What Causes AST and ALT Levels To Be High?

The liver is the largest organ of the human body and one of the most important in terms of metabolic activity that develops in the organism.

Its innumerable functions include: 1) Glycogen storage; 2) Synthesis of fatty acids and conversion to ketones, formation of lipoproteins, cholesterol and phospholipids; 3) Plasma protein synthesis, amino acid conversion and deamination and urea formation; 4) Metabolism and vitamin store; 5) Synthesis, release and degradation of coagulation factors; 6) Catabolism and hormone excretion; 7) Detoxification of endogenous substances (Bilirubin), bacteria, byproducts and exogenous items (drugs); 8) Bile formation: secretory and excretory; 9) Maintenance of the electrolytic balance and 10) Defensive barrier by half of cells of the Endothelial Reticular System.

In daily clinical practice, the multiple liver functions are only overcome by the biochemicals methods designed to examine them.

Schematically, hepatic functional tests can be divided into: a) Tests that report possible hepatocellular injury or cytolysis; b) Tests related to the metabolism of bilirubin (uptake, conjugation and excretion), as well as bile deficit (cholestasis); and c) Tests that analyze the hepatic synthesis of categories necessary for body functionalism. Usually many of these functions are altered at the same time, although there are isolated forms with singular affectation.

Among the tests that report hepatocellular injury or cytolysis for transaminases or aminotransferases. These represent enzymes of the intermediate metabolism, which catalyze the transfer of amino groups from aspartic acid or alanine to acetoglutaric acid, forming oxalacetic acid and pyruvic acid. Multiple transamination reactions occur in the liver, but the only transaminases with clinical value are two:

1. Aspartate aminotransferase or glutamic-oxalacetic transaminase (AST or GOT) whose half-life is 48 hours.
2. Alanine aminotransferase or glutamic-pyruvic transaminase (ALT or GPT) with a half-life of 18 hours. ALT is more specific for liver damage than AST, because the first is located almost exclusively in the cytosol of the hepatocyte, while the AST, in addition to the cytosol and mitochondria, is found in the heart, skeletal muscle, kidneys, brain, pancreas, lung, erythrocytes and leukocytes.

The serum elevation of transaminases is correlated with the discharge to the blood of the enzymatic content of the affected hepatocytes, although the gradation of enzymatic elevation may not be related to lesional severity.

Thus, liver disease can be considered as the most important cause of the increase in ALT activity and frequent increase of the activity of the AST.

Both enzymes (ALT and AST) are normally present in low concentrations in serum, with values lower than 40 U/l, although the range of normality varies according to laboratories. The distribution of normality values does not show a typical distribution.

Thus, values higher than the 97th percentile are considered pathological.

-An elevation of transaminases less than twice the high limit of the normal range should be confirmed with another determination before the start of any other complementary study, since there are factors that can modify the enzymatic activity without there being liver injury. These factors are: Moment of the day of the extraction, variation between days, race/sex, body mass index, meals, exercise, hemolysis, hemolytic anemias, muscular damage and storage conditions.

Once verified the real hypertransaminemia, it will be the interrogation and a detailed physical examination that orientate the doctor of signs/symptoms of hepatic affectation, although this enzymatic elevation can be the only manifestation of the hepatic injury.

First, viral serology is requested, as this is one of the most frequent causes of hepatitis. The major (A, B, C, D, E, G) and minor (CMV, EBV, herpes, adenovirus, paramyxovirus, parvovirus, etc) hepatotropic viruses will be valued. If the virological markers are negative, the next etiology to be ruled out will be the hepatic lesion due to toxic or drugs.

The AST / ALT ratio can guide us on a specific pathology according to the following scheme: AST / ALT ≤ 1: Viral hepatitis, AST / ALT> 2: Cirrhosis (of any etiology), AST / ALT> 4: Suggests acute liver failure.

When there´s increase in serum transaminases, a stepped request for complementary tests is necessary to achieve the appropriate diagnostic-therapeutic approach of the responsible entity.