Clinical meaning
Liver function tests (LFTs) comprise a panel of serum biomarkers that reflect hepatocellular integrity, biliary function, and synthetic capacity of the liver. Understanding the patterns of elevation guides the NP toward accurate differential diagnosis and appropriate workup.
Hepatocellular enzymes: Alanine aminotransferase (ALT) is predominantly found in hepatocytes and is the most specific marker of hepatocellular injury. Aspartate aminotransferase (AST) is found in hepatocytes, cardiac muscle, skeletal muscle, kidney, and brain, making it less liver-specific. Both are released into the serum when hepatocyte membranes are damaged. The AST:ALT ratio provides diagnostic information: ratio <1 in most hepatitis (viral, drug-induced); ratio >2:1 strongly suggests alcoholic liver disease (alcohol preferentially damages mitochondria where AST is concentrated, and chronic alcohol use depletes pyridoxal-5-phosphate [vitamin B6] needed for ALT synthesis); ratio >3:1 is highly suggestive of alcoholic hepatitis.
Cholestatic enzymes: Alkaline phosphatase (ALP) is present in bile duct epithelium, bone, placenta, and intestine. Gamma-glutamyl transferase (GGT) is found in bile duct epithelium and hepatocytes. Elevation of both ALP and GGT together indicates hepatobiliary origin (cholestatic pattern). Isolated ALP elevation without GGT elevation suggests bone origin (growth, Paget disease, bone metastases, vitamin D deficiency). GGT alone is highly sensitive but non-specific; it is induced by alcohol and certain medications (phenytoin, barbiturates).
Synthetic function markers: Albumin (half-life 20 days) reflects chronic synthetic capacity -- low albumin suggests chronic liver disease, not acute hepatitis. Prothrombin time (PT)/INR reflects acute synthetic function because clotting factors (II, VII, IX, X, fibrinogen) have short half-lives (6 hours for factor VII); elevated INR in acute liver injury indicates loss of synthetic function and is a prognostic marker of severity. Bilirubin metabolism involves hepatocyte uptake, conjugation (glucuronidation), and biliary excretion; elevation can reflect hemolysis (unconjugated/indirect predominant), hepatocellular dysfunction (mixed), or biliary obstruction (conjugated/direct predominant).