Evaluation of Liver Function

Medical Experts

Contributor

Pandya

Vrajesh K. Pandya, PhD, DABCC

Assistant Professor of Pathology (Clinical), University of Utah

Medical Director, Clinical Chemistry and Toxicology

Contributor

Slev

Patricia R. Slev, PhD, D(ABCC)

Professor of Pathology (Clinical), University of Utah

Section Chief, Immunology; Medical Director, Immunology Core Laboratory, ARUP Laboratories

There is a broad spectrum of laboratory tests used to evaluate liver function and liver damage. Colloquially, these are referred to as liver function tests, although they are not all direct measures of liver function. Liver testing generally includes alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), serum bilirubin, prothrombin time (PT), and albumin tests. ALT and AST are markers of hepatocellular damage, ALP and GGT are markers of cholestasis, PT and albumin are indicators of synthetic function, and bilirubin is a nonspecific marker of liver function. These tests are often available in panels or as standalone assays.

For more information about specific liver-related diseases, refer to the ARUP Consult Viral Hepatitis, Autoimmune Hepatitis, Wilson Disease, Hemochromatosis, Primary Biliary Cholangitis, and Primary Sclerosing Cholangitis topics. For more information about alcohol-induced hepatitis, refer to the ARUP Consult Alcohol Use Biomarkers topic.

Quick Answers for Clinicians

What testing options are available to evaluate patients for liver fibrosis?

Liver biopsy remains the gold standard method to assess liver fibrosis in patients with chronic liver disease. However, noninvasive approaches for staging liver fibrosis have been developed, including imaging and surrogate serum marker assays. These alternative approaches may be useful to assess liver fibrosis in patients who are at high risk for complications from biopsy or in patients with low risk for advanced fibrosis who may not need an invasive liver biopsy to inform medical management. Surrogate serum markers for hepatocellular damage, tissue remodeling, and liver function, along with biological information such as age and sex, can be used to calculate a “fibrosis score” that correlates with the stage of fibrosis that would be determined by a biopsy. Fibrosis scores such as Fibrosis-4 (FIB-4) can be simply calculated using the results from commonly available tests. However, algorithms that combine the results of panels of markers and patient demographic data have become increasingly utilized, as they can improve diagnostic accuracy. Detailed information about ARUP’s noninvasive assays for the evaluation of liver fibrosis can be found here.

What do abnormal liver function test results indicate?

The pattern of abnormal liver function test results may help elucidate the etiology of potential liver disease. For example, some patterns indicate hepatocellular damage, whereas others indicate cholestasis. Detailed information about individual liver function tests can be found in the Laboratory Testing section.

Indications for Testing

Testing may be ordered as part of a routine evaluation or to screen for and monitor liver disease (eg, viral or alcoholic hepatitis). Test selection should be informed by patient history and clinical evaluation. Elevated liver chemistry or function tests should generally be repeated to confirm results before the initiation of exhaustive follow-up testing.

Laboratory Testing

The table below briefly describes the tests most often included in the evaluation of liver function. Commonly, hepatic function tests are offered in panels that include the recommended first-tier tests for liver disease evaluation. The pattern of abnormal test results should be evaluated to help identify additional testing strategies and determine the underlying cause. Some suggestive patterns are included in the Patterns of Liver Test Results section.

Test	Notes
Hepatocellular Damage
AST	Elevated AST may indicate hepatocellular damage The magnitude of AST elevation may vary based on the cause of hepatocellular damage AST is somewhat less specific for liver disease than ALT, as cardiac and skeletal muscle injury may cause AST elevation
ALT	Elevated ALT may indicate hepatocellular damage ALT is generally considered the most specific laboratory test for hepatocellular damage ALT concentrations correlate with increasing BMI The magnitude of ALT elevation may vary based on the cause of hepatocellular damage
AST:ALT ratio	Generally, hepatocellular injury results in an AST:ALT ratio >1 However, alcoholic liver disease usually presents with a ratio of ≥2 This ratio may also be elevated in cases of NAFLD, cirrhosis, or Wilson disease, but the elevation is usually not >2
Cholestasis
ALP	Elevation of ALP is suggestive of cholestasis ALP concentration may also be impacted by age, pregnancy, and sex GGT and/or 5’NT may be useful to identify whether ALP elevation has a hepatic origin
GGT	GGT measurement can be used to confirm the origin of elevated ALP Elevated GGT indicates a hepatic cause of ALP elevation GGT is often used to evaluate alcohol use, but it is nonspecific and may be elevated with diseases such as NAFLD and other hepatobiliary disorders
5’NT	5’NT measurement can be used to confirm the origin of elevated ALP Elevated 5’NT indicates a hepatic cause of ALP elevation, whereas normal 5’NT is very specific for hepatobiliary disease
Nonspecific Marker of Liver Disease
Bilirubin	Elevated bilirubin should be fractionated to indirect (unconjugated) and direct (conjugated) Abnormal concentrations may indicate cholestasis or hepatocellular damage in the presence of other abnormal liver tests
Synthetic Function Tests
Albumin	Liver disease decreases albumin synthesis and decreases serum albumin concentration In the absence of other markers of liver disease, low albumin concentration may be related to malnutrition or protein loss (eg, malabsorption)
PT	Elevated PT that is unresponsive to vitamin K supplementation is suggestive of poor liver function
Fibrosis
Noninvasive fibrosis staging	The degree of fibrosis can be estimated using a combination of clinical and biochemical variables There are several available scoring systems that use different combinations of clinical factors and laboratory tests to calculate a “fibrosis score” that correlates with the severity of liver damage
5’NT, 5’nucleotidase; BMI, body mass index; NAFLD, nonalcoholic fatty liver disease Sources: Lala, 2022; Kwo, 2017; Newsome, 2018

Patterns of Liver Test Results

Hepatocellular Pattern

Elevated ALT and AST concentrations indicate a hepatocellular liver injury. The differential diagnosis may include viral or autoimmune hepatitis, hemochromatosis, alpha 1-antitrypsin deficiency, or Wilson disease. If AST elevation is predominant, consider alcohol-related liver damage or cirrhosis. Although the pattern of AST and ALT may help guide differential diagnosis, additional testing is required for diagnosis. Other liver tests such as bilirubin may also yield elevated results in patients who exhibit a pattern consistent with hepatocellular injury.

Cholestatic Pattern

Increased ALP and GGT concentrations are indicative of cholestasis. To determine if ALP elevation is of hepatic origin, GGT should be evaluated. Cholestatic patterns may be due to hepatobiliary causes such as primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), biliary obstruction, or cholestasis.

Mixed Pattern

If the pattern of elevation includes features of hepatocellular damage and cholestatic injury, the result is said to be “mixed.” A mixed pattern of liver test results accompanied by jaundice is often due to drug-induced liver disease. However, this pattern may also be observed in patients with late-stage acute viral hepatitis or early-stage acute biliary obstruction.