Liver Function Tests (LFT)-Why am I having this test?
Liver function tests are done to see how well your liver is working. The proteins and enzymes measured in the test can alert your health care provider to inflammation, damage, or disease in your liver. It is common to have liver function tests:
- When you are taking certain medicines.
- If you have liver disease.
- If you drink a lot of alcohol.
- When you are not feeling well.
- When you have other conditions that may affect your liver.
- During annual physical exams.
- If you have symptoms such as yellowing of the skin (jaundice), abdominal pain, or nausea and vomiting.
The standard battery of tests that is most helpful in assessing liver disease includes total and direct bilirubin, albumin, prothrombin time, and the serum enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and occasionally GGTP and 5′ nucleotidase (5′NT).
Interpretation of these results in concert with careful history taking and a physical examination may suggest a specific type of liver injury, thereby allowing a directed evaluation, risk assessment for surgical procedures, and estimation of prognosis.
What is being tested?
These tests measure various substances in your blood. This may include:
- Alanine transaminase (ALT). This is an enzyme in the liver.
- Aspartate transaminase (AST). This is an enzyme in the liver, heart, and muscles.
- Alkaline phosphatase (ALP). This is a protein in the liver, bile ducts, bone, and other body tissues.
- Total bilirubin. This is a yellow pigment in bile.
- Albumin. This is a protein in the liver.
- Prothrombin time and international normalized ratio (PT and INR). PT measures the time it takes for your blood to clot. INR is a calculation of blood clotting time based on your PT result. It is also calculated based on normal ranges defined by the lab that processed your test.
- Total protein. This includes two proteins, albumin and globulin, found in the blood.
What kind of sample is taken?
A blood sample is required for this test. It is usually collected by inserting a needle into a blood vessel.
How do I prepare for this test?
How you prepare will depend on which tests are being done and the reason for doing them. You may need to:
- Avoid eating for 4–6 hours before the test, or as told by your health care provider.
- Stop taking certain medicines before your blood test, as told by your health care provider.
Tell a health care provider about:
- All medicines you are taking, including vitamins, herbs, eye drops, creams, and over-the-counter medicines.
- Any medical conditions you have.
- Whether you are pregnant or may be pregnant.
How are the results reported?
Your test results will be reported as values. Your health care provider will compare your results to normal ranges that were established after testing a large group of people (reference ranges)
Reference ranges may vary among labs and hospitals. For the substances measured in liver function tests, common reference ranges are:
- Infant: 10–40 international units/L.
- Child or adult: 4–36 international units/L at 37°C or 4–36 units/L (SI units).
- Reference ranges may be higher for older adults.
- Newborn 0–5 days old: 35–140 units/L.
- Child younger than 3 years old: 15–60 units/L.
- 3–6 years old: 15–50 units/L.
- 6–12 years old: 10–50 units/L.
- 12–18 years old: 10–40 units/L.
- Adult: 0–35 units/L or 0–0.58 μkat/L (SI units).
- Reference ranges may be higher for older adults.
- Child younger than 2 years old: 85–235 units/L.
- 2–8 years old: 65–210 units/L.
- 9–15 years old: 60–300 units/L.
- 16–21 years old: 30–200 units/L.
- Adult: 30–120 units/L or 0.5–2.0 μkat/L (SI units).
- Reference ranges may be higher for older adults.
- Newborn: 1.0–12.0 mg/dL or 17.1–205 μmol/L (SI units).
- Child or adult: 0.3–1.0 mg/dL or 5.1–17 μmol/L.
- Premature infant: 3.0–4.2 g/dL.
- Newborn: 3.5–5.4 g/dL.
- Infant: 4.4–5.4 g/dL.
- Child: 4.0–5.9 g/dL.
- Adult: 3.5–5.0 g/dL or 35–50 g/L (SI units).
- 11.0–12.5 seconds; 85%–100%.
- Premature infant: 4.2–7.6 g/dL.
- Newborn: 4.6–7.4 g/dL.
- Infant: 6.0–6.7 g/dL.
- Child: 6.2–8.0 g/dL.
- Adult: 6.4–8.3 g/dL or 64–83 g/L (SI units).
What do the results mean?
Results that are within the reference ranges are considered normal. For each substance measured, results outside the reference range can indicate various health issues.
- Levels above the normal range may indicate liver disease.
- Levels above the normal range may indicate liver disease. Sometimes levels also increase after burns, surgery, heart attack, muscle damage, or seizure.
- Levels above the normal range may be seen in biliary obstruction, liver diseases, bone disease, thyroid disease, tumors, fractures, leukemia, lymphoma, or several other conditions. People with blood type O or B may show higher levels after a fatty meal.
- Levels below the normal range may indicate bone and teeth conditions, malnutrition, protein deficiency, or Wilson’s disease.
- Levels above the normal range may indicate problems with the liver, gallbladder, or bile ducts.
- Levels above the normal range may indicate dehydration. They may also be caused by a diet that is high in protein.
- Levels below the normal range may indicate kidney disease, liver disease, or malabsorption of nutrients.
PT and INR
- Levels above the normal range mean that your blood is clotting slower than normal. This may be due to blood disorders, liver disorders, or low levels of vitamin K.
- Levels above the normal range may be due to infection or other diseases.
- Levels below the normal range may be due to an immune system disorder, bleeding, burns, kidney disorder, liver disease, trouble absorbing or getting nutrients, or other conditions that affect the intestines.
Talk with your health care provider about what your results mean.
Questions to ask your health care provider
Ask your health care provider, or the department that is doing the test:
- When will my results be ready?
- How will I get my results?
- What are my treatment options?
- What other tests do I need?
- What are my next steps?
- Liver function tests are done to see how well your liver is working.
- These tests measure various proteins and enzymes in your blood. The results can alert your health care provider to inflammation, damage, or disease in your liver.
- Talk with your health care provider about what your results mean.
Epidemiologic data suggest that up to 25% of asymptomatic adult Americans have a mild to moderate elevation of aminotransferase levels. The incidental discovery of such abnormalities is currently the most frequent means by which liver disease is first recognized. Whereas up to one third of such patients have no elevation on subsequent testing, many others prove to have steatohepatitis or chronic hepatitis C.
Etiology & Risk Factors
- •AST and ALT have respective blood half-lives of 17 and 47 hr, respectively, and have upper reference range limits of around 40 IU/L.
- •AST is ubiquitously distributed in the body tissues, including the heart and muscle, whereas ALT is found primarily in the liver, although significant amounts are also present in the kidney.
- •With most forms of acute hepatocellular injury, such as hepatitis, AST will be higher than ALT initially because of the higher activity of AST in hepatocytes. Within 24 to 48 hr, particularly if ongoing damage occurs, ALT will become higher than AST, based on its longer half-life. An exception to these observations is seen in acute alcohol-induced hepatocyte injury, as in alcoholic hepatitis. Studies suggest that alcohol induces mitochondrial damage, resulting in the release of mitochondrial AST, which, besides being the predominant form of AST in hepatocytes, has a significantly longer half-life than do extramitochondrial AST and ALT. This frequently results in the disproportionate elevation of AST over ALT, yielding an AST/ALT quotient, also called the DeRitis ratio, of 3 to 4:1 in alcohol-induced liver disease. In chronic hepatocyte injury, mainly in cirrhosis, ALT is more commonly elevated than AST.
causes of elevated serum aminotransferase levels.
Causes of Elevated Serum Aminotransferase Levels
∗Virtually any liver disease can cause moderate aminotransferase elevations (5-15× normal).
From Feldman M, Friedman LS, Brandt LJ: Sleisenger and Fortran’s gastrointestinal and liver disease, ed 10, Philadelphia, 2016, Elsevier.
Chronic, Mild Elevations, ALT > AST (<150 U/L or 5× Normal)
- •α1-Antitrypsin deficiency
- •Autoimmune hepatitis
- •Chronic viral hepatitis (B, C, and D)
- •Medications and toxins
- •Steatosis and steatohepatitis
- •Wilson disease
- •Celiac disease
Severe, Acute Elevations, ALT > AST (>1000 U/L or > 20-25× Normal)
- •Acute bile duct obstruction
- •Acute Budd-Chiari syndrome
- •Acute viral hepatitis
- •Autoimmune hepatitis
- •Drugs and toxins
- •Hepatic artery ligation
- •Ischemic hepatitis
- •Wilson disease
Severe, Acute Elevations, AST > ALT (>1000 U/L or >20-25× Normal)
- •Medications or toxins in a patient with underlying alcohol-associated liver injury
- •Acute rhabdomyolysis
Chronic, Mild Elevations, AST > ALT (<150 U/L, <5× Normal)
- •Alcohol-associated liver injury (AST/ALT >2:1, AST nearly always <300 U/L)
- •Strenuous exercise
Presenting Signs & Symptoms
The majority of patients evaluated for elevated serum aminotransferase levels are asymptomatic and have mild elevations (≤5-fold) identified during routine screening.
- •The first step in the evaluation of mildly elevated serum aminotransferase levels is to repeat the test to confirm persistence of the elevated value. If the aminotransferase level remains elevated,
- The next step is to take a careful history focused on identifying all of the patient’s medications, including over-the-counter (OTC) medications, complementary and alternative medications (CAM), and substances of abuse. Correlating the use of medications temporally with the laboratory abnormalities will sometimes reveal a specific culprit. Almost any medication, including OTC medications, CAM, and substances of abuse, has the potential to elevate serum aminotransferase levels. Relatively common offending agents include NSAIDs, antibiotics, hydroxymethylglutaryl-coenzyme A reductase inhibitors, antiepileptics, and antituberculous medications.
- •The association between use of a medication and liver enzyme elevations is readily established by stopping the medication and observing return of the enzyme levels to normal. Rechallenge with the suspect medication followed by a rise in serum aminotransferase levels is confirmatory but often not undertaken.
- •Muscle disease should also be excluded by obtaining serum creatine kinase and aldolase levels.
- •The next step in the evaluation is to assess the patient for the more common and treatable causes of liver disease, including chronic hepatitis B and C, hemochromatosis, autoimmune hepatitis, Wilson disease, and nonalcoholic fatty liver disease (NAFLD).
- •Although autoimmune hepatitis is commonly considered a disease of young to middle-aged women, it also is seen in men and has been reported in all ethnic groups. The clinical onset of Wilson disease is usually between 5 and 25 yr of age; the diagnosis should be considered initially in all patients age 40 or younger and those older than age 40 with aminotransferase elevations that remain unexplained after other causes are excluded. NAFLD is the most common cause of elevated serum aminotransferase levels in the United States, but there is no specific laboratory test for NAFLD.
- •If testing for the more common causes fails to provide a diagnosis, the less common causes of liver disease, such as α1-antitrypsin deficiency, and extrahepatic causes of persistently elevated liver enzyme levels, such as thyroid disease and celiac disease, should be sought.
- •If testing for these disorders is negative, the decision to perform a liver biopsy is determined by the degree of aminotransferase elevation, with the recognition that the results of the biopsy are unlikely to alter management.
- •The presence of elevated transaminases and jaundice is a common sign of generalized hepatobiliary dysfunction, both acute and chronic. Icteric hepatobiliary disease is readily distinguished from the isolated disorders of bilirubin metabolism because the increase in plasma bilirubin concentration occurs in association with other markers of hepatobiliary disease.
History & Physical Examination
•Some patients with abnormal liver function tests may present with an unremarkable medical history and normal physical exam whereas in others the history and physicalexam will identify the most likely cause of their laboratory abnormality.
Diagnostic workup is aimed primarily at identifying the most likely cause of cirrhosis.
•The history is extremely important:
1.Alcohol abuse: Alcoholic liver disease
2.History of hepatitis B or hepatitis C
3.Obesity, type 2 diabetes mellitus, hyperlipidemia (nonalcoholic steatohepatitis)
4.History of IBD (primary sclerosing cholangitis)
5.History of pruritus, hyperlipoproteinemia, and xanthomas in a middle-aged or elderly woman (primary biliary cholangitis)
6.Erectile dysfunction, diabetes mellitus, hyperpigmentation, arthritis (hemochromatosis)
7.Neurologic disturbances (Wilson disease, hepatolenticular degeneration)
8.Family history of “liver disease” (hemochromatosis [positive family history in 25% of patients], alpha-1-antitrypsin deficiency)
9.History of recurrent episodes of right upper quadrant pain (biliary tract disease)
10.History of blood transfusions, IV drug abuse (hepatitis C)
11.History of repetitive hepatotoxic drug exposure
12.Coexistence of other diseases with immune or autoimmune features (immune thrombocytopenic purpura, myasthenia gravis, thyroiditis, autoimmune hepatitis)
Diagnostic Clues on Physical Examination
- •Skin: Jaundice, palmar erythema, spider angiomata, ecchymosis (thrombocytopenia or coagulation factor deficiency), increased pigmentation (hemochromatosis), xanthomas (primary biliary cirrhosis), and diffuse pruritus. Cutaneous lesions often accompany cirrhosis and can be found in >40% of people with chronic alcoholism
- •Eyes: Kayser-Fleischer rings (corneal copper deposition seen in Wilson disease; best diagnosed with slit lamp examination), scleral icterus
- •Breath: Fetor hepaticus (breath has a sweet musty odor found in cirrhosis with hepatic failure)
- •Chest: Possible gynecomastia in men
- •Abdomen: Tender or nontender hepatomegaly (congestive hepatomegaly), small, nodular liver (cirrhosis), palpable, nontender gallbladder (neoplastic extrahepatic biliary obstruction), palpable spleen (portal hypertension), dilated superficial periumbilical vein (caput medusae), venous hum auscultated over periumbilical veins (portal hypertension), ascites (portal hypertension, hypoalbuminemia), diffuse abdominal tenderness (spontaneous bacterial peritonitis)
- •Rectal examination: Hemorrhoids (portal hypertension), guaiac-positive stools (alcoholic gastritis, bleeding esophageal varices, peptic ulcer disease, bleeding hemorrhoids, portal gastropathy)
- •Genitalia: Testicular atrophy in males (chronic liver disease, hemochromatosis)
- •Extremities: Pedal edema (hypoalbuminemia, anasarca), arthropathy (hemochromatosis), Dupuytren contractures
- •Neurologic: Asterixis (hepatic encephalopathy), choreoathetosis, dysarthria (Wilson disease)
- •The initial evaluation of liver disease involves a battery of blood tests, which can assess hepatic necroinflammation (serum aminotransferases), cholestatic biliary tract dysfunction (alkaline phosphatase, γ-glutamyl transpeptidase), excretory function (bilirubin), and synthetic function (coagulation factors, albumin).
- •In hepatocellular dysfunction caused by viral hepatitis, aminotransferase levels are ele-vated, with the serum ALT level higher than the AST level.
- •In alcoholic hepatitis, AST elevation exceeds that of ALT.
- •In patients with biliary obstruction or cholestatic liver diseases, such as primary biliary cirrhosis or a cholestatic drug reaction, bilirubin and generally alkaline phosphatase levels are elevated.
- •Impairment of synthetic function leads to a decreased serum albumin level over days to weeks.
- •The prothrombin time, expressed as the international normalized ratio (INR), is a more sensitive test of hepatic synthetic function and becomes prolonged within several hours after a major hepatic insult.
- •If laboratory evaluation indicates an obstructive etiology of transaminasemia, imaging studies are necessary to confirm dilated bile ducts, reveal the specific cause for obstruction, exclude differential diagnoses, and guide therapeutic interventions.
- •A transabdominal ultrasound should be ordered as the first study in most cases with suspected biliary tree pathology, including acute cholangitis. An ultrasound is readily available, noninvasive, rapidly performed, and cost effective. Performing an ultrasound is feasible even in severe cases. It has low sensitivity for choledocholithiasis but a very high sensitivity for CBD dilation. It is possible ductal dilation will not be apparent in an early presentation.
- •There are several other primary imaging studies available to evaluate the biliary tree. This includes HIDA scan, which is indicated only to identify cystic duct obstruction.
- •Endoscopic ultrasonography (EUS) has excellent sensitivity for choledocholithiasis. It is helpful for further characterization of a mass as the cause of initial obstruction.
- •Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) have the ability to diagnose a dilated biliary tract. CT can identify the site of obstruction but not necessarily the cause. It provides a global evaluation of abdominal anatomy and pathology. It has a poor sensitivity for intraductal stones. MRCP has greater sensitivity for choledocholithiasis, and it is the ideal test to characterize biliary strictures.
- •After appropriate noninvasive imaging with transabdominal ultrasound, further indicated imaging may consist of modalities that are also therapeutic, including ERCP or percutaneous transhepatic cholangiography (PTC) with percutaneous biliary drain (PBD). Both modalities allow for identification of obstruction location, drainage, culture, and biopsy or brushings.
- •ERCP is often the first invasive procedure performed in patients requiring biliary surgery and/or intervention. ERCP is especially useful in patients with coagulopathies, marked ascites, or in whom intrahepatic lesions, such as multiple hepatic cysts, preclude a safe transhepatic approach.
- •Biopsy is the gold standard to diagnose cirrhosis and is helpful when multiple etiologies are possible that might change management (autoimmune hepatitis, small duct primary sclerosing cholangitis, antimitochondrial antibody–negative primary biliary cholangitis, and infiltrative diseases such as lymphoma, amyloidosis, and granulomatous hepatitis). However, it is generally unnecessary if the clinical picture is highly suggestive of cirrhosis and management would not change. Biopsy can be useful in actively drinking patients with cirrhosis to distinguish between decompensated cirrhosis and cirrhosis with alcoholic hepatitis.
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