Mildly Elevated Liver Transaminase Levels in the Asymptomatic Patient

PAUL T. GIBONEY, M.D.

Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal serious underlying conditions or have transient and benign etiologies. Potential causes of liver transaminase elevations include viral hepatitis, alcohol use, medication use, steatosis or steatohepatitis, and cirrhosis. The history should be thorough, with special attention given to the use of medications, vitamins, herbs, drugs, and alcohol; family history; and any history of blood-product transfusions. Other common health conditions, such as diabetes, heart disease, and thyroid disease, can cause or augment liver transaminase elevations. The recent American Gastroenterological Association guideline regarding the evaluation and management of abnormal liver chemistry tests proposes a practical, algorithmic approach when the history and physical examination do not reveal the cause. In addition to liver chemistries, an initial serologic evaluation includes a prothrombin time; albumin; complete blood count with platelets; hepatitis A, B, and C serologies; and iron studies. Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity. If elevations persist after an appropriate period of observation, further testing may include ultra-sonography and other serum studies. In some cases, biopsy may be indicated.

Hepatic transaminase tests such as alanine transaminase (ALT) and aspartate transaminase (AST) often are part of standard laboratory panels in asymptomatic outpatients, similar to screening tests for blood donors and for life insurance applicants. The evaluation of an abnormal ALT or AST level in an asymptomatic patient therefore is a common challenge encountered by primary care physicians.

According to the American Gastroenterological Association (AGA), 1 to 4 percent of the asymptomatic population may have elevated serum liver chemistries.¹ This is consistent with the usual definition of an elevated transaminase level of the top 2.5 percent of the population range. Although one study² of 19,877 asymptomatic young Air Force trainees found that only 0.5 percent had elevated ALT levels, physicians who have more patients with obesity, diabetes, and hyperlipidemia will have to address this issue more often.

Given the frequency of this problem, physicians should develop an informed approach to the investigation of transaminase elevations. An audit of primary care practices found that these abnormalities are not always investigated appropriately and that opportunities to intervene in treatable cases sometimes are missed. ³ No controlled clinical trials have compared approaches to the management of abnormal transaminase levels. However, the AGA recently published a technical review¹ and a position statement⁴ on the evaluation of liver chemistry tests. This article reviews the interpretation of ALT and AST levels and summarizes the AGA recommendations on addressing reported elevations.

Key clinical recommendation	Label	References
An algorithmic approach to evaluating mildly abnormal liver functions is recommended.	C	1
In the asymptomatic patient with negative serum testing and mild transaminase elevations, a period of lifestyle modification can be tried.	C	1
If abnormalities persist at the six-month follow-up visit, an ultrasonography of the liver is the recommended imaging modality.	C	1
ALT and AST are not useful screening tests in an otherwise healthy population.	C	1,10
The AST/ALT ratio is only somewhat helpful in diagnosis.	C	5,7

Markers of Hepatic Injury and Necrosis

ALT and AST are two of the most reliable markers of hepatocellular injury or necrosis. Their levels can be elevated in a variety of hepatic disorders. Of the two, ALT is thought to be more specific for hepatic injury because it is present mainly in the cytosol of the liver and in low concentrations elsewhere. AST has cytosolic and mitochondrial forms and is present in tissues of the liver, heart, skeletal muscle, kidneys, brain, pancreas, and lungs, and in white and red blood cells. AST is less commonly referred to as serum glutamic oxaloacetic transaminase and ALT as serum glutamic pyruvic transaminase.

Although levels of ALT and AST can be extremely elevated (exceeding 2,000 U per L in cases of hepatocyte injury and necrosis related to drugs, toxins, ischemia, and hepatitis), elevations less than five times the upper limit of normal (i.e., about 250 U per L and below) are much more common in primary care medicine. The range of possible etiologies at this level of transaminase elevation is broader (Table 1^5,6) and the tests less specific. It also is important to recall that patients with normal ALT and AST levels can have significant liver disease in the setting of chronic hepatocyte injury (e.g., cirrhosis, hepatitis C).

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The ratio of AST to ALT has some clinical utility, but has important limitations. In many forms of acute and chronic liver injury or steatosis (fatty infiltration of the liver), the ratio is less than or equal to 1. This is particularly true in patients with hepatitis C. However, an AST/ALT ratio greater than 2 characteristically is present in alcoholic hepatitis. A recent study⁷ of 140 patients with nonalcoholic steatohepatitis (NASH; confirmed by liver biopsy) or alcoholic liver disease found a mean AST/ALT ratio of 0.9 in patients with NASH and 2.6 in patients with alcoholic liver disease. Within the population studied, 87 percent of patients with an AST/ALT ratio of 1.3 or less had NASH (87 percent sensitivity, 84 percent specificity). The severity of NASH as measured by the degree of fibrosis increased, as did the AST/ALT ratio. A mean ratio of 1.4 was found in patients with cirrhosis related to NASH. Wilson’s disease, a rare problem, can cause the AST/ALT ratio to exceed 4.⁵ While these ratios are suggestive of certain conditions, there is too much overlap between groups to rely on them exclusively when making a diagnosis.

Lactate dehydrogenase (LDH) is a less specific marker of hepatocellular necrosis and usually does not add diagnostic information to that obtained with ALT and AST testing. An exception to this is the transient but massive rise of LDH in cases of ischemic hepatitis and its sustained elevation that, along with elevated alkaline phosphatase levels, suggests malignant infiltration of the liver.⁵

Elevations of ALT and AST are not exclusive to liver pathology. Hyperthyroidism has been found in several studies to increase serum levels of liver enzymes including ALT and AST.⁸ Genetic influences on the level of ALT also are possible. A study⁹ of Danish twins showed that genetic factors accounted for 33 to 66 percent of the variation in ALT, gamma glutamyl transpeptidase, LDH, and bilirubin in patients 73 to 94 years of age. The AGA technical review states that serum ALT has diurnal variation, may vary day to day, and may be affected by exercise. It also notes that serum AST may be 15 percent higher in black men than white men.¹

Another cause of elevated liver transaminase levels is muscle injury. Strenuous exercise or myopathy can cause elevations (especially of AST) without causing any other symptoms. A creatine kinase or other muscle marker can be obtained to confirm or exclude such a process.

Annual screening of healthy, asymptomatic patients for liver disease using ALT and AST levels is not useful. A Japanese study¹⁰ assessed the accuracy of ALT and AST for detecting hepatitis C, excess alcohol use, and fatty liver disease in male bank employees and found the positive predictive value of the test to be low. Only 3.9 percent of the men with an abnormal ALT level had hepatitis C; 8 percent were excessive users of alcohol; and 35.7 percent had fatty liver.

Management

A thorough medical history and physical examination are the cornerstone of the evaluation of patients with mildly elevated liver transaminase levels.¹ The history should attempt to identify risk factors for disease, with special attention directed toward family history, medications, vitamins, herbal supplements, drug use, alcohol use, abnormal liver testing, blood-product transfusions, and symptoms of liver disease. Table 2⁶ lists selected medications and herbal supplements that may cause elevated transaminase levels. Physicians should ask patients directly about their use of illicit drugs, herbal supplements, and other alternative “supplements” because these sometimes are omitted from the patient’s initial response to questions.

The presence of other significant health conditions that can cause or augment liver transaminase elevations also should be noted; examples are diabetes, heart disease (including congestive heart failure), thyroid disease, muscle disease, and cancer. Physical findings and sequelae of liver dysfunction are given in Table 3.

Once the history and physical examination are completed, additional testing can help discern the etiology of the transaminase elevation (Figure 1). ⁴

INITIAL LABORATORY EVALUATION

Additional laboratory tests should be obtained when the history and physical examination show no obvious etiology for ALT and AST elevations. Ferritin, total iron-binding capacity, and serum iron can be used to look for hemochromatosis, while hepatitis A, B, and C serologies are used to rule out acute or chronic hepatitis.

Despite the emergence of widespread vaccination, hepatitis B remains a common cause of chronic liver disease in adults. Testing for hepatitis C is essential because its incidence has increased in the past decade, and new treatment strategies have been developed that can address this frequently missed problem.¹¹

A prothrombin time (PT) and serum albumin should be ordered to identify patients with abnormalities of protein synthesis and liver function. Evaluation should be accelerated for patients with impaired hepatic synthetic function. A complete blood count with platelets also should be ordered. In addition to ruling out infection, neutropenia or thrombocytopenia can, along with an elevated PT, suggest advanced liver disease. An elevated mean red cell volume suggests heavy alcohol intake. Alkaline phosphatase and bilirubin are markers for hepatic cholestasis and should be ordered as part of the initial laboratory evaluation. While sometimes useful, they often are normal in the presence of hepatic injury.

LIFESTYLE MODIFICATION

If the patient is asymptomatic and the initial serum testing is negative, a period of lifestyle modification can be attempted. Effective lifestyle modification includes complete abstinence from alcohol, control of diabetes and hyperlipidemia, weight loss in overweight patients, and stopping or changing potentially hepatotoxic medications and supplements. Such lifestyle changes directly impact several of the causes of mild transaminase elevation (Table 1).^5,6 These seemingly small modifications may be all that is needed to correct the abnormalities.

FOLLOW-UP AND IMAGING STUDIES

A repeat set of liver chemistries should be obtained after six months. If the patient’s presentation changes or the physician has concern for an evolving process, shorter intervals can be used. If abnormalities persist at the six-month follow-up visit, ultra-sonography of the liver is recommended. Computed tomography of the abdomen also is used in this setting, although clinical trials have not demonstrated an advantage of this more expensive modality.

Steatohepatitis (or nonalcoholic fatty liver disease) often is discovered by imaging. This condition may be the most frequent cause of mild liver chemistry elevations and is especially common in patients who are obese, and those who have diabetes or hyperlipidemia. One study¹² of patients referred to a hospital-based gastroenterology practice found that in 83 percent of patients with elevated transaminase levels whose serum evaluation was otherwise negative, liver biopsy revealed steatosis or steatohepatitis. In 10 percent of the patients, however, liver biopsy was normal—a reminder that, at times, mildly elevated transaminase levels do not represent any underlying pathology. Excellent reviews of the management of nonalcoholic fatty liver disease have been published.^13,14

If the diagnosis is not apparent from the ultrasound examination, further testing is suggested for alpha₁-antitrypsin deficiency (alpha₁-antitrypsin levels), Wilson’s disease (serum ceruloplasmin), celiac disease (antigliadin and anti-endomysial antibody), and autoimmune hepatitis (antinuclear antibody, anti–smooth-muscle antibody), as well as for nonhepatic causes of transaminase elevation. According to the AGA, the decision to perform a liver biopsy needs to be made on an individual basis, taking into consideration the patient’s age, lifestyle, liver chemistry abnormalities, desire for prognostic information, and associated comorbid conditions.¹ Only with chronic mild transaminase elevations would an asymptomatic patient be considered a possible candidate for biopsy.

Aspartate Aminotransferase (AST) Test (aka SGOT): High vs. Low Levels

Written by WebMD Editorial Contributors

• Why Would I Need This Test?
• How Do I Prepare?
• What Happens During the Test?
• What Are the Risks?
• What Do the Results Mean?
• Will I Take Other Tests?
• More

The aspartate aminotransferase (AST) test is a blood test that checks for liver damage. Your doctor might order this test to find out if you have liver disease and to monitor your treatment.

Your liver is an organ that has many important jobs.

It makes a fluid called bile that helps your body digest food. It also removes waste products and other toxins from your blood. It produces proteins, as well as substances that help your blood clot. Alcohol or drug use and diseases such as hepatitis can damage your liver and keep it from doing these jobs.

AST is an enzyme your liver makes. Other organs, like your heart, kidneys, brain, and muscles, also make smaller amounts. AST is also called SGOT (serum glutamic-oxaloacetic transaminase).

Normally, AST levels in your blood are low. When your liver is damaged, it puts more AST into your blood, and your levels rise.

A high AST level is a sign of liver damage, but it can also mean you have damage to another organ that makes it, like your heart or kidneys. That’s why doctors often do the AST test together with tests of other liver enzymes.

Your doctor can order an AST test if you have symptoms of liver damage, such as:

• Yellow skin or eyes, called jaundice
• Tiredness
• Weakness
• Swollen belly
• Stomach pain
• Appetite loss
• Itchy skin
• Dark-colored urine
• Light-colored poop
• Swelling in your legs and ankles
• Bruises

Other reasons to have this test:

• You’ve been exposed to the hepatitis virus.
• You drink a lot of alcohol.
• You take medicine that’s known to damage the liver.
• You have a family history of liver disease.
• You have obesity.
• You have diabetes or metabolic syndrome.
• You’ve had nonalcoholic fatty liver disease.

Your doctor might also want you to get this test to see if treatments you take for liver disease are working.

The AST test is also part of a comprehensive metabolic panel — a blood test your doctor does as part of a routine exam.

You don’t need any special preparation for the ALT test.

Tell your doctor what drugs or supplements you take. Some medicines can affect the results of this test.

A nurse or lab tech will take a sample of your blood — usually from a vein in your arm. They will first tie a band around the upper part of your arm to make your vein fill with blood and swell up. Then they will clean an area on your arm with an antiseptic and put a needle in one of your veins. Your blood will go into a vial or tube.

The blood test should only take a couple of minutes. After your blood is drawn, the lab tech will take off the band and pull out the needle. They’ll put a piece of gauze and a bandage where the needle went in to stop the bleeding.

The AST blood test is safe. Risks are usually minor, and can include:

• Bleeding
• Bruising
• Infection
• Pain when the needle is inserted
• Fainting or feeling dizzy

You should have the results in about a day. They are given in units per liter (units/L). Normal ranges are:

• Males: 10 to 40 units/L
• Females: 9 to 32 units/L

Your exact range may depend on which lab your doctor uses. Talk with them about the specifics of your case.

Higher-than-normal AST levels can be caused by:

• Chronic (ongoing) hepatitis
• Cirrhosis (long-term damage and scarring of the liver)
• Blockage in the bile ducts that carry digestive fluid from the liver to the gallbladder and intestine
• Liver cancer

Very high AST levels can be caused by:

• Acute viral hepatitis
• Damage to the liver from drugs or other toxic substances
• A blockage in blood flow to the liver

Your doctor might also compare your AST and ALT levels. If you have liver disease, usually your ALT level will be higher than your AST level.

These other conditions not tied to your liver can also raise your AST level:

• Burns
• Heart attack
• Intense exercise
• Muscle injury
• Pregnancy
• Pancreatitis
• Seizures
• Surgery

Some diseases or medicines you take can cause a “false positive” result on the AST test. This means your test is positive, even though you don’t have liver damage. Any of these can cause a false positive result:

• Diabetic ketoacidosis (Your body can’t make enough insulin, which helps sugar enter your cells.)
• Some antibiotics, such as erythromycin estolate or para-aminosalicylic acid (Paser)

AST is usually done as part of a group of liver function tests called a liver panel. It’s often ordered with a test for alanine aminotransferase (ALT), another liver enzyme.

ALT is more accurate than AST at detecting liver disease. It can more accurately show whether the problem is in your liver or in another part of your body, like your heart or muscles.

Your doctor can compare the amount of ALT to AST in your blood to find out whether you have liver damage or a problem with another organ, such as your heart.

Your doctor might also do other tests of enzymes and proteins your liver makes, such as:

• Alkaline phosphatase (ALP)
• Bilirubin
• Total protein

Talk with your doctor to make sure you understand all of your liver test results. Also find out how these results might affect your treatment.

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COMPLEX “GENERAL CLINICAL” (ALT, AST, total bilirubin, glucose, total cholesterol, total protein, creatinine, urea) in Izhevsk

Alanine aminotransferase (ALT, AlAT) is synthesized intracellularly, and normally only a small part of this enzyme enters the blood. If the liver is damaged (with hepatitis, cirrhosis of the liver), this enzyme enters the bloodstream.

ALT levels can also rise with myocardial infarction, which is always accurately detected by tests.

An increase in ALT greater than an increase in AST is indicative of liver damage; if the AST index rises more than the ALT rises, then this, as a rule, indicates problems with myocardial cells.

An increase in ALT activity can be caused by taking certain drugs (mostly due to toxic effects on the liver).

A decrease in plasma ALT activity is possible with renal failure, pyridoxine deficiency, after repeated hemodialysis procedures, during pregnancy.

Aspartate aminotransferase (AST, AST) is synthesized intracellularly, and normally only a small part of this enzyme enters the blood. With damage to the myocardium, the liver, this enzyme enters the bloodstream. Therefore, an adult blood test will quickly show the presence of the enzyme.

An increase in AST that exceeds an increase in ALT is characteristic of damage to the heart muscle; if the ALT index is higher than the AST, then this, as a rule, indicates the destruction of liver cells.

Total bilirubin is considered a product of the breakdown of myoglobin, cytochromes and hemoglobin in some cells of the spleen, liver and reticuloendothelial system. It is one of the nodal components of bile. Contains bilirubin in the form of fractions in the blood serum. Fractions can be direct (conjugated or bound) and indirect (unbound or free) bilirubin, together making up total bilirubin. The definition of direct and total bilirubin is traditionally used, which shows the amount of free bilirubin that is practically insoluble in water.

Indications for use:

• Liver diseases;
• Hemolytic anemia;
• Clinical signs of jaundice.

Glucose is considered a key indicator of active carbohydrate metabolism, and determining its actual level in the body is a mandatory step in the process of diagnosing complex diseases, such as diabetes. The indicator of glucose concentration is regulated by hormones, which is why an analysis for hormones is needed here. So, insulin, which is the main hormone in the pancreas, in case of its own deficiency, affects the increase in glucose, so the cells starve. For adults, a certain range of 3.9 is considered normal.-5.8 mmol / liter, while the indicator can increase during pregnancy or after 60 years.

Cholesterol (cholesterol) is an organic compound and an essential component of active fat metabolism. It is used for the process of building cell membranes, participates in the actual synthesis of sex hormones and vitamin D, and is a precursor of bile in the liver.

In the blood, cholesterol can be contained in the form of total cholesterol, as well as low or high density lipoproteins. The procedure for the synthesis of cholesterol occurs in individual liver cells, it is slightly produced in the adrenal glands, skin layers and intestinal walls. Partially, cholesterol comes with all kinds of foods. Paid blood tests will help to find out its level.

The total protein is an organic polymer composed directly of various amino acids. Proteins are involved in most biochemical reactions of the body as catalysts, are responsible for the transport of various substances and active drugs, and are also involved in providing high-quality immune protection. The generalized (total) concentration of proteins in the blood is determined by the existing concept of “total protein”.

The procedure for determining the protein index is used to diagnose a variety of diseases of the kidneys, liver and oncological diseases called a blood test for protein.

Creatinine is the end product of the breakdown of creatine, which is released during muscle contraction, transported by the blood to the kidneys and excreted from the body through the urine. Due to the fact that creatinine is excreted through the kidneys, an increase in its content in the blood is an indicator of renal failure (such an increase indicates a violation of the filtration and excretory function of the kidneys). Thus, the concentration of creatinine in the blood reflects the balance between the rate of its formation in the muscles and the rate of renal excretion.

The main product of the protein breakdown procedure is the active substance urea , produced from ammonia by the liver. The substance is actively involved in the direct process of concentrating urine.

The urea synthesis procedure effectively neutralizes ammonia, which is an extremely toxic substance. Urea is excreted from the body through the kidneys, and the presence of elevated urea levels is a serious symptom of disorders.

A special analysis will help determine kidney disease, impaired urine flow, heart failure, malignant tumors and leukemia, fevers and burns, and severe bleeding.

Alanine aminotransferase (ALT, ALT), aspartate aminotransferase (AST, AST) – Biochemical blood test – Deciphering tests online

Alanine aminotransferase (ALT, ALT), aspartate aminotransferase (AST, AST) 9000 5

Liver tests is a set of indicators of a biochemical blood test, with which you can evaluate some of the functions of the liver. To assess the degree of damage to liver cells (hepatocytes), it is necessary to pass an analysis to determine the level of certain liver enzymes (proteins) in the blood. Damage to the wall of the hepatocyte entails an increased release of liver enzymes into the blood.

Decipher “Complete blood count”
Decipher “Complete urinalysis”

Aminotransferases are a group of enzymes that are present in the cells of all internal organs, but are most active in hepatocytes. These include alanine aminotransferase (ALT, ALT) and aspartate aminotransferase (AST, AsAT).

Aspartate aminotransferase (AST, AST)

Liver, heart, muscles, kidneys and brain are the organs with the highest amount of AST. This enzyme enters the blood when any of these organs is damaged. For example, the level of AST in the blood increases with heart attacks and muscle injuries. Aspartate aminotransferase is not considered a specific indicator of liver damage. The enzyme is a marker of the destruction of the heart muscle, and its level is assessed in myocardial infarction.

Alanine aminotransferase (ALT, AlAT)

Alanine aminotransferase is considered a specific indicator of hepatocyte destruction. It predominates to a greater extent in the cytoplasm of liver cells than in the kidneys, myocardium, pancreas or skeletal muscles.

It must be understood that ALT and AST levels do not always indicate abnormal liver function, although they are included in a group of tests called “liver tests”. Even if ALT and AST are greatly elevated, the liver may still function properly. For an accurate understanding of the reasons for the increase in ALT and AST, it is necessary to consult a doctor.

ALT and AST limits

While reference values ​​for AST and ALT may vary from laboratory to laboratory, the upper limit of normal is typically 40 units per liter of serum (blood fluid) for AST and 50 units per liter of serum for ALT.

Women tend to have lower levels of transaminases (ALT, AST) than men. In the elderly, AST and ALT levels are usually slightly higher than the normal range for adults.

In children, the level of ALT and AST in the blood is slightly higher than adult norms – this is not a pathology.

AST and ALT ranges may vary slightly depending on the technique and protocols used by various laboratories around the world. Usually laboratories indicate the range of reference values ​​​​of indicators on the test forms.

ALT/AST above normal

It must be understood that the increase in transaminases (AST and ALT) is not an independent disease – it is only a consequence of the disease. To reduce the level of AST and ALT in the blood, it is necessary to eliminate the cause of the increase in enzymes.

One of the most common causes of slight elevations in ALT and AST in asymptomatic individuals is chronic alcohol use. Many prescription drugs also cause an increase in ALT. [1]

Very high levels of ALT and AST (greater than 10 times normal) are usually associated with acute hepatitis. ALT and AST can also be severely elevated (sometimes more than 100 times normal) by exposure to drugs or other substances that are toxic to the liver, or by conditions that cause decreased blood flow to the liver.