Liver Function Tests

Liver function tests (LFTs), also known as liver enzymes or liver chemistries, generally refer to a panel of serum biochemical studies used to screen for and monitor liver disease. This panel evaluates hepatic components ranging from hepatocellular necrosis and damaged hepatic synthetic capacity to the liver's ability to excrete breakdown products. LFTs also describe a battery of dynamic tests that provide real-time evaluation of liver function, generally by measuring hepatic blood flow, metabolic capacity, or excretory function.

Serum liver biochemical tests can be divided into three groups: (1) markers of hepatocellular injury, including alanine transaminase (ALT) and aspartate transaminase (AST); (2) markers of cholestasis, including alkaline phosphatase (ALP), 5′-nucleotidase, γ-glutamyltransferase (GGT), and bilirubin; and (3) markers of liver synthetic function, including serum albumin and prothrombin time (PT).

In general, the hepatocellular liver enzymes reflect the degree or severity of hepatic necroinflammation. Serum AST and ALT are found in much higher concentrations within hepatocytes than in the circulation. Therefore processes leading to necrosis or swelling of hepatocytes are associated with leakage of these enzymes into the plasma, resulting in increased concentrations. By contrast, elevated serum concentrations of the cholestatic liver enzymes (e.g., ALP) may be attributed to release from damaged hepatocytes or to induction of these enzymes by processes that damage biliary epithelia, such as bile duct obstruction by stones or cholestatic liver disease (e.g., primary biliary cirrhosis, primary sclerosing cholangitis).

Clinicians are routinely tasked with the evaluation of abnormal liver chemistries. In the context of emerging evidence for increased liver-related mortality in individuals with elevated serum ALT and validation of standardized cut-offs for normal values for liver chemistries, clinical practice guidelines currently incorporate new thresholds for normal serum ALT (29–33 IU/L in men, 19–25 IU/L in women) and standardized algorithms to facilitate an individualized approach to evaluation.

Serum concentrations of albumin and bilirubin are more appropriately described as LFTs than liver transaminases; serum albumin is a measure of hepatic synthetic capacity, whereas bilirubin level reflects the uptake, conjugation, and biliary excretion of bilirubin, a breakdown product from senescent red blood cells. PT is a measure of prothrombin synthesis, a vitamin K–dependent process.

The serum bilirubin test is the only blood test that measures the liver's excretory function, including uptake, conjugation, and biliary excretion. Other tests examine the liver's ability to perform specific metabolic functions and often involve administration of a compound, after which its metabolite can be measured in the serum, breath, or urine. These metabolic LFTs are more sensitive for hepatic dysfunction than the serum bilirubin test, but they may lack specificity. Nevertheless, these tests have proven useful in certain patients, such as those with compensated cirrhosis being considered for liver resection or surgery to decompress portal hypertension and whose hepatic functional reserve must be determined.