Liver enzymes and liver function tests (LFTs) are common lab tests drawn in both primary care and acute care settings. They are used to gauge liver impairment, evaluate the degree of liver injury, and monitor the progression of liver disease and its response to treatment (Saiman, 2023). Approximately 1 to 9% of asymptomatic patients are found to have elevated liver enzymes when screened with standard LFT panels (Malakouti, Kataria, Ali & Schenker, 2017). These elevations may be short-term, resolving after several weeks, however high levels can also signal acute injury and chronic disease.
Varying Reference Ranges
When assessing your patient’s bloodwork, it’s important to remember that reference ranges will vary by laboratory. In addition, certain ranges will differ between males and females and may be higher in individuals with an increased body mass index (Lala, Zubair & Minter, 2023).
|Liver Test (Friedman, 2022a)
|Liver Enzymes: found in the liver and other tissues; elevated levels indicate liver injury and disease.
|Alanine aminotransferase (ALT)
||Male: 29–33 units/Liter (L)
Female: 19–25 units/L
|Aspartate aminotransferase (AST)
||Male: 10–40 units/L
Female: 9–32 units/L
|Alkaline phosphatase (ALP)
||Male: 45–115 units/L
Female: 30–100 units/L
|Gamma-glutamyl transpeptidase (GGT)
||Male: 8–61 units/L
Female: 5–36 units/L
|5’-nucleotidase (Friedman, 2022b)
||0.3–3.2 Bodansky units
|Lactate dehydrogenase (LDH) (UpToDate, n.d.)
|Liver Function Tests (LFTs): indication of hepatic function, the ability to produce protein as well as fibrinogen and vitamin K-dependent clotting factors II (prothrombin), VII, IX, and X.
|Total protein (UpToDate, n.d.)
||5.5–9.0 g/100 mL
||3.5–5 g/100 mL
|Prothrombin time (PT)
|International normalized ratio (INR) (Shikdar, Vashisht, & Bhattacharya, 2023)
||Approximately 1.0 second
|Bilirubin: the pigment in bile produced from the breakdown of blood proteins (hemoglobin) in aging red blood cells. Levels will indicate bile duct injury or obstruction.
|Bilirubin, total (UpToDate, n.d.)
|Direct bilirubin, conjugated (UpToDate, n.d.)
|Indirect bilirubin, unconjugated (UpToDate, n.d.)
General Interpretation of Liver Enzymes and LFTs
Abnormal liver enzymes are assessed in three parts (Friedman, 2022a; Lala, Zubair & Minter, 2023; Melendez-Rosado, et al., 2018): the pattern of elevation, the degree of elevation, and clinical risk factors.
Pattern of Elevation
The pattern of elevation provides information on the source of the damage (i.e., the liver or bile duct).
- Hepatocellular pattern
- Elevated AST and/or ALT out of proportion to ALP signifies damage to the liver tissue.
- Bilirubin may be elevated; albumin and PT may be abnormal.
- ALT-predominant indicates acute or chronic viral hepatitis, steatohepatitis, acute Budd-Chiari syndrome, ischemic hepatitis, autoimmune, hemochromatosis, medications/toxins, alpha1-antitrypsin deficiency, Wilson disease, or celiac disease.
- AST-predominant indicates alcohol-related liver disease, steatohepatitis, cirrhosis, or non-hepatic causes (hemolysis, myopathy, thyroid disease, exercise).
- Cholestatic pattern
- Elevated ALP, GGT, and bilirubin out of proportion to AST and ALT signifies impaired bile production/excretion or bile duct obstruction.
- Albumin and PT may be abnormal.
- Hepatobiliary causes include bile duct obstruction, primary biliary cirrhosis, primary sclerosing cholangitis, medication-induced, infiltrating disease of liver (sarcoidosis, amyloidosis, lymphoma), cystic fibrosis, hepatic metastasis, or cholestasis.
- Non-hepatic causes include bone disease, pregnancy, chronic renal failure, lymphoma, congestive heart failure, infection, or inflammation.
- Mixed injury pattern
- Elevated ALP and AST/ALT levels
- Isolated hyperbilirubinemia
- Elevated bilirubin and normal ALP, AST, and ALT levels
- Caused by increased bilirubin production (prehepatic), decreased liver uptake or conjugation (hepatic), or decreased biliary excretion and duct obstruction (posthepatic)
Degree of elevation
The degree of elevation will vary depending on the cause of injury.
- Borderline: AST and/or ALT elevation is less than 2 times the upper limit of normal (ULN).
- Mild: AST and/or ALT elevation is 2 to 5 times the ULN.
- Moderate: AST and/or ALT elevation is 5 to 15 times the ULN.
- Severe: AST and/or ALT elevation is greater than 15 times the ULN.
- Massive: AST and/or ALT is greater than 10,000 units/L.
Clinical risk factors
- Medical history of diabetes mellitus, hyperlipidemia, obesity, inflammatory bowel disease, celiac, thyroid disorders, autoimmune disorders, heart failure, or acquired muscle disorders.
- Family history of genetic liver disorders such as Wilson disease, alpha-1 antitrypsin deficiency, or hereditary hemochromatosis.
- Social history including travel, alcohol intake, or sexual behavior.
- Medications such as acetaminophen, amiodarone, antibiotics (azithromycin, amoxicillin, nafcillin, rifampin, tetracycline), antifungals (ketoconazole), antivirals (valacyclovir, ritonavir), antidepressants (fluoxetine), antipsychotics (risperidone), anti-seizure drugs (valproic acid, phenytoin), non-steroidal anti-inflammatory drugs (NSAIDs), methotrexate, tuberculosis drugs (isoniazid, pyrazinamide, rifampin), oral contraceptives, statins, anabolic steroids, or herbal medications.
As you review these laboratory findings, always compare the results to the patient’s physical exam while assessing for signs of chronic liver disease. Physical exam findings suggesting liver disease include (Friedman, 2022a):
- Hepatic encephalopathy/neurologic changes
- Increased jugular venous pressure
- Muscle wasting
- Parotid gland enlargement
- Peripheral edema
- Testicular atrophy
Recognizing and understanding the various patterns in liver enzymes and LFTs along with a thorough assessment of the patient’s medical history, risk factors, and physical exam will help you determine whether an elevation in these lab values is a cause for concern requiring additional work-up or a normal variant that can be watched over time.