Elevated transaminases

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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] transaminitis, 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

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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 commonly measured clinically as biomarkers for liver health. The tests are part of blood panels.

<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 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. Severe cases may be treated with glucocorticoids. The condition often comes on suddenly and may progress in severity very rapidly.

<span class="mw-page-title-main">Autoimmune hepatitis</span> Chronic, autoimmune disease of the liver

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<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

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<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.

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<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

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

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