Elevated transaminases

Last updated
Elevated transaminases
Alanine amino transferase.png
Alanine transaminase is one of the two transaminases measured (Aspartate transaminase is the other).

In medicine, the presence of elevated transaminases, commonly the transaminases alanine transaminase (ALT) and aspartate transaminase (AST), may be an indicator of liver dysfunction. [1] [2] Other terms include transaminasemia, [3] and elevated liver enzymes (though they are not the only enzymes in the liver). Normal ranges for both ALT and AST vary by gender, age, and geography and are roughly 8-40 U/L (0.14-0.67 μkal/L). [4] Mild transaminesemia refers to levels up to 250 U/L. [1] Drug-induced increases such as that found with the use of anti-tuberculosis agents such as isoniazid are limited typically to below 100 U/L for either ALT or AST. Muscle sources of the enzymes, such as intense exercise, are unrelated to liver function and can markedly increase AST and ALT. [5] Cirrhosis of the liver or fulminant liver failure secondary to hepatitis commonly reach values for both ALT and AST in the >1000 U/L range; however, many people with liver disease have normal transaminases. [6] [7] Elevated transaminases that persist less than six months are termed "acute" in nature, and those values that persist for six months or more are termed "chronic" in nature.

Contents

Pathophysiology

The liver has transaminases to synthesize and break down amino acids and to convert energy storage molecules. The concentrations of these transaminases in the serum (the non-cellular portion of blood) are normally low. However, if the liver is damaged, the liver cell (hepatocyte) membrane becomes more permeable and some of the enzymes leak out into the blood circulation.[ citation needed ]

The two transaminases commonly measured are alanine transaminase (ALT) and aspartate transaminase (AST). [1] These levels previously were called serum glutamate-pyruvate transaminase (SGPT) and serum glutamate-oxaloacetate transaminase (SGOT). Elevated levels are sensitive for liver injury, meaning that they are likely to be present if there is injury. However, they may also be elevated in other conditions such as thyroid disorders, celiac disease, and muscle disorders. [8]

ALT is usually found only in the liver. AST is most commonly found in the liver, but also in significant amounts in heart (cardiac) and skeletal muscle.[ citation needed ]

Measurement of ALT and AST were used in diagnosing heart attacks, although they have been replaced by newer enzyme and protein tests that are more specific for cardiac damage.[ citation needed ]

Possible causes for high ALT levels are liver inflammation (hepatitis A, B, C, infectious mononucleosis, acute viral fever, alcohol, pancreatic disorder), injury to muscles (trauma, myocardial infarction, congestive heart failure, acute kidney failure), and many toxins and drugs. [9]

Role in diagnosis

In general, any damage to the liver will cause medium elevations in these transaminases, but diagnosis requires synthesis of many pieces of information, including the patient's history, physical examination, and possibly imaging or other laboratory examinations. However, very high elevations of the transaminases suggests severe liver damage, such as viral hepatitis, liver injury from lack of blood flow, or injury from drugs or toxins. Most disease processes cause ALT to rise higher than AST; AST levels double or triple that of ALT are consistent with alcoholic liver disease.[ citation needed ]

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 when other sources may influence AST and/or ALT, because they do not reliably reflect the synthetic ability of the liver, and they may come from tissues other than liver (such as muscle). [10] For example, intense exercise such as weight lifting can increase ALT to 50-200 U/L, and AST to 100-1000 U/L for the week following the exercise. [5]

Magnitude of AST and ALT elevations

The magnitude of AST and ALT elevations vary depending on the cause of the increase, such as intensity of recent muscular exertion or type of hepatocellular injury. The following refer to the "upper reference limit" (URL), also known as the "upper limit of normal" (ULN), which depend on the source and are typically 40-50 U/L (0.67-0.83 μkal/L) for both AST and ALT. While values vary between individuals, the following are typical AST and ALT patterns: [11] [12] [13] [14]

See also

Related Research Articles

<span class="mw-page-title-main">Clinical chemistry</span> Area of clinical pathology that is generally concerned with analysis of bodily fluids

Clinical chemistry is a division in medical laboratory sciences focusing on qualitative tests of important compounds, referred to as analytes or markers, in bodily fluids and tissues using analytical techniques and specialized instruments. This interdisciplinary field includes knowledge from medicine, biology, chemistry, biomedical engineering, informatics, and an applied form of biochemistry.

<span class="mw-page-title-main">Jaundice</span> Abnormal pigmentation symptom for disease of the liver

Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin and sclera due to high bilirubin levels. Jaundice in adults is typically a sign indicating the presence of underlying diseases involving abnormal heme metabolism, liver dysfunction, or biliary-tract obstruction. The prevalence of jaundice in adults is rare, while jaundice in babies is common, with an estimated 80% affected during their first week of life. The most commonly associated symptoms of jaundice are itchiness, pale feces, and dark urine.

Liver function tests, also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin time (aPTT), albumin, bilirubin, and others. The liver transaminases aspartate transaminase and alanine transaminase are useful biomarkers of liver injury in a patient with some degree of intact liver function.

<span class="mw-page-title-main">Alanine transaminase</span> Mammalian protein

Alanine transaminase (ALT) is a transaminase enzyme. It is also called alanine aminotransferase and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first characterized in the mid-1950s by Arthur Karmen and colleagues. ALT is found in plasma and in various body tissues but is most common in the liver. It catalyzes the two parts of the alanine cycle. Serum ALT level, serum AST level, and their ratio are routinely measured clinically as biomarkers for liver health.

<span class="mw-page-title-main">Alcoholic liver disease</span> Medical condition

Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.

<span class="mw-page-title-main">Gamma-glutamyltransferase</span> Class of enzymes

Gamma-glutamyltransferase is a transferase that catalyzes the transfer of gamma-glutamyl functional groups from molecules such as glutathione to an acceptor that may be an amino acid, a peptide or water. GGT plays a key role in the gamma-glutamyl cycle, a pathway for the synthesis and degradation of glutathione as well as drug and xenobiotic detoxification. Other lines of evidence indicate that GGT can also exert a pro-oxidant role, with regulatory effects at various levels in cellular signal transduction and cellular pathophysiology. This transferase is found in many tissues, the most notable one being the liver, and has significance in medicine as a diagnostic marker.

<span class="mw-page-title-main">Hepatotoxicity</span> Liver damage caused by a drug or chemical

Hepatotoxicity implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdrawn from the market after approval.

<span class="mw-page-title-main">Alcoholic hepatitis</span> Medical condition

Alcoholic hepatitis is hepatitis due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8–10 drinks per day. It is usually found in association with fatty liver, an early stage of alcoholic liver disease, and may contribute to the progression of fibrosis, leading to cirrhosis. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice, ascites, fatigue and hepatic encephalopathy. Mild cases are self-limiting, but severe cases have a high risk of death. Severity in alcoholic hepatitis is determined several clinical prediction models such as the Maddrey's Discriminant Function and the MELD score.

HELLP syndrome is a complication of pregnancy; the acronym stands for hemolysis, elevated liver enzymes, and low platelet count. It usually begins during the last three months of pregnancy or shortly after childbirth. Symptoms may include feeling tired, retaining fluid, headache, nausea, upper right abdominal pain, blurry vision, nosebleeds, and seizures. Complications may include disseminated intravascular coagulation, placental abruption, and kidney failure.

<span class="mw-page-title-main">Aspartate transaminase</span> Enzyme involved in amino acid metabolism

Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase, is a pyridoxal phosphate (PLP)-dependent transaminase enzyme that was first described by Arthur Karmen and colleagues in 1954. AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in amino acid metabolism. AST is found in the liver, heart, skeletal muscle, kidneys, brain, red blood cells and gall bladder. Serum AST level, serum ALT level, and their ratio are commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.

<span class="mw-page-title-main">Transaminase</span> Class of enzymes

Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins.

<span class="mw-page-title-main">Glycogen storage disease type 0</span> Medical condition

Glycogen storage disease type 0 is a disease characterized by a deficiency in the glycogen synthase enzyme (GSY). Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified as a glycogen storage disease because it is another defect of glycogen storage and can cause similar problems. There are two isoforms (types) of glycogen synthase enzyme; GSY1 in muscle and GSY2 in liver, each with a corresponding form of the disease. Mutations in the liver isoform (GSY2), causes fasting hypoglycemia, high blood ketones, increased free fatty acids and low levels of alanine and lactate. Conversely, feeding in these patients results in hyperglycemia and hyperlactatemia.

<span class="mw-page-title-main">Cahill cycle</span> Metabolic pathway for transport of energy into and removal of ammonia from muscles

The Cahill cycle, also known as the alanine cycle or glucose-alanine cycle, is the series of reactions in which amino groups and carbons from muscle are transported to the liver. It is quite similar to the Cori cycle in the cycling of nutrients between skeletal muscle and the liver. When muscles degrade amino acids for energy needs, the resulting nitrogen is transaminated to pyruvate to form alanine. This is performed by the enzyme alanine transaminase (ALT), which converts L-glutamate and pyruvate into α-ketoglutarate and L-alanine. The resulting L-alanine is shuttled to the liver where the nitrogen enters the urea cycle and the pyruvate is used to make glucose.

Carbohydrate-deficient transferrin is a laboratory test used to help detect heavy ethanol consumption.

<span class="mw-page-title-main">GOT1</span> Cytoplasmic enzyme involved in amino acid metabolism

Aspartate aminotransferase, cytoplasmic is an enzyme that in humans is encoded by the GOT1 gene.

<span class="mw-page-title-main">Ischemic hepatitis</span> Medical condition

Ischemic hepatitis, also known as shock liver, is a condition defined as an acute liver injury caused by insufficient blood flow to the liver. The decreased blood flow (perfusion) to the liver is usually due to shock or low blood pressure. However, local causes involving the hepatic artery that supplies oxygen to the liver, such as a blood clot in the hepatic artery, can also cause ischemic hepatitis.

The AST/ALT ratio or De Ritis ratio is the ratio between the concentrations of two enzymes, aspartate transaminase (AST) and alanine transaminase, aka alanine aminotransferase (ALT), in the blood of a human or animal. It is used as one of several liver function tests, and measured with a blood test. It is sometimes useful in medical diagnosis for elevated transaminases to differentiate between causes of liver damage, or hepatotoxicity.

<span class="mw-page-title-main">Elevated alkaline phosphatase</span> Medical condition

Elevated alkaline phosphatase occurs when levels of alkaline phosphatase (ALP) exceed the reference range. This group of enzymes has a low substrate specificity and catalyzes the hydrolysis of phosphate esters in a basic environment. The major function of alkaline phosphatase is transporting chemicals across cell membranes. Alkaline phosphatases are present in many human tissues, including bone, intestine, kidney, liver, placenta and white blood cells. Damage to these tissues causes the release of ALP into the bloodstream. Elevated levels can be detected through a blood test. Elevated alkaline phosphate is associated with certain medical conditions or syndromes. It serves as a significant indicator for certain medical conditions, diseases and syndromes.

FibroTest, known as FibroSure in the US, is a biomarker test that uses the results of six blood serum tests to generate a score that is correlated with the degree of liver damage in people with a variety of liver diseases. FibroTest has the same prognostic value as a liver biopsy. FibroSure uses quantitative results of five serum biochemical markers, α2-macroglobulin, haptoglobin, apolipoprotein A1, bilirubin, gamma glutamyl transpeptidase (GGT), with a patient’s age and gender to generate a measure of fibrosis and necroinflammatory activity in the liver.

Hepatic artery thrombosis occurs when a blood clot forms in the artery that provides blood flow to the liver. Hepatic artery thrombosis may occur as a complication after liver transplantation, and represents the most common complication of liver transplantation. Smoking tobacco increases the risk of hepatic artery thrombosis in people who have undergone liver transplantation.

References

  1. 1 2 3 Giboney PT (March 2005). "Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient". Am Fam Physician. 71 (6): 1105–10. PMID   15791889.
  2. ↑ Maddrey, Willis C.; Schiff, Eugene R.; Sorrell, Michael F. (2007). Schiff's diseases of the liver. Hagerstwon, MD: Lippincott Williams & Wilkins. p. 924. ISBN   978-0-7817-6040-9.
  3. ↑ "Transaminasemia: semantic confusion of a clinical dilemma". Calif Med. 114 (6): 45–7. June 1971. PMC   1501958 . PMID   5578107.
  4. ↑ Ceriotti, F.; et al. (2010). "Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and g-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study". Clin Chem Lab Med. 48 (11): 1593–2101. doi:10.1515/CCLM.2010.315. PMID   21034260. S2CID   21929466.
  5. 1 2 Pettersson, J.; et al. (2007). "Muscular exercise can cause highly pathological liver function tests in healthy men". British Journal of Clinical Pharmacology. 65 (2): 253–259. doi:10.1111/j.1365-2125.2007.03001.x. PMC   2291230 . PMID   17764474.
  6. ↑ Hall, Philip; Cash, Johnny (January 2012). "What is the Real Function of the Liver 'Function' Tests?". The Ulster Medical Journal. 81 (1): 30–36. ISSN   0041-6193. PMC   3609680 . PMID   23536736.
  7. ↑ Lominadze, Zurabi; Kallwitz, Eric R. (October 2018). "Misconception: You Can't Have Liver Disease With Normal Liver Chemistries". Clinical Liver Disease. 12 (4): 96–99. doi:10.1002/cld.742. PMC   6385914 . PMID   30988921.
  8. ↑ Oh, RC; Hustead, TR (1 November 2011). "Causes and evaluation of mildly elevated liver transaminase levels". American Family Physician. 84 (9): 1003–8. PMID   22046940.
  9. ↑ Kwo, Paul Y.; Cohen, Stanley M.; Lim, Joseph K. (2017). "ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries" (PDF). Am. J. Gastroenterol. 112 (1): 18–35. doi:10.1038/ajg.2016.517. PMID   27995906. S2CID   23788795.
  10. ↑ Giboney, Paul T. (2005-03-15). "Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient". American Family Physician. 71 (6): 1105–1110. ISSN   0002-838X. PMID   15791889.
  11. ↑ Gitlin, N.; Serio, K. M. (Jul 1992). "Ischemic hepatitis: widening horizons". Am J Gastroenterol. 87 (7): 831–6. PMID   1615936.
  12. ↑ Fuchs, S.; Bogomolski-Yahalom, V.; Paltiel, O.; Ackerman, Z. (Apr 1998). "Ischemic hepatitis: clinical and laboratory observations of 34 patients". J Clin Gastroenterol. 26 (3): 183–6. doi:10.1097/00004836-199804000-00007. PMID   9600366.
  13. ↑ Henrion, J.; Schapira, M.; Luwaert, R.; Colin, L.; Delannoy, A.; Heller, F. R. (Nov 2003). "Hypoxic hepatitis: clinical and hemodynamic study in 142 consecutive cases". Medicine (Baltimore). 82 (6): 392–406. doi: 10.1097/01.md.0000101573.54295.bd . PMID   14663289. S2CID   27754941.
  14. ↑ Lok AS, McMahon BJ (February 2007). "Chronic hepatitis B". Hepatology. 45 (2): 507–39. doi:10.1002/hep.21513. hdl: 2027.42/55941 . PMID   17256718. S2CID   8713169.
  15. ↑ Raurich JM, Pérez O, Llompart-Pou JA, Ibáñez J, Ayestarán I, Pérez-Bárcena J (July 2009). "Incidence and outcome of ischemic hepatitis complicating septic shock". Hepatology Research. 39 (7): 700–5. doi:10.1111/j.1872-034X.2009.00501.x. PMID   19473435. S2CID   20312771.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.