1 Liver Function and Injury Patterns

Liver structure and function

The liver receives nutrient-rich blood from the portal vein and oxygen-rich blood from the hepatic artery. At the edge of each liver lobule, branches of these vessels and a bile duct form a portal triad. Blood travels through sinusoids toward a central vein, while bile made by hepatocytes travels through canaliculi toward bile ducts in the opposite direction. Cells near the central vein are relatively vulnerable to reduced oxygen delivery.

Hepatocytes process nutrients and medications, regulate blood glucose and lipid metabolism, produce albumin and many clotting factors, and make bile. They also take up bilirubin, conjugate it to make it water-soluble, and excrete it into bile. Conjugated bilirubin can enter urine; unconjugated bilirubin travels bound to albumin and is not normally excreted in urine.

Interpreting common liver tests

The phrase liver function tests refers to a group of tests, but not every result directly measures liver function. Interpret test patterns alongside symptoms, history, medications, and the laboratory’s reference ranges; results alone usually do not identify a specific disease.

Enzymes and bile flow

ALT and AST are enzymes released with cell injury. Marked elevations relative to ALP suggest a hepatocellular pattern, but enzyme levels do not by themselves show how well the liver is functioning. ALT is more liver-specific; AST can also rise with injury to muscle and other tissues.

A disproportionate rise in ALP can suggest impaired bile flow, or cholestasis. However, ALP also comes from bone and other tissues. GGT can help support a liver or biliary source when ALP is elevated.

Bilirubin

Bilirubin reflects its processing and excretion. Fractionating bilirubin into conjugated and unconjugated forms can help guide interpretation. An increase in unconjugated bilirubin may reflect increased bilirubin production or impaired conjugation; an increase in conjugated bilirubin may occur with liver-cell injury or obstruction.

Protein production and clotting

Albumin is made by the liver. A low level can occur with chronic liver dysfunction, but also with inflammation, malnutrition, kidney protein loss, or fluid overload. Because albumin has a relatively long half-life, its level is less responsive to sudden changes.

PT/INR may become prolonged when production of clotting factors is impaired and can change relatively quickly. Vitamin K deficiency, anticoagulants, and other conditions can also affect it. In cirrhosis, INR alone is not a reliable measure of bleeding risk. Albumin and PT/INR are useful together for assessing protein-production capacity, but neither is specific to liver disease.

Recognizing injury patterns

A hepatocellular pattern has ALT and AST rising more prominently than ALP. Viral hepatitis and ischemic injury are examples; medications and toxins can also cause this pattern.

A cholestatic pattern has a disproportionate rise in ALP, sometimes with bilirubin. It suggests considering impaired bile formation or flow; the cause may be within the liver or in larger bile ducts.

A mixed pattern occurs when aminotransferases and ALP are both elevated without a clear predominance. Drug-induced injury can produce any of these patterns.

Using the R value

The R value classifies the pattern by comparing ALT and ALP elevations with their own laboratory upper limits of normal (ULN):

Use ALT and ALP results from the same sample. Compare each result with its own ULN. An R value greater than $5$ indicates a hepatocellular pattern; a value less than $2$ indicates a cholestatic pattern; and a value from $2$ to $5$ indicates a mixed pattern. The R value classifies the pattern but does not establish its cause or severity.

Worked examples

• With ALT $= 360\ \text{U/L}$, ALT ULN $= 40\ \text{U/L}$, ALP $= 180\ \text{U/L}$, and ALP ULN $= 120\ \text{U/L}$: $R = (360 / 40) / (180 / 120) = 9 / 1.5 = 6$. This is a hepatocellular pattern because $R > 5$.

• With ALT $= 80\ \text{U/L}$, ALT ULN $= 40\ \text{U/L}$, ALP $= 600\ \text{U/L}$, and ALP ULN $= 120\ \text{U/L}$: $R = (80 / 40) / (600 / 120) = 2 / 5 = 0.4$. This is a cholestatic pattern because $R < 2$.

Putting test results together

Use the full pattern and clinical context rather than treating any single result as a diagnosis. For example, elevated ALP with normal ALT and AST does not by itself establish a liver source; GGT can help distinguish a hepatobiliary source from a nonhepatic source such as bone. Likewise, a low albumin alone does not establish chronic liver dysfunction because inflammation, malnutrition, kidney protein loss, and fluid overload can also lower it.

ALT and AST primarily signal cell injury, whereas albumin and PT/INR provide information about protein synthesis. ALP, interpreted with GGT when appropriate, helps identify a cholestatic pattern. Bilirubin gives information about processing and excretion. Consider these results together with symptoms, history, medications, and laboratory reference ranges.