Liver function tests
| Liver function tests | |
|---|---|
| ICD-10-PCS | K-70 to K-77 |
| MeSH | D008111 |
| MedlinePlus | 003436 |
Liver function tests (LFTs or LFs) are groups of blood tests that give information about the state of a patient's liver.[1] These tests include prothrombin time (PT/INR), aPTT, albumin, bilirubin (direct and indirect), and others. Liver transaminases (AST or SGOT and ALT or SGPT) are useful biomarkers of liver injury in a patient with some degree of intact liver function.[2][3][4] Most liver diseases cause only mild symptoms initially, but these diseases must be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed on a patient's blood sample. Some tests are associated with functionality (e.g., albumin), some with cellular integrity (e.g., transaminase), and some with conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline phosphatase). Several biochemical tests are useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used to detect the presence of liver disease, distinguish among different types of liver disorders, gauge the extent of known liver damage, and follow the response to treatment. Some or all of these measurements are also carried out (usually about twice a year for routine cases) on those individuals taking certain medications, such as anticonvulsants, to ensure the medications are not damaging the person's liver.
Standard liver panel
 | This section needs additional citations for verification. (November 2008) |
Although example reference ranges are given, these will vary depending on age, gender, ethnicity, method of analysis, and units of measurement. Individual results should always be interpreted using the reference range provided by the laboratory that performed the test.
Albumin
| Reference range |
| 3.5 to 5.3 g/dL |
Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein (the remaining from globulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the urine. The consequence of low albumin can be edema since the intravascular oncotic pressure becomes lower than the extravascular space. An alternative to albumin measurement is prealbumin, which is better at detecting acute changes (half-life of albumin and prealbumin is about 2 weeks and about 2 days, respectively).
Aspartate transaminase
| Reference range |
| 6-40 IU/L[5] |
AST, also called serum glutamic oxaloacetic transaminase or aspartate aminotransferase, is similar to ALT in that it is another enzyme associated with liver parenchymal cells. It is raised in acute liver damage, but is also present in red blood cells, and cardiac and skeletal muscle, so is not specific to the liver. The ratio of AST to ALT is mostly useful in differentiating between causes of liver damage.[6][7] Elevated AST levels are not specific for liver damage, and AST has also been used as a cardiac marker. When the AST is higher than ALT, a muscle source of these enzymes should be considered. For example, muscle inflammation due to dermatomyositis may cause AST>ALT. This is a good reminder that AST and ALT are not good measures of liver function because they do not reliably reflect the synthetic ability of the liver and they may come from tissues other than liver (such as muscle).
Transaminases
AST/ALT elevations instead of ALP elevations favor liver cell necrosis as a mechanism over cholestasis. When AST and ALT are both over 1000 IU/L, the differential can include acetaminophen toxicity, shock, or fulminant liver failure. When AST and ALT are greater than three times normal but not greater than 1000 IU/L, the differential can include alcohol toxicity, viral hepatitis, drug-induced level, liver cancer, sepsis, Wilson's disease, post-transplant rejection of liver, autoimmune hepatitis, and steatohepatitis (nonalcoholic). AST/ALT levels elevated minorly may be due to rhabdomyolysis, among many possibilities.
Alkaline phosphatase
| Reference range |
| 30 to 120 IU/L[8] |
Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the liver. ALP levels in plasma rise with large bile duct obstruction, intrahepatic cholestasis, or infiltrative diseases of the liver. ALP is also present in bone and placental tissue, so it is higher in growing children (as their bones are being remodelled) and elderly patients with Paget's disease. In the third trimester of pregnancy, ALP is about two to three times higher.
Biliary tract disease produces relatively greater increases in ALP than increases in ALT, AST, or LD. ALP is associated with the plasma membrane of hepatocytes adjacent to the biliary canaliculus. Obstruction or inflammation of the biliary tract results in an increased concentration of the ALP in the circulation. Similar to ALT and AST, ALP is not specific for biliary tract disease. ALP is released by osteoblasts, the ileum, and the placenta. ALP is elevated: 1) in children 2- to 3-fold over adults because the child's skeleton is growing, 2) with bone disease involving osteoblasts (e.g., metastatic cancer or following a fracture), 3) in hyperparathyroidism where parathyroid hormone stimulates osteoblasts through a series of steps that enhances bone resorption (e.g., parathyroid adenoma, hyperplasia, or secondary hyperparathyroidism from vitamin D deficiency or renal disease), 4) in cases of ileal disease, and 5) during the third trimester of pregnancy because the placental isoenzyme is elevated.
Total bilirubin
| Reference range |
| 0.1–1.0 mg/dL |
Measurement of total bilirubin includes both unconjugated and conjugated bilirubin. Unconjugated bilirubin is a breakdown product of heme (a part of hemoglobin in red blood cells). It is very hydrophobic and is mainly transported bound to albumin circulating in the blood. Addition of high-concentration hydrophobic drugs (certain antibiotics, diuretics) and high free fatty acids can cause elevated unconjugated bilirubin. Heme can also come from myoglobin, found mostly in muscle, cytochromes, found mostly in mitochondria, catalase, peroxidase, and nitric oxide synthase. The liver is responsible for clearing the blood of unconjugated bilirubin, and about 30% of it is taken up by a normal liver on each pass of the blood through the liver by the following mechanism: bilirubin is taken up into hepatocytes, 'conjugated' (modified to make it water-soluble) by UDP-glucuronyl-transferase, and secreted into the bile by CMOAT (MRP2), which is excreted into the intestine. In the intestine, conjugated bilirubin may be metabolized by colonic bacteria, eliminated, or reabsorbed. Metabolism of bilirubin into urobilinogen followed by reabsorption of urobilinogen accounts for the yellow color of urine, as urine contains a downstream product of urobilinogen. Further metabolism of urobilinogen into stercobilin while in the bowels accounts for the brown color of stool. Thus, having white or clay-colored stool is an indicator for a blockage in bilirubin processing and thus potential liver dysfunction or cholestasis.
Increased total bilirubin (TBIL) causes jaundice, and can indicate a number of problems:
- 1. Prehepatic: Increased bilirubin production can be due to a number of causes, including hemolytic anemias and internal hemorrhage.
- 2. Hepatic: Problems with the liver are reflected as deficiencies in bilirubin metabolism (e.g., reduced hepatocyte uptake, impaired conjugation of bilirubin, and reduced hepatocyte secretion of bilirubin). Some examples would be cirrhosis and viral hepatitis.
- 3. Posthepatic: Obstruction of the bile ducts is reflected as deficiencies in bilirubin excretion. (Obstruction can be located either within the liver or in the bile duct).
Direct bilirubin
| Reference range |
| 0.1–0.4 mg/dL |
The diagnosis is narrowed down further by evaluating the levels of direct bilirubin.
- If direct (conjugated) bilirubin is normal, then the problem is an excess of unconjugated bilirubin (indirect bilirubin), and the location of the problem is upstream of bilirubin conjugation in the liver. Hemolysis, or internal hemorrhage can be suspected.
- If direct bilirubin is elevated, then the liver is conjugating bilirubin normally, but is not able to excrete it. Bile duct obstruction by gallstones, hepatitis, cirrhosis or cancer should be suspected.
Congenital bilirubin disorders
About 5% of the population has Gilbert's syndrome, a mutation (or variation) in the UDP-glucuronyl-transferase promotor that manifests itself as jaundice when the individual is stressed (i.e. starves). Autosomal recessive knockouts of UDP-glucuronyl-transferase can lead to Crigler-Najjar syndrome and elevations of unconjugated bilirubin. Defects in CMOAT (MRP2) results in Dubin-Johnson syndrome and elevations of conjugated bilirubin.
High bilirubin in neonates
Neonates are especially vulnerable to high bilirubin levels due to an immature blood-brain barrier that predisposes them to kernicterus/bilirubin encephalopathy, which can result in permanent neurological damage. Neonates also have a low amount of functional UDP-glucuronyl-transferase and can have elevated unconjugated bilirubin, since conjugation is limited. So, newborns are often treated with blue light (420-470 nm) to turn the hydrophobic, albumin-binding unconjugated bilirubin into a form that is more hydrophilic and able to be secreted in urine, sparing the neonate's brain.
Gamma glutamyl transpeptidase
| Reference range |
| 0 to 42 IU/L[8] |
Although reasonably specific to the liver and a more sensitive marker for cholestatic damage than ALP, gamma glutamyl transpeptidase (GGT) may be elevated with even minor, subclinical levels of liver dysfunction. It can also be helpful in identifying the cause of an isolated elevation in ALP (GGT is raised in chronic alcohol toxicity).
The proximal convoluted tubule of the kidney, the liver, the pancreas, and the intestine are sources of GGT, in decreasing order of tissue concentration. Within the cell, GGT is located in microsomes and along the biliary tract plasma membrane, GGT is more commonly measured than 5’-NT because GGT testing is widely available on a variety of laboratory instruments. GGT is typically not elevated with bone disease. Combined elevations of ALP and GGT are compatible with biliary tract disease. However, if the ALP is elevated to a far greater extent than the GGT (or the GGT is normal), ALP sources other than the biliary tract, such as bone, must be investigated. GGT elevations occur in response to alcohol use and anticonvulsants, as GGT is induced by such agents.
INR
Prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status.
Other tests
Other tests commonly requested alongside LFTs include
5' Nucleotidase
5' Nucleotidase (5'NTD) is another test specific for cholestasis or damage to the intra- or extrahepatic biliary system, and in some laboratories, is used as a substitute for GGT for ascertaining whether an elevated ALP is of biliary or extrabiliary origin.
Coagulation test
The liver is responsible for the production of coagulation factors. INR measures the speed of a particular pathway of coagulation, comparing it to normal. Increased levels of INR means blood is taking more time than usual to clot. The INR increases only if the liver is so damaged that synthesis of vitamin K-dependent coagulation factors has been impaired; it is not a sensitive measure of liver function.
It is very important to normalize the INR before operating on people with liver problems (usually by transfusion with blood plasma containing the deficient factors), as they could bleed excessively.
Serum glucose
The serum glucose test, abbreviated as "BG" or "Glu", measures the liver's ability to produce glucose (gluconeogenesis); it is usually the last function to be lost in the setting of fulminant liver failure.
Lactate dehydrogenase
Lactate dehydrogenase (LDH) is found in many body tissues, including the liver. Elevated levels of LDH may indicate liver damage.[citation needed] LDH isotype-1 (or cardiac) is used for estimating damage to cardiac tissue, although troponin and creatine kinase tests are more preferred.[9]
See also
References
- ^ Lee, Mary (10 March 2009). Basic Skills in Interpreting Laboratory Data. ASHP. pp. 259–. ISBN 978-1-58528-180-0. Retrieved 5 August 2011.
- ^ Johnston DE (1999). "Special considerations in interpreting liver function tests". Am Fam Physician. 59 (8): 2223–30. PMID 10221307.
- ^ McClatchey, Kenneth D. (2002). Clinical laboratory medicine. Lippincott Williams & Wilkins. pp. 288–. ISBN 978-0-683-30751-1. Retrieved 5 August 2011.
- ^ Mengel, Mark B.; Schwiebert, L. Peter (2005). Family medicine: ambulatory care & prevention. McGraw-Hill Professional. pp. 268–. ISBN 978-0-07-142322-9. Retrieved 5 August 2011.
- ^ "http://www.gpnotebook.co.uk/simplepage.cfm?ID=322240579"
- ^ Nyblom H, Berggren U, Balldin J, Olsson R (2004). "High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking". Alcohol Alcohol. 39 (4): 336–339. doi:10.1093/alcalc/agh074. PMID 15208167.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Nyblom H, Björnsson E, Simrén M, Aldenborg F, Almer S, Olsson R (September 2006). "The AST/ALT ratio as an indicator of cirrhosis in patients with PBC". Liver Int. 26 (7): 840–845. doi:10.1111/j.1478-3231.2006.01304.x. PMID 16911467.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b MedlinePlus Encyclopedia: Liver function tests
- ^ Nageh T, Sherwood RA, Harris BM, Byrne JA, Thomas MR (2003). "Cardiac troponin T and I and creatine kinase-MB as markers of myocardial injury and predictors of outcome following percutaneous coronary intervention". International journal of cardiology. 92 (2–3): 285–293. doi:10.1016/S0167-5273(03)00105-0. PMID 14659867.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
External links
- Liver Function Tests at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Liver Function Tests at Lab Tests Online
- Overview at Mayo Clinic
- Abnormal Liver Function Tests
- Overview of liver enzymes