease (NAFLD)

• AST:ALT ratio typically <1 in NAFLD, distinguishing it from alcoholic liver disease 3
• Mild to moderate transaminase elevations with preserved synthetic function (normal albumin, bilirubin) 3
• Associated with metabolic syndrome components including obesity, diabetes, and hypertension 3

Viral Hepatitis

• AST:ALT ratio typically <1 in acute viral hepatitis 2
• Can present with AST >3× upper limit of normal, especially with ALT >3× ULN 3
• Hepatitis B, C, and E should be considered with appropriate serologic testing 3

Medication-Induced Liver Injury

• High-dose aspirin therapy can cause anicteric hepatitis with striking AST elevation 4
• Combination of methotrexate and salicylates greatly increases frequency of abnormal liver enzyme values 5
• Chemotherapy can cause hepatic toxicity with elevated AST 1

Glycogen Storage Diseases

• GSD Type I: AST and ALT increased at diagnosis but typically return to normal or near-normal with appropriate treatment 1
• GSD Type III: AST and ALT levels typically higher than GSD I, with elevations >500 U/L commonly seen, and increased levels tend to persist despite treatment 1
• Transaminase elevation accompanied by hepatomegaly and hypoglycemia distinguishes GSDs from other liver diseases 1

Hepatocellular Carcinoma

• AST/ALT ratio greater in hepatocellular carcinoma compared with other liver conditions 6
• Preterminal rises of AST more pronounced than ALT, reflecting tumor-derived enzyme 6

Cirrhosis

• AST/ALT ratio in postnecrotic cirrhosis averages 1.74 ± 0.2 2
• Elevated AST with evidence of synthetic dysfunction (low albumin, prolonged PT, elevated bilirubin) 3

Non-Hepatic Causes

Muscle Disorders

• AST is less specific for liver injury and can be elevated in skeletal muscle disorders, as AST is present in cardiac muscle, skeletal muscle, kidney, and red blood cells 3, 7
• Idiopathic inflammatory myopathies (dermatomyositis/polymyositis) cause AST elevation that coincides with disease activity 8
• Rhabdomyolysis with cardiac involvement elevates AST 1
• Creatine kinase should be measured to differentiate muscle from liver origin of AST elevation 3, 7

Cardiac Causes

• Myocardial infarction causes AST elevation as part of myocardial injury 1
• Cardiac contusion, surgery, or ablation can elevate AST 1

Hemolysis

• Red blood cell disorders and hemolysis can cause AST elevation 3

Other Systemic Conditions

• Strenuous exercise elevates AST 1
• Sepsis and critically ill patients may have elevated AST 1
• Severe acute neurological diseases (stroke, subarachnoid hemorrhage) 1
• Renal failure can be associated with elevated AST 1

Diagnostic Approach

Initial Laboratory Evaluation

• Obtain complete liver panel including ALT, alkaline phosphatase, total and direct bilirubin, albumin, and prothrombin time to assess pattern of injury and synthetic function 7
• Check creatine kinase to rule out muscle disorders as the primary cause 7
• Viral hepatitis serologies (HBsAg, HBcIgM, HCV antibody) 7
• Thyroid function tests to exclude thyroid disorders 7

Pattern Recognition

• AST/ALT ratio >2 strongly suggests alcoholic liver disease 1, 2
• AST/ALT ratio <1 suggests NAFLD, viral hepatitis, or medication-induced injury 3
• Isolated AST elevation without ALT elevation should prompt evaluation for non-hepatic sources, particularly muscle or cardiac origin 7

Imaging

• Abdominal ultrasound as first-line imaging with 84.8% sensitivity and 93.6% specificity for moderate to severe hepatic steatosis 7

Common Pitfalls

• Do not assume isolated AST elevation is hepatic in origin—always check creatine kinase to exclude muscle disorders 7
• AST >2× upper limit of normal can cause false positive liver stiffness measurements in non-invasive fibrosis testing 7
• Normal AST does not exclude significant liver disease, as some conditions primarily elevate ALT 3
• Medication history must include prescription drugs, over-the-counter medications, and herbal supplements 7