Moriles Kevin E., Zubair Muhammad, Azer Samy A.
Advent Health South
Pakistan Kidney & Liver Institute and Research Centre - PKLI
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. All blood from the intestinal tract initially passes through the liver, where products derived from the digestion of food are processed, transformed, and stored. 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. 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. The liver is central in lipid metabolism; it extracts and processes dietary lipids and is the principal site of cholesterol, triglyceride, and lipoprotein synthesis. 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. 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. The liver is a major site of hormone catabolism and regulates plasma hormone concentrations. 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. 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. 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. Chronic liver injury involves fibrosis in the liver. Markers of the fibrotic process might indicate the degree of injury. 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. Some proteins are produced in increased amounts with liver regeneration and neoplasia; the markers may be useful in detecting liver cell proliferation. 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. 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. 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. 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. Other causes include hemochromatosis, vascular disease, acute viral hepatitis, and genetic disorders affecting the liver.
丙氨酸转氨酶（ALT）是一种主要存在于肝脏中的酶，但在其他组织如肾脏、心脏和肌肉细胞中也有发现。血清ALT水平升高表明由于多种原因导致肝细胞损伤。ALT血液检测通常包含在肝功能检查和综合代谢检查中，以评估肝脏是否受损。肝脏在人体物质的代谢、消化、解毒和排泄过程中起着核心且关键的生化作用。所有来自肠道的血液最初都会流经肝脏，在这里，食物消化产生的产物会被加工、转化和储存。这些物质包括氨基酸、碳水化合物、脂肪酸、胆固醇、脂质、维生素和矿物质。大多数主要的血浆蛋白（免疫球蛋白和血管性血友病因子除外）主要或仅在肝脏中合成。肝脏通过对多种激素和神经刺激做出反应来调节血糖浓度。该器官不仅从血液中提取葡萄糖以产生能量，还将膳食中的葡萄糖储存为糖原以供后续使用。肝脏也是糖异生的主要场所，这对于维持空腹状态下的血糖浓度至关重要。肝脏在脂质代谢中起核心作用；它提取并处理膳食脂质，是胆固醇、甘油三酯和脂蛋白合成的主要场所。肝脏的另一项主要功能是由胆固醇合成胆汁酸，并将这些化合物分泌到胆汁中，这有助于膳食脂肪和脂溶性维生素的吸收。肝脏也是内源性物质和外源性化合物（如药物和毒素）代谢的主要场所。这个过程称为生物转化，它将亲脂性物质转化为亲水性物质以便随后排出体外。肝脏是激素分解代谢的主要场所，并调节血浆激素浓度。肝脏还参与激素合成，产生胰岛素样生长因子1（IGF - 1）、血管紧张素原、铁调素、血小板生成素、促红细胞生成素以及激素原25 - 羟基维生素D。许多这些肝脏功能可以通过实验室检查来评估，以深入了解肝脏的完整性。作为一个大器官，肝脏具有广泛的储备能力，可与其他器官协同执行其功能。患有肝病的个体尽管肝脏有广泛损伤，但仍能维持正常功能。在这种情况下，可能只有通过检测损伤的检查才能识别肝病。最常见的方法是测量肝细胞内发现的酶的血浆活性，这些酶会以特定模式随着不同形式的损伤而释放。慢性肝损伤会导致肝脏纤维化。纤维化过程的标志物可能表明损伤程度。慢性损伤通常是由慢性炎症引起的。细胞因子可以改变肝脏的蛋白质产生模式，从而有可能检测到不一定与肝脏相关的炎症。一些蛋白质在肝脏再生和肿瘤形成时产生量会增加；这些标志物可能有助于检测肝细胞增殖。本综述重点关注ALT在评估肝损伤和肝功能障碍中的意义。ALT主要聚集在肝细胞的胞质溶胶中，由496个氨基酸组成，半衰期约为47小时。在血清中可以检测到低浓度的ALT（通常<30 IU/L）。然而，任何导致肝细胞膜完整性丧失或坏死的过程都会导致血浆中高浓度的ALT释放。因此，血清ALT浓度升高对测量肝细胞损伤很敏感，但不具有特异性，因为升高程度无法确定确切病因。最常见的病因是酒精性肝损伤、非酒精性脂肪性肝病（NAFLD）、非酒精性脂肪性肝炎（NASH）、慢性乙型或丙型肝炎、自身免疫性肝炎以及药物或草药补充剂引起的肝损伤。其他病因包括血色素沉着症、血管疾病、急性病毒性肝炎以及影响肝脏的遗传性疾病。
