Information

Are there known functions of AST, ALT, and amylase in the blood?


A number of enzymes can be measured in the blood or plasma that aid in the diagnosis of certain diseases. For example, patients with particular liver diseases may have elevated aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) levels in the blood. These enzymes are normally involved in biochemical reactions of metabolism that interconvert amino acids with other metabolic intermediates - that is, biochemical reactions that are common within the liver cell. Also, patients with pancreatitis frequently have elevated amylase and lipase levels, which are digestive enzymes normally secreted into the gastrointestinal tract. During pancreatitis these enzymes are released into the blood, rising and falling with the resolution of pancreatic damage/inflammation.

Pathologically, the tissues that are damaged in these diseases (liver and pancreas, respectively) are the source of the elevated enzymes. In healthy individuals, however, these same enzymes are still found in low concentrations in the circulating blood. What is the source of these enzymes that are found in low circulating concentrations? Is it still those same tissues (e.g. AST/ALT from the liver)? Is this secondary to "normal turnover" of cells within those tissues? Or, alternatively, are these enzymes secreted into the blood to serve a particular function?


For example… There is a freely available manuscript by Arnold and Rutter published in the Journal of Biological Chemistry (1963) that discusses experimental evidence for active amylase secretion from the liver during an isolated liver perfusion experiment. Amylase continues to be secreted, even in the absence of other enzymes that would otherwise indicate liver damage (suggesting that the amylase is intentionally being secreted for some unknown purpose). This is an paper from almost 60 years ago - do we know what some of these enzymes like AST/ALT and amylase do in the plasma? Or are those functions still unknown?


These enzymes, while useful markers of disease, are not only produced during the disease state, and are not only produced in one organ. It is therefore not surprising that there are always low levels released into the biochemical milieu that is the blood. If there are not even low levels of the enzymes then that might indicate that the organ is not doing it's job properly.

I'll approach this from a veterinary viewpoint but I imagine it is much the same in humans. My preferred source for information about veterinary clinical pathology is Cornell's EClinpath site.

The major tissue sources of AST are liver, skeletal muscle, and cardiac muscle. A small amount is produced by erythrocytes. In lesser concentrations it is also found in renal epithelial cells and brain tissue. It therefore should be no surprise that low levels are found in blood. It is not difficult to picture a small amount of leakage from erythrocytes in the normal state, even without pathologic haemolysis, given the regular turnover of cells and permeability of erythrocytes - although I suspect this is a minor source. Just due to the fact that the liver's normal function is to deal with many cytotoxic compounds, even in the completely healthy patient there always is going to be some low level of hepatocellular damage. As a result, a very low serum level of AST might be indicative of a poorly functioning liver (e.g. with a chronic hepatitis).

Among veterinary species there is considerable variation in the clinical usefulness of ALT. For example, it is a very useful indicator of liver disease in dogs and cats, much less so in horses. Much like AST, ALT is also produced in liver, muscle, kidney, and erythrocytes.

Amylase is known to be produced by cells in the pancreas, salivary gland, duodenum, ileum, ovary, and testes. Of course, the pancreas produces the most of this enzyme, which is why it is somewhat clinically useful (though I can't say I like it much at least for veterinary species).

The bottom line is that these enzymes play an important role in biochemical reactions of many different tissues. While the enzymes may be produced in predominance in one tissue, they have the same function (at a biochemical level) in all these tissues (i.e. they convert the same reactions). I view it more as a difference of the tissue need for these enzymes rather than a difference in function between tissues.


What are liver enzymes?

They’re proteins that help speed up a chemical reaction in the liver. Blood tests, called liver function tests, are used to evaluate various functions in the liver. Examples of these functions are metabolism, filtration and excretion and storage, which are often performed by liver enzymes. But not all liver function tests measure enzyme function.

Liver enzymes are found in normal plasma and serum and can be divided into different groups.

  1. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT). Together these enzymes are known as transaminases.
  2. Alkaline phosphatase (AP) and gammaglutamyl transferase (GGT) are known as cholestatic liver enzymes. If these enzymes are elevated it can indicate the presence of liver disease.
  3. Secretory enzymes are enzymes made in the liver and allocated to the blood plasma. Their role is physiological, for example, enzymes involved in blood clotting (AC globulin) or cholinesterase, which catalyzes the hydrolysis of acetylcholine. Damage to the liver will reduce their synthesis leading to a decrease in their enzyme activity.

AST and ALT

There are enzymes that enter into the blood from the tissues to perform intracellular functions. Some of the enzymes are in the cell cytosol, such as ALT, AST and LDH, and others are in the cell mitochondria, such as GGT and AP. Any damage to the liver will cause the enzymes from the cells to enter the blood and their activity will increase. Amounts of ALT and AST are the greatest diagnostic value. In parenchymatous hepatitis serum transaminase ALT increases, sometimes 100 times or more and AST to a lesser extent. In addition to the liver, AST enzymes can be found in the heart, muscle, brain and kidney and is released into blood serum when these tissues become damaged. For example, a heart attack or muscle disorders will increase AST serum levels. Because of this AST isn’t necessarily an indicator of liver damage.ALT is almost specifically found in the liver. After liver injury it’s released into the bloodstream and therefore can be used as a fairly specific indicator of liver function.

It’s common for high levels of AST and ALT in the liver to damage numerous liver cells, called hepatic necrosis and can lead to death of the cells. The higher the ALT levels the greater the amount of cell death. Despite this ALT’s aren’t always a good indicator of how well the liver is functioning. Only a liver biopsy can reveal this. Diseases that can cause increased levels of liver enzymes AST and ALT are acute viral hepatitis A or B, as well as toxins caused by acetaminophen overdose,or a prolonged collapse of the circulatory system, which is called shock. It deprives the liver of fresh blood that brings oxygen and nutrients. Transaminase levels can be 10 times the upper limit.

Sometimes elevated liver enzymes can be found in otherwise healthy individuals. In such cases they’re usually found to be twice the upper limit. Fatty liver is a common problem causing elevated liver enzymes. In the United States and other countries in the world the most frequent causes of fatty liver are alcohol and drug abuse, obesity, diabetes, and sometimes chronic hepatitis C.

Alkaline Phosphatase

Alkaline phosphatase is an enzyme that’s produced in the bile ducts, kidney, intestines, placenta and the bone. If this enzyme is high and ALT and AST levels are pretty normal there could be a problem with the bile duct such as an obstruction. Some bone disorders may also cause alkaline phosphatase levels to increase. If there is an elevation of alkaline phosphatase it could also indicate there is an injury to the biliary cells. This could be due to gallstones or certain medications. Under normal circumstances the enzyme is mainly allocated to the bile, but if pathology exists the norm is disturbed and the enzyme increases in blood plasma.

Gamma-Glutamyltranspeptidase

GGT is another enzyme that’s produced in the bile ducts and can become elevated if there is a problem with the bile ducts. High levels of GGT and AP indicate a possible blockage of the bile ducts or a possible injury or inflammation of the bile ducts. This problem is characterized by an impairment or failure of bile flow and is known as cholestasis and the term refers to bile duct blockage or injury within the liver. As a rule, intrahepatic cholestasis will occur in individuals with primary biliary cirrhosis or liver cancer. The term extrahepatic cholestasis refers to bile duct blockage or injury outside of the liver and may occur in individuals with gallstones.GGT and AP can seep out of the liver and into the bloodstream, but only with blockage or inflammation of the bile ducts. The enzymes will be about ten times the upper normal limit.Unlike AP, GGT is found predominantly in the liver. Taking this into account, GGT is a sensitive marker of alcohol ingestion and certain hepatotoxic (liver toxic) drugs, where is can be elevated without AP elevation. It’s unclear why, but cigarette smokers have a higher GGT and AP levels than nonsmokers. When testing levels of AP and GGT the levels will be most accurate after a 12 hour fast.

Nonalcoholic Fatty Liver

Normal levels of alkaline phosphatase range from 35 to 115 IU/Liter and the normal levels of GGT range from 3 to 60 IU/Liter. Causes of elevated AP and GGT are:

  • Alcoholic liver disease
  • Primary biliary cirrhosis
  • Liver tumors
  • Nonalcoholic fatty liver disease
  • Gallstones
  • Primary sclerosing cholangitis
  • Drugs that are used to treat liver disease

Liver Tumor

One study at the Mayo Clinic was conducted over ten years and determined that an excess of enzymes in the liver is associated with the risk of death. High levels of aspartate aminotransferase and alanine aminotransferase in the blood not only can develop into liver disease, but can also have a fatal outcome.

Stages of Liver Damage

A group of enzymes, that are located in the endoplasmic reticulum, known as cytochrome P-450, is the most important family of metabolizing enzymes found in the liver. Cytochrome P-450 is the terminal oxidase component of an electron transport chain. It’s not a single enzyme, but consists of a family of closely related 50 isoforms. Six of them metabolize 90% of drugs. There is a great diversity of individual P-450 gene products and this heterogeneity allows the liver to perform oxidation on a vast array of chemicals, which includes almost all drugs.

Hepatotoxic Drugs

  • isoniazid
  • phenytoin
  • aspirin
  • acetaminophen
  • methyldopa
  • diclofenac
  • allopurinol
  • oral contraceptives
  • carbamazepine
  • ketoprofen
  • tetracycline
  • methotrexate
  • anabolic steroids
  • androgens
  • chlorpromazine
  • penicillin
  • quinine
  • amiodarone
  • chemotherapeutic drugs

Acetaminophen overdose is the most common cause of drug induced liver disease


Understanding the ALT AST Blood Test Results

The ALT AST blood test combination is often ordered to gain a glimpse into a patient’s liver health. Not only are they considered to be the two most important tests to discover the presence of a liver injury, but they can also be used to determine certain organ disorders.

These two blood tests are often used in conjunction with the ALP blood test, with results compared, to determine the total extent of liver health.

When to Ask a Doctor About the ALT AST Blood Test Combination

These two blood tests are often ordered when a patient is reporting the signs and symptoms of a possible liver disorder. Common symptoms may include weakness, fatigue, a loss of appetite, nausea, vomiting, and swelling of the abdomen which may or may not be painful.

Liver-specific symptoms may also be present. This may include a yellowing of the skin, dark urine, light-colored stools, and frequent itching.

These blood tests may also be ordered on a regular basis for individuals who have an increased risk of suffering liver damage, but may not be experiencing any of the bothersome symptoms listed above. Examples of this include hepatitis viral exposure, a history of alcoholism or heavy drinking, a family history of liver disease, being obese, or having diabetes.

Certain medications can affect ALT and AST levels as well and may require ongoing monitoring to determine the health of the liver.

What Do My Test Results Mean?

The normal range for the ALT blood test is usually reported between 5-55 units per liter. The AST blood test has a normal range of 10-40 units per liter. Every laboratory has its own normal range, however, so certain results that fall outside of these reported norms may still be considered a “normal” result by some medical providers.

In general terms, the amount of elevation that is seen above this normal range is treated as an indication of the severity of infection or injury that is affecting the liver. This means a test result that is 20 times higher than the maximum normal result would indicate more severity in the injury to the organ than a test result which is just 5 times higher.

Elevated readings from these blood tests are often the result of an acute viral hepatitis infection. This includes Hepatitis A and B. Chronic viral hepatitis can also produce elevated results. Liver cirrhosis also elevates ALT and AST levels, as does organ damage from alcohol, or a diminished flow of blood from the heart to the liver for some reason.

Lower than normal test results for ALT and AST are generally treated as a “normal” result. A healthy liver produces very little ALT and AST. There may be co-related conditions which are affecting the blood test results which need to be examined to determine the lower-than-normal results experienced.

Here’s What You Need to Know

Certain low-level rises in ALT and AST can also be seen with certain lifestyle choices, including strenuous workouts, shots, or injections. Anything that strains the muscles may increase ALT levels. AST levels naturally rise after a surgery, receiving an acute burn, or during a pregnancy. Individuals with frequent seizures will typically have higher than normal AST levels present on a regular basis.

Prescription drugs aren’t the only cause of rising ALT and AST levels either. Some natural health products have also been known to influence blood test results. Patients taking vitamins and herbal supplements will wish to tell their healthcare provider about everything they are taking on a regular basis.

And although this blood test combination is generally associated with liver health, there are other conditions that may cause elevations of ALT and AST. Anything that affects the heart or skeletal muscles will also elevate test results above normal ranges. Some increases are also seen with acute health issues associated with the pancreas.

Depending on what is suspected to cause the liver damage, follow-up tests may be required after this panel. This may include testing for copper, ethanol, iron, drug abuse, and hepatitis infection. Certain medications may be altered to determine if they are causing side effects which could be damaging the liver.

The ALT AST blood test combination is used to determine the extent of liver damage and overall health. Only a medical provider can determine what a test result means for each individual. Use this guide to discuss your current health concerns during your next appointment to determine if these blood tests may be right for you.


Evaluation Based on Enzyme Levels

It is customary and useful to categorize liver diseases into three broad categories: Hepatocellular, in which primary injury is to the hepatocytes cholestatic, in which primary injury is to the bile ducts and infiltrative, in which the liver is invaded or replaced by non-hepatic substances, such as neoplasm or amyloid. Although there is a great deal of overlap in liver test result abnormalities seen in these three categories, particularly in cholestatic and infiltrative disorders, an attempt to characterize an otherwise undifferentiated clinical case as hepatocellular, cholestatic, or infiltrative often makes subsequent evaluation faster and more efficient. The AST, ALT, and alkaline phosphatase tests are most useful to make the distinction between hepatocellular and cholestatic disease.

The normal range for aminotransferase levels in most clinical laboratories is much lower than that for the alkaline phosphatase level. Accordingly, when considering levels of elevations, it is necessary to consider them relative to the respective upper limit of normal for each test compared. Consider a patient with an AST level of 120 IU/mL (normal, &le40 IU/mL) and an alkaline phosphatase of 130 IU/mL (normal, &le120 IU/mL). This represents a hepatocellular pattern of liver injury because the AST level is three times the upper limit of normal, whereas the alkaline phosphatase level is only marginally higher than its upper limit of normal.

Serum aminotransferase levels&mdashALT and AST&mdashare two of the most useful measures of liver cell injury, although the AST is less liver specific than is ALT level. Elevations of the AST level may also be seen in acute injury to cardiac or skeletal muscle. Lesser degrees of ALT level elevation may occasionally be seen in skeletal muscle injury or even after vigorous exercise. Thus in clinical practice, it is not uncommon to see elevations of AST, ALT or both in common non-hepatic conditions such as myocardial infarction and rhabdomyolysis. Diseases that primarily affect hepatocytes, such as viral hepatitis, will cause disproportionate elevations of the AST and ALT levels compared with the alkaline phosphatase level. The ratio of AST/ALT is of little benefit in sorting out the cause of liver injury except in acute alcoholic hepatitis, in which the ratio is usually greater than 2.

The current upper limit of serum ALT, though varied among laboratories, is generally around 40 IU/L. However, recent studies have shown that the upper limit threshold of ALT level should be lowered because people who have slightly raised ALT levels that are within the upper limit of normal (35-40 IU/L) are at an increased risk of mortality from liver disease. In addition, it has been suggested that gender-specific thresholds be applied because women have slightly lower normal ALT levels than men. One such study conducted in the U.S. identified an ALT upper limit of 29 IU/L for men and 22 IU/L for women. In asymptomatic patients with minimal elevations of aminotransferases, it is reasonable to repeat the test in a few weeks to confirm elevation. Common causes of mild increases in AST and ALT levels include non-alcoholic fatty liver disease (NAFLD), hepatitis C, alcoholic fatty liver disease, and medication effect (e.g., due to statins).

Serum alkaline phosphatase comprises a heterogeneous group of enzymes. Hepatic alkaline phosphatase is most densely represented near the canalicular membrane of the hepatocyte. Accordingly, diseases that predominately affect hepatocyte secretion (e.g., obstructive diseases) will be accompanied by elevations of alkaline phosphatase levels. Bile-duct obstruction, primary sclerosing cholangitis, and primary biliary cirrhosis (PBC) are some examples of diseases in which elevated alkaline phosphatase levels are often predominant over transaminase level elevations (Table 2).

Table 2: Category of Liver Disease by Predominant Serum Enzyme Abnormality


Liver Disease Category
Test Hepatocellular Cholestatic Infiltrative
AST, ALT higher than alkaline phosphatase level Typical &mdash &mdash
Alkaline phosphatase higher than AST, ALT levels &mdash Typical &mdash
Elevation of alkaline phosphatase with near-normal AST, ALT levels &mdash Typical Typical

ALT, alanine aminotransaminase AST, aspartate transaminase.

Infiltrative liver diseases most often result in a pattern of liver test result abnormalities similar to those of cholestatic liver disease. Differentiation often requires liver imaging studies. Liver imaging by ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) most often identify infiltration of the liver by mass lesions such as tumors. Imaging by cholangiography&mdashendoscopic retrograde cholangiography, transhepatic cholangiography, or magnetic resonance cholangiography&mdashidentifies many bile duct lesions that cause cholestatic liver disease. Liver biopsy is often needed to confirm certain infiltrative disorders (e.g., amyloidosis) and microscopic biliary disorders such as PBC.

Bilirubin Level Elevations

Bilirubin is produced by the normal breakdown of pigment-containing proteins, especially hemoglobin from senescent red blood cells and myoglobin from muscle breakdown. Bilirubin released from such sources, tightly albumin bound, is delivered to the liver, where it is efficiently extracted and conjugated by hepatic glucuronidation and sulfation. Conjugated bilirubin is rapidly excreted into bile and removed from the body through the gut. Therefore, the amount of conjugated bilirubin present in serum in healthy subjects is trivial (<10% of measured total bilirubin). An elevated level of conjugated serum bilirubin implies liver disease. Also, it is important to note that only conjugated bilirubin appears in urine (unconjugated bilirubin is albumin bound and water insoluble). The presence of bilirubin in urine almost always implies liver disease.

Many laboratories report only the total bilirubin level, the sum of the conjugated and unconjugated portions. It is sometimes useful to determine the fraction of total serum bilirubin that is unconjugated versus that which is conjugated, usually referred to as fractionation of bilirubin. This is most useful when all the standard liver test results are normal, except the total bilirubin. To make matters more confusing, the conjugated bilirubin is sometimes referred to as the direct-reacting bilirubin and the unconjugated as the indirect-reacting bilirubin (Table 3).

Table 3: Bilirubin Fractions Present in Blood and Urine

Fraction In Serum As Measured As Present in Urine
Unconjugated Albumin-bound Indirect-reacting bilirubin Never
Conjugated Unbound Direct-reacting bilirubin Yes, when serum bilirubin level is elevated

Normally, 90% or more of measured serum bilirubin is unconjugated (indirect-reacting). When the total bilirubin level is elevated and fractionation shows that the major portion (&ge90%) is unconjugated, liver disease is never the explanation. Instead, the clinician should suspect one of two explanations: Gilbert disease or hemolysis. If the patient is young and healthy, an inherited decrease in the inability to conjugate bilirubin is likely and is referred to as Gilbert syndrome. It is seen in about 5% of the general population and causes only mild hyperbilirubinemia without symptoms. It is not associated with liver disease. Interestingly, fasting and intercurrent illnesses such as influenza often make the level of unconjugated bilirubin even higher in those with Gilbert syndrome. This syndrome is easily diagnosed when all standard liver-test results are normal and 90% or more of the total bilirubin is unconjugated. There is no need for an imaging study or liver biopsy in cases of suspected Gilbert syndrome.

Elevations of the unconjugated bilirubin level when the conjugated bilirubin level remains normal may also indicate an increased load of bilirubin caused by hemolysis. Anemia and an elevated reticulocyte count are usually present in such cases (Table 4).

Table 4: Common Causes of Isolated Bilirubin Elevation

Cause Direct-Reacting Bilirubin Indirect-Reacting Bilirubin Associated Features
Liver disease (many types) Elevated Elevated or normal Liver enzyme levels often elevated
Hemolysis Normal Elevation represents more than 90% of total bilirubin Anemia usual increased reticulocyte count normal liver enzyme levels (although LDH may be elevated)
Gilbert's syndrome Normal Elevation represents more than 90% of total bilirubin (common) No abnormal liver tests no anemia onset in late adolescence fasting makes bilirubin rise

LDH, lactate dehydrogenase.

Many clinicians mistakenly interpret elevations of direct-reacting bilirubin to indicate that cholestatic (obstructive) liver disease is present. It is apparent from Table 2 that the serum bilirubin level plays no useful role in categorizing a case as hepatocellular, cholestatic, or infiltrative. The bilirubin level may be normal or elevated in each type of disorder. Viral hepatitis A, a prototypic hepatocellular disease, may frequently be associated with bilirubin levels that are high, whereas PBC, a prototypic cholestatic disorder, is associated with a normal serum bilirubin level except in later stage disease. Serum bilirubin levels should be disregarded when trying to decide whether the liver-test pattern is more suggestive of hepatocellular or cholestatic disease.


What Does it Mean if a Dog has Elevated Liver Values?

By Mara Ratnofsky, DVM
angell.org/generalmedicine
617-522-7282

The liver is an amazing organ which carries out over 500 life-sustaining functions. It processes all of the blood leaving the gastrointestinal tract – breaking down toxins, converting medications into forms that can be better used by the body, and creating nutrients. The liver stores energy and iron for future use by the body, helps regulate blood clotting, and clears old red blood cells from circulation. The liver secretes its waste products in the form of bile, a substance which also aids in the digestion of fats.

Your veterinarian may recommend a blood test to check your dog’s liver values. This may be part of a routine screen to get a more complete picture of your dog’s overall health, or your vet may have concerns about your dog’s liver function. Poor appetite, vomiting, lethargy, increased drinking and urination, yellow discoloration of the eyes or skin, seizures, and fluid build-up in the abdomen can all be signs of liver disease.

Below is a breakdown of what your vet is evaluating when he or she looks at “liver values.”

1) Hepatocellular Enzymes – AST (aspartate aminotransferase) and ALT (alanine aminotransferase)

AST and ALT are enzymes contained within liver cells. When levels are increased in the blood, it means that the enzymes have leaked out of the liver cells due to cell damage. AST is found in muscle cells as well as liver cells, so an elevation in AST without a similar elevation in ALT may indicate muscle damage rather than liver damage. Although ALT elevations are specific for liver, there are many non-liver diseases that can indirectly affect the liver and cause increases in ALT. For example, heart failure and intestinal inflammation can cause an increase in ALT up to 4 or 5 times the normal range. Even severe dental disease can cause an elevation in ALT. In terms of primary liver issues, ingestion of certain toxins or chronic inflammation of the liver (due to infection, an over-reaction of the immune system, genetic disorders, etc.) tend to create the most significant ALT elevations.

2) Cholestatic Enzymes – ALP (alkaline phosphatase) and GGT (γ-glutamyl transpeptidase)

ALP and GGT are contained in the cells that line the bile ducts – thin tubes that guide the flow of bile from the liver to the small intestine. If bile flow is blocked, these cells increase production of ALP and GGT and release them into the blood. Causes of poor bile flow within the liver include nodular hyperplasia (a benign condition of older dogs), overwhelming infection, cancerous tumors, and blood vessel abnormalities. However, there are several different forms of ALP in the dog and our routine laboratory tests can’t differentiate between them. Dogs under a year old usually have an elevated ALP as a result of bone growth, as there is a form of ALP associated with bone (B-ALP). Dogs taking steroid medication often have an elevated ALP because there is a form stimulated by the presence of steroids (C-ALP). These elevations are not indicative of liver dysfunction. Certain dog breeds, such as Scottish terriers, Siberian huskies, and miniature Schnauzers, also tend to have benign elevations in ALP. And just as with the hepatocellular enzymes, the cholestatic enzymes will also increase due to the effect of non-liver diseases on the liver. Pancreatitis, gall bladder disease, intestinal inflammation, and certain endocrine diseases all increase ALP.

Other routine lab results can also help us identify liver disease. Since the liver is responsible for making albumin (a blood protein) and cholesterol, a low albumin or low cholesterol level might be the result of severe liver disease. Yellowing of the eyes and skin, also known as jaundice or icterus, can occur when the liver is not effectively removing broken-down old red blood cells from circulation. Low blood sugar can result when a diseased liver is not able to release its stored energy.

As you can see, an elevation in liver values doesn’t necessarily mean there is a serious problem with your dog’s liver. Your veterinarian will take into consideration your dog’s breed, age, medical history, as well as recent medications and additional lab results, to determine if there is a benign explanation for the lab results, if monitoring liver values for several months is appropriate, or if further diagnostics are warranted. Additional diagnostics might include x-rays, an abdominal ultrasound, more blood tests (bile acids, ammonia level), or liver biopsy. In any case, the liver has an amazing capacity to regenerate, so the presence of even significantly elevated liver values doesn’t necessarily mean a poor prognosis.


Diagnosis and Treatment of Elevated Liver Enzymes in Dogs

The vet will start by looking at your dogs previous medical history as this may give an indication as to whether your dig is showing the same symptoms. The diagnosis of raised liver enzymes will normally be achieved through X-rays, blood tests, liver biopsy and urinalysis.

Treatment may depend on how ill your dog is and how badly affected the liver is. Treatment may include a better diet that is low in protein and low in sodium levels. To support the liver and improve its health the vet may prescribe a medication called Denosyl or antibiotics.

Just as I was obtaining my Texas real estate license online, my dog started having this issue, and it was very stressful. I know how hard this is to deal with, so hopefully this articles helped.


How to Lower ALT and AST Liver Enzymes

High levels of liver enzymes in the blood stream are a prime indicator of liver disease. Low levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) in the blood are normal, but high levels require action. More ALT and AST enzymes are able to enter the blood if the liver’s membrane is deteriorating. This situation is not a time for panic, but it does indicate a problem, which requires changes to your lifestyle.

Test for hepatitis and other diseases and problems such as diabetes and heart disease, which can cause high levels of ALT and AST. Ask a doctor to test you for both of these conditions. It is important to rule out the big risks or to deal with them.

How to Get Liver Enzymes Back to Normal Levels

Change your lifestyle. Cut back on liver busting products such as alcohol, cigarettes and junk food. You need to remove the toxins from your body to give your liver time to recover. Drink plenty of water and fruit juices. Pack more vegetables and fruits into your diet and limit red meats.

Exercise more. By exercising more often you are burning off excess fat and cleaning out your system in another way. Fatty livers often cause elevated ALT/AST levels. Getting into shape really helps. Take it easy at first and slowly build up even going for a walk makes a difference. However, avoid strenuous exercise prior to an enzyme blood test, as it will artificially raise your ALT/AST count.

Show Your Liver Some Love With Foods That Lower ALT Liver Enzymes

Assess the medicine you take 2. Many antibiotics, cholesterol-reducing drugs, pain relief pills, anti-seizure medicine and cardiovascular drugs can cause elevated AST and ALT levels. Talk to your physician or pharmacist about other options.

Warnings

Avoid exercise if you have damaged a muscle. Let the muscle rest and repair itself. Injured muscles can cause enzyme levels to rise if stressed through exercise.


Abstract

Objective— The objective of this study was to test whether the frequent association between liver enzyme elevations and various components of the metabolic syndrome is associated with higher C-reactive protein (CRP) levels.

Methods and Results— Alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), and high-sensitivity CRP were measured in 1740 subjects. Adjusted geometric mean CRP was calculated for subjects with normal and elevated ALT and for subjects with normal and elevated Alk-P, adjusting for age, sex, smoking, physical activity, body mass index, fasting glucose, triglycerides, the presence of hypertension and low HDL cholesterol, and use of aspirin or hormone replacement therapy. Adjusted CRP levels were higher in subjects with elevated ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L, P<0.0001). Logistic regression showed that compared with subjects with normal liver function tests, the adjusted odds for high-risk CRP (>3 mg/L) were significantly higher in subjects with elevated ALT (OR, 1.5 95% CI, 1.2 to 1.9, P=0.002) or elevated Alk-P (OR, 2.1 95% CI, 1.7 to 2.6, P<0.0001).

Conclusions— Elevations of liver enzymes are associated with higher CRP concentrations. Hepatic inflammation secondary to liver steatosis is a potential contributor to the low-grade inflammation associated with the metabolic syndrome.

Elevated liver enzymes secondary to hepatic steatosis are frequent in subjects with the metabolic syndrome. We show a direct independent association between elevated liver enzymes and C-reactive protein concentrations. Thus, inflammatory processes that accompany hepatic steatosis may contribute to the systemic inflammation observed in subjects with the metabolic syndrome.

Arterial inflammation has emerged as central to the initiation and progression of atherosclerosis. Of the markers of inflammation, C-reactive protein (CRP) has been shown in multiple prospective studies to predict incident myocardial infarction, stroke, peripheral vascular disease, and sudden cardiac death. 1,2

Obesity and the metabolic syndrome are associated with chronic inflammatory response, characterized by abnormal cytokine production, increased acute phase reactants, and activation of inflammatory signaling pathways. 3 Recent studies have shown that elevated CRP is strongly associated with various characteristics of the metabolic syndrome. 4–6 A growing body of evidence implicates adipose tissue as a major regulator of chronic low-grade inflammation in patients with the metabolic syndrome. Adipose tissue produces proinflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, 3,5,7,8 and is considered an important source of basal production of interleukin-6, the chief stimulator of the production of CRP in the liver. 9

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are highly prevalent diseases that accompany the epidemic of obesity and the metabolic syndrome. 10–13 It is estimated that 25% of the American adult population has NAFLD. 14 Many studies have shown a strong association between components of the metabolic syndrome and both NAFLD and NASH. 10,12,13,15,16

Current understanding of the progression of NAFLD and NASH involves a “2-hit” hypothesis in which the initial metabolic disturbance causes steatosis and a second pathogenic stimulus causes oxidative stress, reactive oxygen species formation, and cytokine production. 10,11,17,18 Thus it has been suggested that inflammatory processes that occur in the liver contribute to the systemic inflammation that characterizes the metabolic syndrome. 19

Elevated serum alanine aminotransferase (ALT) levels is the most common liver abnormality in NAFLD and NASH, whereas alkaline phosphatase (Alk-P) and γ-glutamyltransferase are less frequently elevated. 20 NAFLD is a common explanation for abnormal liver tests results and accounts for asymptomatic elevation of aminotransferase levels in up to 90% of cases. 21

Although subjects with characteristics of the metabolic syndrome frequently have abnormal liver function tests, 10,12,13,15,16 there are no data on the association between elevated liver function tests (a crude marker of NAFLD) and metabolic abnormalities in relation to markers of inflammation. The aim of this study was to examine the relationship between abnormal liver function tests and CRP levels in middle-aged subjects with characteristics of the metabolic syndrome.

Methods

Subjects

We studied middle-aged subjects who reported to the Rambam Center for Preventive Medicine for investigation of cardiovascular risk factors. A complete medical history was taken by a physician. Subjects with known inflammatory disease and coronary disease and subjects using stains or with alcohol consumption ≥40 g per week were excluded. The investigational review committee on human research approved the study. All subjects enrolled in the study signed a statement agreeing to the use of their medical information for research purposes.

Definitions

Diagnosis of the metabolic syndrome was based on the recent Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Criteria. 22 The following cutoff limits were used: (1) systolic blood pressure≥130 mm Hg, diastolic blood pressure≥85 mm Hg , or on antihypertensive medication (2) triglyceride≥1.7 mmol/L (150 mg/dL) (3) low HDL cholesterol≤1.0 mmol/L (40 mg/dL) for men and ≤1.3 mmol/L (50 mg/dL) for women and (4) fasting glucose≥6.1 mmol/L (110 mg/dL). Because waist circumference was not measured in all subjects, we used a body mass index (BMI) cut point ≥30 kg/m 2 for obesity, as suggested by the recent World Health Organization criteria for diagnosis of the metabolic syndrome. 23 Subjects with ≥3 of the above criteria were diagnosed as having the metabolic syndrome.

Cigarette smoking was trichotomized into “never,” “past,” or “current” by use of standard questionnaire. For leisure time physical activity, we considered 3 categories (never or rarely, mild, and intensive or competitive).

Elevated ALT values were defined as >500 nkat/L (30 U/L) for men and >317 nkat/L (19 U/L) in women, based on the cutoff values provided by Prati et al. 24 These cutoff values increase the sensitivity for detection of patients with liver injury (primarily patients with hepatic steatosis). 24 Using these cutoff values corresponded approximately to the upper quartile in the study population (22% of men and 28% of women were classified as having elevated ALT values). Because cutoffs for elevated Alk-P have not been clearly defined, elevated Alk-P levels were defined as the upper quartile of Alk-P in the study population.

Laboratory Measurements

Venous blood samples were collected from each subject after a 12-hour fast and used for assay of glucose, total and HDL cholesterol, triglycerides, ALT, and Alk-P using Hitachi 911 automate and Boehringer Mannheim reagents. The intra-assay coefficients of variation for ALT and Alk-P were 4.4% and 5.0%, respectively.

CRP was measured with latex-enhanced immunonephelometry on a Behring BN II Nephelometer (Dade Behring). In this assay, polystyrene beads coated with mouse monoclonal antibodies bind CRP present in the serum sample and form aggregates. The intensity of the scattered light is proportional to the size of the aggregates and thus reflects concentration of CRP present in the sample. The intra-assay and interassay coefficients of variation for CRP were 3.3% and 3.2%, respectively. The lower detection limit of the assay was 0.15 mg/L.

Statistical Methods

The distribution of CRP levels was highly skewed. Therefore, logarithmically transformed values of CRP (ln CRP) were used in all analyses, with results expressed as geometric means.

Geometric means of CRP were adjusted for age, sex, level of physical activity, smoking status, components of the metabolic syndrome (presence of obesity, glucose intolerance, hypertension, low HDL-cholesterol, and elevated triglycerides), and use of hormone replacement therapy (HRT) and aspirin, using ANCOVA, under a general linear model. In additional models, geometric means of CRP were calculated using metabolic risk factors as continuous variables (BMI, fasting glucose, systolic blood pressure, HDL-cholesterol, and triglycerides).

In addition, geometric means of CRP were calculated using 2-way ANCOVA under a general linear model with ln CRP as the dependent variable, liver function tests (normal or elevated) as 1 factor, and the severity of metabolic abnormalities as the other (0 characteristics of the metabolic syndrome, 1 or 2 characteristics, and ≥3 characteristics). Similar models were fitted with liver function tests as 1 factor and levels of adiposity as the other (normal weight, overweight, and obese). The P-value for the main effect in these models is reported.

Multivariate logistic regression models were used to examine the association between the metabolic syndrome and high-risk CRP, defined as CRP >3.0 mg/L based on the recent American Heart Association/Centers for Disease Control and Prevention consensus recommendations, 25 in relation to liver function test status. These logistic regression models were used to calculate the probability of a high-risk CRP for each patient, and receiver operating characteristic (ROC) curves were constructed for each of these models. The discriminant accuracy of each logistic model was quantified in terms of the area under these curves. 26,27 Differences were considered significant at the 2-sided P<0.05 level. All statistical analyses were performed using the SPSS statistical software (Version 11.5).

Results

The study population included 1740 subjects (mean age 49±10 years, 61% males). The majority of subjects (65.5%) were overweight or obese (BMI≥25 kg/m 2 ), and 258 (14.8%) had the metabolic syndrome. The clinical characteristics of the study participants, according to the number of elevated liver function tests, are presented in Table 1. The prevalence of positive criteria for all components of the metabolic syndrome was higher in subjects with elevated ALT and in subjects with elevated Alk-P (Table 2).

TABLE 1. Clinical and Biochemical Characteristics of the Study Participants

TABLE 2. Positive Criteria for Components of the Metabolic Syndrome According to Liver Function Tests Category

Adjusted geometric mean CRP levels were significantly higher in subjects with elevated ALT or elevated Alk-P (Figure 1). The analyses were repeated using continuous rather than dichotomous variables for all components of the metabolic syndrome (BMI, systolic blood pressure, triglycerides, HDL cholesterol, and fasting glucose). In the continuous variable models, the adjusted geometric mean CRP was also higher in patients with elevated ALT (2.21 versus 1.94 mg/L, P=0.028) or elevated Alk-P (2.58 versus 1.66 mg/L, P<0.0001).

Figure 1. Adjusted geometric mean CRP levels and 95% CIs according to liver function tests status. CRP levels were adjusted for age, sex, smoking status, physical activity, components of the metabolic syndrome (obesity, glucose intolerance, hypertension, low HDL-cholesterol, and high triglycerides), and use of HRT and aspirin using ANCOVA under a general linear model. Alk-P indicates alkaline phosphatase.

Using the same models, we tested the significance of trends for increasing CRP levels across increasing quartiles of liver function tests. CRP levels increased with increasing quartiles of both ALT (P for trend=0.005) and Alk-P (P for trend <0.0001).

There was a significant increase in CRP levels with increasing number of abnormal liver function tests. The adjusted geometric mean CRP was 1.78 mg/L (95% CI, 1.68 to 1.89) in subjects with normal ALT and Alk-P 2.29 mg/L (95% CI, 2.12 to 2.48) in subjects with elevated ALT or Alk-P and 2.75 mg/L (95% CI, 2.29 to 3.25) in subjects with both elevated ALT and Alk-P (P for trend <0.0001).

Adjusted geometric mean CRP levels were also computed in analyses in which study participants were stratified into 6 groups according to liver function tests status (normal or elevated) and 3 categories of adiposity. Two-way ANCOVA main effects indicated that elevated ALT (P=0.01) and the level of adiposity (P<0.0001) were significantly associated with increased CRP levels. There were no significant interactions (P=0.80), indicating that the effects were additive. Figure 2A shows adjusted geometric mean CRP levels obtained from the 2-way ANCOVA model using the main effects of Alk-P status (P<0.0001) and the level of adiposity (P<0.0001). For each level of adiposity, the adjusted geometric mean CRP level was lowest among subjects with normal alkaline phosphates and highest among subjects with elevated Alk-P.

Figure 2. Adjusted geometric mean CRP levels according to Alk-P levels and categories of adiposity (normal weight, overweight, and obese A) or number of components of the metabolic syndrome (0 components, 1 or 2 components, and ≥3 components B). Alk-P indicates alkaline phosphatase.

Similar results were obtained when subjects were classified according to ALT status and the severity of metabolic abnormalities (elevated ALT main effect P<0.0001 metabolic abnormalities main effect P<0.0001). Figure 2B shows adjusted geometric mean CRP levels obtained from the 2-way ANCOVA model using the main effects of Alk-P status (P<0.0001) and the number of metabolic abnormalities (P<0.0001).

Multivariate logistic regression models were developed to determine the ability of elevated liver function tests to predict high-risk CRP (>3 mg/L). Compared with subjects with normal liver function tests, the adjusted odds for high-risk CRP level were significantly higher in subjects with either elevated ALT (OR, 1.5 95% CI, 1.2 to 1.9, P=0.002) or elevated Alk-P (OR, 2.1 95% CI, 1.7 to 2.6, P<0.0001). The area under the ROC curve of the logistic model for high-risk CRP using the presence of the metabolic syndrome data alone was 0.57±0.07. The area under the ROC curve increased with the addition of ALT data (0.61±0.07) and with the addition of Alk-P data (0.69±0.06).

Discussion

The results of this study show a direct association between elevated liver function tests (defined as liver enzyme levels in the upper quartile of the study population) and serum CRP concentrations. Elevation of liver function tests was associated with increasing number of all components of the metabolic syndrome, indicating that they mainly represent NAFLD. However, the association between elevated liver function tests and CRP was independent of the presence of metabolic abnormalities and other factors known to influence CRP levels, such as smoking, level of physical activity, and HRT. The association between liver enzyme abnormalities and increased CRP concentrations raises the possibility that inflammatory processes that accompany NAFLD contribute to the systemic inflammation observed in subjects with obesity and other characteristics of the metabolic syndrome.

Our study has several important limitations. We assume that most cases of elevated liver enzymes are secondary to NAFLD. There are several reasons for this hypothesis. First, biopsy and ultasonographic studies of patients referred for unexplained aminotransferase elevations indicate that these cases are caused by fatty infiltration of the liver in 90% of cases. 24,28,29 Second, in our study population, there was a strong relationship between elevated liver enzymes and all components of the metabolic syndrome (Table 2). Notwithstanding, tissue samples for histology were not collected and, therefore, the true cause of liver enzyme elevations in the study participants cannot be determined with certainty. In addition, the Adult Treatment Panel III definition of the metabolic syndrome used in our study is weakly correlated with direct measurements of insulin resistance. 30

The association between NAFLD and obesity, diabetes mellitus, hypertriglyceridemia, and hypertension is well established, 10,12,13,15,16 and the simultaneous presence of several metabolic abnormalities increases the risk of more advanced stages of liver disease. 13 CRP levels are elevated in metabolic disorders such as obesity, glucose intolerance, and hypertriglyceridemia. 4,31,32 There is no consensus regarding the mechanism for the association between metabolic disorders and chronic subclinical inflammation, 19 and several possible explanations have been suggested. These include release of proinflammatory cytokines from adipose tissue 5,8,33 metabolic abnormalities associated with insulin resistance, including hyperglycemia, 34 elevated free fatty acids, and endothelial dysfunction and primary insulin resistance independent of its associated metabolic abnormalities. 35

Although the liver is recognized as a major source of inflammatory mediators, it is generally assumed that hepatic production of CRP in subjects exhibiting metabolic abnormalities that characterize insulin resistance occurs under the influence of cytokines produced in other tissues. 33,36 However, inflammatory processes occur in the liver in response to fatty infiltration independent of extra hepatic stimulation. 18,37,38

The liver has one of the largest resident population of macrophages (Kupffer cells), which are key components of the innate immune systems. Hepatic macrophages generate various inflammatory mediators and cytokines that modulate the phenotype of neighboring hepatocytes and other immune cells that travel through the liver. 38 Similar to infiltration of lipoprotein particles into the arterial wall, fat accumulation in the liver stimulates hepatic cytokine production, which could further contribute to the increased CRP levels. For example, the production of tumor necrosis factor-α is one of the earliest events in NAFLD, triggering the production of other cytokines that together recruit inflammatory cells, promote hepatocyte injury, and initiate a healing response. 18 Histological evidence of mononuclear or polymorphonuclear cell infiltration (or both) is characteristic of the progression of simple steatosis to NASH, 11 and the presence of greater number of characteristics of the metabolic syndrome is associated with more severe necroinflammatory activity in liver biopsies. 13 Animal studies suggest that hepatic macrophages might be responsible in part for the obesity-associated cytokine production in peripheral tissues. 37

The results of this study suggest that liver inflammation secondary to NAFLD contributes to the subclinical systemic inflammation in individuals with features of the metabolic syndrome. Previous studies indicate that mild increases in liver enzyme levels should not be interpreted as nonspecific biochemical interference, especially in the presence of features of the metabolic syndrome, 24 because they correspond to typical histopathologic lesions. 28,39,40 Given that CRP levels provide additional prognostic information regarding subsequent cardiovascular events in people with the metabolic syndrome, 6,32,41 the results of this study suggest that these minor liver abnormalities are also relevant in the context of cardiovascular risk.

Conclusion

Mild elevations in liver enzymes are associated with higher plasma CRP concentrations. Hepatic inflammation secondary to NAFLD is a potential contributor to the chronic low-grade inflammation associated with metabolic risk factors and the metabolic syndrome.


Liver Function Tests Explained

Lab tests are often used to confirm a diagnosis (along with history and physical exam) and to monitor disease and treatment. Many lab tests measure enzyme levels. This is because when tissues are damaged cells die and enzymes are released into the blood. Levels of these enzymes are tested for, and these tests are often referred to as liver function tests. An organ system as complex as the liver will often be evaluated using several tests. This is because more than one system may release the same enzyme when the tissue is damaged. Therefore, when determining how the liver is working, and what may be causing problems, there are several tests that may be done together and are collectively known as "liver function tests."

Common liver function tests are AST (aspartate transaminase), also known as SGOT (serum glutamic-oxaloacetic transaminase), and ALT, (alanine transaminase) also known as SGPT (serum glutamic-pyruvic transaminase). Together the AST and ALT will tell if there is liver tissue damage or inflammation. ALT is more specific to liver damage than AST. It is not unusual to find mild elevations (up to 2 times normal) of AST and ALT. Levels of AST and ALT more than two times normal, however, are generally considered to be significant and require further investigation.

Alkaline phosphatase is another test that may be done if there is concern about the liver, and may indicate obstruction of the bile drainage system.

LDH (lactic acid dehydrogenase) is a non-specific enzyme that may be increased when the liver is compromised.

GGT (gamma glutamyl transferase) is an enzyme whose levels are measured to screen for liver disease and to monitor cirrhosis (hardening or scarring of the liver, especially from alcoholism). It is also helpful in diagnosing blockage of ducts that drain bile from the liver to the intestines.

In addition, bilirubin is also used to evaluate the liver. Bilirubin is not an enzyme. It is a product of the breakdown of red blood cells (RBCs) by the liver. Levels of bilirubin may increase if the liver is not functioning or there is an excess of RBCs destroyed. Levels may also increase if there is a blockage of the ducts that carry bile from the liver. Urine tests for urobilinogen, a by-product of bilirubin metabolism in the digestive tract, can be helpful in determining if the symptoms are related to RBC destruction, liver disease or obstructed ducts.

Viral hepatitis (A, B, C, and D) tests may be run to rule out a viral infection. These assays test for the presence of virus and antibodies in the blood. While the lab tests look at what is going on in cells, imaging studies look at the anatomy of organs.

Ultrasound is used often to look for gallstones and inflammation of the liver and gall bladder. It can also detect masses that may be present in or around the liver. Similarly, CT (computerized tomography) gives a picture of the inside of the body.

Doing a biopsy looks at the tissue itself, taking small pieces and examining them with a microscope.

It is the pattern of these tests' results that are used to determine how the liver is functioning, and what may be causing any problems. Don't hesitate to talk to your physician about any tests that are done, or to ask what they are being used for, (monitoring or diagnosing) what the results are, and how those results are being interpreted.


How Long Does It Take to Lower Liver Enzymes?

In most cases, elevated liver enzymes will not go down overnight. However, commitment to lifestyle changes can bring down your liver enzymes in a shorter time frame than you may think.

Research shows it may not take long at all to bring down elevated liver enzymes. A team of researchers University of Sydney and Westmead Hospital in Sydney, Australia evaluated the impact of exercise regimens on patients with elevated liver enzymes and signs of metabolic syndrome. Results showed that within just a few months, the risk of high alanine aminotransferase decreased by 70% in comparison to controls. (14)

In the study assessing probiotic supplementation discussed above, participants saw a decrease in liver enzymes in just 5 days! (7)


Watch the video: Liver and pancreatic enzymes explained. AST, ALT, GGT, ALP, Amylaseu0026 Lipase (November 2021).