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Alanine aminotransferase (ALT) is an enzyme found predominantly in the liver but also in other tissues such as the kidneys, heart, and muscle cells. An increase in ALT serum levels indicates definite liver cell injury due to many causes. An ALT blood test is often included in a liver panel and comprehensive metabolic panel to assess for damage to the liver. The liver has a central and critical biochemical role in the metabolism, digestion, detoxification, and elimination of substances from the body.[1] All blood from the intestinal tract initially passes through the liver, where products derived from the digestion of food are processed, transformed, and stored.[2] These include amino acids, carbohydrates, fatty acids, cholesterol, lipids, vitamins, and minerals. Most major plasma proteins (except immunoglobulins and the von Willebrand factor) are mainly or exclusively synthesized in the liver. The liver responds to multiple hormonal and neural stimuli to regulate blood glucose concentrations.[3] Not only does the organ extract glucose from the blood to generate energy, but it also stores dietary glucose as glycogen for later use. The liver is also the major site for gluconeogenesis, which is critical for maintaining blood glucose concentration in the fasting state.[4] The liver is central in lipid metabolism; it extracts and processes dietary lipids and is the principal site of cholesterol, triglyceride, and lipoprotein synthesis.[5] Another major liver function is the synthesis of bile acids from cholesterol, with the secretion of these compounds into the bile, which facilitates the absorption of dietary fat and fat-soluble vitamins.[6] The liver is also the primary site of metabolism of both endogenous substances and exogenous compounds (eg, drugs and toxins). This process, known as biotransformation, converts lipophilic substances to hydrophilic ones for subsequent elimination.[5] The liver is a major site of hormone catabolism and regulates plasma hormone concentrations.[6] The liver is also involved in hormone synthesis, producing the hormones insulin-like growth factor 1 (IGF-1), angiotensinogen, hepcidin, thrombopoietin, erythropoietin, and the prohormone 25-OH vitamin D. Many of these hepatic functions can be assessed by laboratory procedures to gain insight into the integrity of the liver.[1]

The liver is also the primary site of metabolism of both endogenous substances and exogenous compounds (eg, drugs and toxins). This process, known as biotransformation, converts lipophilic substances to hydrophilic ones for subsequent elimination.[5] The liver is a major site of hormone catabolism and regulates plasma hormone concentrations.[6] The liver is also involved in hormone synthesis, producing the hormones insulin-like growth factor 1 (IGF-1), angiotensinogen, hepcidin, thrombopoietin, erythropoietin, and the prohormone 25-OH vitamin D. Many of these hepatic functions can be assessed by laboratory procedures to gain insight into the integrity of the liver.[1] As a large organ, the liver has extensive reserve capacity to perform its functions in coordination with other organs. Individuals with liver disease maintain normal function despite extensive liver damage. In such cases, liver disease may be recognized only using tests that detect injury.[2] Most commonly, this is accomplished by measuring the plasma activities of enzymes found within liver cells, which are released in specific patterns with different forms of injury.[7] Chronic liver injury involves fibrosis in the liver. Markers of the fibrotic process might indicate the degree of injury.[8] Chronic damage is often due to chronic inflammation. Cytokines can alter the liver's protein production pattern, making it possible to detect inflammation, not necessarily related to the liver.[9] Some proteins are produced in increased amounts with liver regeneration and neoplasia; the markers may be useful in detecting liver cell proliferation.[10] This review focuses on the significance of ALT in assessing hepatic injury and malfunction. ALT is aggregated primarily in the cytosol of hepatocytes, consists of 496 amino acids, and has a half-life of approximately 47 hours.[11] ALT is detectable in serum at low concentrations (typically <30 IU/L). However, any process that leads to loss of hepatocyte membrane integrity or necrosis results in the release of ALT in high concentrations in the plasma.[2]

This review focuses on the significance of ALT in assessing hepatic injury and malfunction. ALT is aggregated primarily in the cytosol of hepatocytes, consists of 496 amino acids, and has a half-life of approximately 47 hours.[11] ALT is detectable in serum at low concentrations (typically <30 IU/L). However, any process that leads to loss of hepatocyte membrane integrity or necrosis results in the release of ALT in high concentrations in the plasma.[2] Therefore, the elevation of serum ALT concentration is sensitive but not specific to measure hepatocellular injury, as the degree of elevation cannot determine the exact cause.[1] The most common causes are alcohol-induced liver injury, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B or C, autoimmune hepatitis, and drug or herbal supplement-induced liver injury.[4] Other causes include hemochromatosis, vascular disease, acute viral hepatitis, and genetic disorders affecting the liver.[7]

ALT catalyzes the transfer of amino groups from the L-alanine to alpha-ketoglutarate, and the conversion products are L-glutamate and pyruvate. The process is critical in the liver in the tricarboxylic acid (TCA) cycle. Pyruvate can be used in the citric acid cycle to produce cellular energy. The coenzyme needed for this reaction is pyridoxal 5'-phosphate, also known as vitamin B6.[27] The pyridoxal 5'-phosphate (P-5′-P) is bound to the inactive apoenzyme and is a true prosthetic group. The pyridoxal 5'-phosphate attached to the apoenzyme accepts the amino group from the first substrate, aspartate or alanine, to form enzyme-bound pyridoxamine-5′-phosphate and the first reaction product, oxaloacetate or pyruvate, respectively.[28] The coenzyme in the amino form then transfers its amino group to the second substrate, 2-oxoglutarate, to form the second product, glutamate. The pyridoxal 5'-phosphate (P-5′-P) is regenerated.[29] Both coenzyme-deficient apoenzymes and holoenzymes may be present in serum.[30] Therefore, adding P-5′-P under measurement conditions that facilitate recombination with the enzymes usually increases aminotransferase activity. For clinical assays, following the principle that all factors affecting the reaction rate must be optimized and controlled, adding P-5′-P in aminotransferase methods is recommended to ensure that all enzymatic activity is measured.[31] ALT is found ubiquitously throughout the human body, in the kidney, myocardium, skeletal muscle, brain, pancreas, spleen, and lungs. More specifically, the highest tissue concentration of ALT activity is in the cytosol of hepatocytes. The activity of ALT in hepatocytes is approximately 3000 times higher than that of serum ALT activity.[32] Therefore, in patients with acute or chronic hepatocellular injury, the release of ALT from dying or damaged hepatocytes increases serum ALT levels. The half-life of ALT is approximately 47 hours in circulation.[33]

Multi-disciplinary and interprofessional rounds are when medical and other health providers collaborate to enhance patient outcomes. Clinicians may review the significance of the hepatic function test panel in correlation with each patient's medical history and physical examination to detect any drug-induced hepatic injury and build a differential diagnosis. Changes in the patient's patterns of ALT and AST over time or other liver function tests may necessitate a referral to gastroenterologists. Clinical pharmacists can also advise about potential contraindications or hepatotoxic medication interactions. The charge nurse of each floor can communicate updates on a patient's response to treatment, other laboratory orders, and current disposition. A multi-disciplinary approach can ensure a higher quality of care and enhance outcomes.[90]