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
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.
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.
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.
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
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
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
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 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 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
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
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)
Elevated PT that is unresponsive to vitamin K supplementation is suggestive of poor liver function
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
Patterns of Liver Test Results
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.
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.
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.
ARUP Laboratory Tests
Quantitative Heat Inactivation/Enzymatic Assay
Lala V, Goyal A, Minter DA. Liver function tests. In: StatPearls. StatPearls Publishing; 2022. [Updated: Mar 2022; Accessed: Oct 2022]
Van Dijk AM, Vali Y, Mak AL, et al. Systematic review with meta-analyses: diagnostic accuracy of FibroMeter tests in patients with non-alcoholic fatty liver disease. J Clin Med. 2021;10(13):2910.
Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43(6):1317-1325.
Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846-854.
Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.
Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018;67(1):6-19.