What does a hepatic function panel (liver function tests) check in a 25-year-old male weightlifter with elevated Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT)?

What a Hepatic Function Panel Checks

A hepatic function panel (liver function tests) measures markers of hepatocellular injury (AST, ALT), cholestasis (alkaline phosphatase, GGT), and liver synthetic function (albumin, bilirubin, prothrombin time), though the term "liver function tests" is misleading since most components actually measure hepatocellular damage rather than true liver function. 1, 2

Core Components of the Panel

Markers of Hepatocellular Injury

• ALT (Alanine Aminotransferase) is the most liver-specific enzyme because it exists primarily in hepatocytes with minimal presence in cardiac muscle, skeletal muscle, or red blood cells 3, 4
• AST (Aspartate Aminotransferase) is less specific for liver injury as it is present in cardiac muscle, skeletal muscle, kidneys, brain, and red blood cells, making elevations potentially non-hepatic in origin 3, 5
• Both transaminases provide a "day-by-day account" of hepatocellular injury and death occurring in the liver 6

Markers of Cholestasis (Bile Flow Obstruction)

• Alkaline phosphatase (ALP) estimates the amount of impedance to bile flow and is primarily elevated in cholestatic disorders, though it can also be elevated in bone diseases 1, 6
• GGT (Gamma-Glutamyl Transpeptidase) increases sensitivity for detecting liver disease but at the cost of specificity, and is associated with increased liver and all-cause mortality when significantly elevated 1

Markers of Liver Synthetic Function

• Albumin measures the liver's protein synthesis capacity and decreases in advanced liver disease, serving as an excellent gauge of hepatic synthetic ability 1, 6
• Bilirubin (total and direct) is probably the best test of overall liver function, reflecting the liver's ability to conjugate and excrete bile pigments 1, 6
• Prothrombin time (PT/INR) assesses synthesis of clotting factors made by the liver and is an excellent gauge of hepatic protein synthetic ability 1, 6

Clinical Application in Your Case (25-Year-Old Male Weightlifter)

Non-Hepatic Causes to Consider First

• Muscle injury from weightlifting can significantly elevate AST and ALT due to skeletal muscle damage that may be mistaken for liver injury 3
• Check creatine kinase (CK) levels to confirm muscle origin—if markedly elevated, this indicates rhabdomyolysis or exercise-induced muscle damage rather than liver disease 3, 5
• Intensive exercise, particularly weight lifting, commonly causes acute transaminase elevations in young athletes 3

Hepatic Causes if Muscle Injury Excluded

• NAFLD (Nonalcoholic Fatty Liver Disease) is the most prevalent cause of elevated liver enzymes in developed countries, typically presenting with an AST:ALT ratio <1 3, 4
• Viral hepatitis causes ALT/AST elevation with fluctuating enzyme levels, particularly during reactivation phases 3
• Medication or supplement use accounts for 8-11% of cases with elevated liver enzymes, including over-the-counter products and dietary supplements commonly used by weightlifters 4, 5

Diagnostic Algorithm for Elevated AST/ALT

Calculate the AST:ALT Ratio

• Ratio <1 suggests NAFLD, viral hepatitis, or medication-induced liver injury 1, 3
• Ratio >2:1 is highly suggestive of alcoholic liver disease, with ratios >3 being even more specific 3
• Ratio >1 in the absence of alcohol use indicates advanced fibrosis/cirrhosis 1

Severity Classification

• Mild elevation: <5× upper limit of normal (ULN)—consider NAFLD, dietary changes, or exercise; repeat testing in 2-4 weeks 3, 4
• Moderate elevation: 5-10× ULN—requires prompt but not emergent evaluation 4
• Severe elevation: >10× ULN—requires urgent hepatology referral 4

Initial Workup Beyond the Basic Panel

• Complete liver panel: AST, ALT, alkaline phosphatase, GGT, total and direct bilirubin, albumin, prothrombin time 1, 4
• Creatine kinase to exclude muscle injury as the source 3, 5
• Viral hepatitis serologies: HBsAg, anti-HBc IgM, anti-HCV 1, 4
• Metabolic parameters: fasting glucose/HbA1c, fasting lipid panel to assess for metabolic syndrome 4, 5
• Abdominal ultrasound as first-line imaging with 84.8% sensitivity and 93.6% specificity for detecting moderate to severe hepatic steatosis 4, 5

Common Pitfalls to Avoid

• Do not assume elevated transaminases are always from liver disease—in young weightlifters, muscle injury is a common and often overlooked cause 3
• Normal ALT ranges differ by sex: 29-33 IU/L for males and 19-25 IU/L for females, making even modest elevations clinically significant 4, 5
• Normal transaminases do not exclude significant liver disease—up to 10% of patients with advanced fibrosis may have normal ALT using conventional thresholds 5
• AST is non-specific—elevations can originate from cardiac muscle, skeletal muscle, kidneys, brain, or red blood cells, not just liver 3, 5