What are liver function tests. How do ALT and AST levels indicate liver health. What other enzymes and proteins are measured in liver function tests. When are liver function tests recommended. How are liver function tests performed. What do normal liver function test results look like. How can you prepare for liver function tests.

The Importance of Liver Function Tests in Diagnosing Liver Health

Liver function tests are crucial diagnostic tools used by healthcare professionals to assess the health and functionality of the liver. These blood tests measure various enzymes, proteins, and other substances in the bloodstream that can indicate liver disease or damage. By analyzing these components, doctors can gain valuable insights into how well the liver is performing its vital functions and detect potential issues early on.

Key Components of Liver Function Tests

Liver function tests typically examine several key components, including:

• Enzymes: ALT, AST, ALP, GGT, and LD
• Proteins: Albumin and total protein
• Bilirubin
• Prothrombin time (PT)

Each of these components plays a specific role in assessing liver health and can provide valuable information about potential liver problems.

Understanding ALT and AST: The Primary Liver Enzymes

Among the various components measured in liver function tests, alanine transaminase (ALT) and aspartate transaminase (AST) are two of the most important enzymes. These enzymes are primarily found in liver cells and are released into the bloodstream when liver damage occurs.

Alanine Transaminase (ALT)

ALT is an enzyme that plays a crucial role in converting proteins into energy for liver cells. When liver cells are damaged or die, ALT is released into the bloodstream, causing levels to rise. Normal ALT levels typically range from 7 to 55 units per liter (U/L) in adults.

Aspartate Transaminase (AST)

AST is another enzyme found in liver cells, as well as in other tissues such as heart and muscle cells. It helps metabolize amino acids and is also released into the bloodstream when liver damage occurs. Normal AST levels usually range from 8 to 48 U/L in adults.

Are elevated ALT and AST levels always indicative of liver problems? While increased levels of these enzymes often suggest liver damage or disease, it’s important to note that other factors can also cause elevations. For example, intense exercise or muscle damage can lead to higher AST levels. Therefore, doctors typically consider ALT and AST results in conjunction with other liver function tests and clinical information to make an accurate diagnosis.

Other Essential Components of Liver Function Tests

While ALT and AST are crucial indicators of liver health, several other components measured in liver function tests provide valuable information about liver functionality and potential issues.

Alkaline Phosphatase (ALP)

ALP is an enzyme found in various tissues, including the liver and bones. It plays a role in breaking down proteins and is often elevated in cases of liver damage or disease, particularly when bile ducts are blocked. Normal ALP levels typically range from 40 to 129 U/L in adults.

Albumin and Total Protein

Albumin is a protein produced by the liver that plays a crucial role in maintaining fluid balance in the body and transporting various substances through the bloodstream. Total protein measures all proteins in the blood, including albumin. Low levels of albumin and total protein can indicate liver damage or disease. Normal ranges are typically 3.5 to 5.0 g/dL for albumin and 6.3 to 7.9 g/dL for total protein.

Bilirubin

Bilirubin is a yellowish pigment produced during the breakdown of red blood cells. The liver is responsible for processing bilirubin and excreting it through bile. Elevated bilirubin levels can cause jaundice and may indicate liver damage or certain types of anemia. Normal bilirubin levels usually range from 0.1 to 1.2 mg/dL.

Gamma-Glutamyltransferase (GGT)

GGT is an enzyme found in liver cells and bile ducts. Elevated levels of GGT can suggest liver or bile duct damage. Normal GGT levels typically range from 8 to 61 U/L in adults.

L-Lactate Dehydrogenase (LD)

LD is an enzyme found in various tissues, including the liver. While elevated LD levels can indicate liver damage, they can also be increased in many other disorders. Normal LD levels usually range from 122 to 222 U/L.

Prothrombin Time (PT)

PT measures how long it takes for blood to clot. The liver produces proteins necessary for blood clotting, so an increased PT may indicate liver damage. However, certain blood-thinning medications can also affect PT. Normal PT ranges from 9.4 to 12.5 seconds.

When Are Liver Function Tests Recommended?

Liver function tests are valuable diagnostic tools that can be used in various medical situations. Healthcare providers may recommend these tests for several reasons:

• Screening for liver infections, such as hepatitis
• Monitoring the progression of liver diseases like viral or alcoholic hepatitis
• Assessing the effectiveness of treatments for liver conditions
• Evaluating the severity of liver damage, particularly in cases of cirrhosis
• Monitoring potential side effects of medications that may affect liver function

Do liver function tests always indicate liver disease? It’s important to note that abnormal liver function test results don’t always signify liver disease. Various factors, including certain medications, alcohol consumption, and even intense exercise, can temporarily affect liver enzyme levels. Therefore, doctors interpret these results in the context of a patient’s overall health, medical history, and other diagnostic information.

The Liver Function Test Procedure: What to Expect

Understanding the liver function test procedure can help patients feel more prepared and comfortable when undergoing these important diagnostic tests.

Before the Test

Prior to the test, your doctor may provide specific instructions to ensure accurate results. These may include:

• Fasting for a certain period before the blood draw
• Avoiding certain medications that could affect the test results
• Informing your doctor about any current medications or supplements you’re taking

During the Test

The liver function test itself is a simple blood draw procedure:

1. A healthcare professional will clean the area, usually the inside of your elbow or back of your hand, with an antiseptic.
2. An elastic band may be tied around your upper arm to make the veins more visible and easier to access.
3. A small needle will be inserted into a vein to draw a blood sample.
4. You may feel a brief sting when the needle is inserted and removed.
5. The blood sample is collected in one or more small vials.
6. The entire process usually takes less than five minutes.

After the Test

After the blood draw:

• Pressure will be applied to the site to stop any bleeding.
• A small bandage may be placed over the area.
• You can usually resume normal activities immediately after the test.
• Results may be available within hours if analyzed on-site, or within a few days if sent to an external laboratory.

Are there any risks associated with liver function tests? While liver function tests are generally safe, there are minimal risks associated with any blood draw procedure, such as slight pain, bruising, or in rare cases, infection at the site of the needle insertion. These risks are typically minor and resolve quickly.

Interpreting Liver Function Test Results

Interpreting liver function test results requires medical expertise, as the significance of the results can vary based on individual factors and overall health status. However, understanding typical normal ranges can provide a general framework for patients to discuss their results with their healthcare providers.

Normal Ranges for Common Liver Function Tests

While normal ranges can vary slightly between laboratories, typical normal ranges for adults include:

• ALT: 7 to 55 U/L
• AST: 8 to 48 U/L
• ALP: 40 to 129 U/L
• Albumin: 3.5 to 5.0 g/dL
• Total protein: 6.3 to 7.9 g/dL
• Bilirubin: 0.1 to 1.2 mg/dL
• GGT: 8 to 61 U/L
• LD: 122 to 222 U/L
• PT: 9.4 to 12.5 seconds

Can liver function test results vary between individuals? It’s important to note that “normal” can vary based on factors such as age, gender, body mass index, and overall health status. Additionally, some people may have results outside these ranges without necessarily having liver problems. Conversely, early stages of liver disease may not always be reflected in these tests. Therefore, healthcare providers consider these results in conjunction with other clinical information to make accurate assessments.

Factors That Can Affect Liver Function Test Results

Several factors can influence liver function test results, potentially leading to abnormal readings even in the absence of liver disease. Understanding these factors can help patients and healthcare providers interpret test results more accurately.

Medications and Supplements

Certain medications and supplements can affect liver enzyme levels, including:

• Over-the-counter pain relievers like acetaminophen
• Some antibiotics and antifungal medications
• Cholesterol-lowering statins
• Certain herbal supplements and vitamins

Alcohol Consumption

Recent alcohol consumption, especially in large quantities, can temporarily elevate liver enzyme levels. Chronic alcohol use can lead to more persistent elevations and liver damage.

Exercise and Physical Activity

Intense exercise or physical activity, especially if not part of one’s regular routine, can cause temporary elevations in certain liver enzymes, particularly AST.

Body Weight

Obesity and rapid weight changes can affect liver function and enzyme levels. Non-alcoholic fatty liver disease, often associated with obesity, can lead to elevated liver enzymes.

Diet

Certain dietary factors can influence liver function test results:

• High protein intake may increase ALT levels
• Fasting can affect bilirubin levels
• Some herbal teas and supplements can impact liver enzyme levels

Medical Conditions

Various medical conditions unrelated to liver disease can affect liver function test results:

• Celiac disease
• Thyroid disorders
• Muscle disorders or injuries
• Heart conditions

How can patients ensure accurate liver function test results? To obtain the most accurate results, patients should inform their healthcare providers about all medications, supplements, recent lifestyle changes, and medical conditions before undergoing liver function tests. Following pre-test instructions, such as fasting if required, is also crucial for accurate results.

The Role of Liver Function Tests in Diagnosing and Monitoring Liver Conditions

Liver function tests play a crucial role in diagnosing and monitoring various liver conditions. By providing insights into liver enzyme levels, protein production, and other liver functions, these tests help healthcare providers identify potential liver problems and track the progression of known liver diseases.

Diagnosing Liver Conditions

Liver function tests can help diagnose or indicate the presence of several liver conditions, including:

• Hepatitis (viral, alcoholic, or autoimmune)
• Cirrhosis
• Non-alcoholic fatty liver disease
• Liver cancer
• Bile duct obstructions
• Hemochromatosis (iron overload)
• Wilson’s disease (copper accumulation)

While liver function tests alone cannot definitively diagnose these conditions, they often serve as important initial indicators that prompt further investigation.

Monitoring Liver Disease Progression

For patients with known liver conditions, regular liver function tests can help:

• Track the progression of liver disease
• Assess the effectiveness of treatments
• Detect potential complications early
• Guide treatment decisions

Assessing Medication Effects

Liver function tests are also valuable for monitoring the potential hepatotoxic effects of certain medications. This is particularly important for patients taking long-term medications known to affect the liver, such as certain antibiotics, statins, or chemotherapy drugs.

How frequently should liver function tests be performed in patients with liver conditions? The frequency of liver function tests can vary depending on the specific condition, its severity, and the treatment plan. Some patients may require monthly tests, while others may need them less frequently. Healthcare providers determine the appropriate testing schedule based on individual patient needs and clinical guidelines.

In conclusion, liver function tests, particularly measurements of ALT and AST enzymes, provide valuable insights into liver health and function. These tests, along with other components like ALP, albumin, bilirubin, and prothrombin time, offer a comprehensive picture of liver status. While abnormal results don’t always indicate liver disease, they serve as important diagnostic tools for healthcare providers. Understanding the factors that can influence test results and the role these tests play in diagnosing and monitoring liver conditions can help patients actively participate in their liver health management. Regular liver function testing, when recommended by healthcare providers, is a crucial aspect of maintaining overall health and detecting potential liver issues early.

Liver function tests – Mayo Clinic

Overview

Liver function tests are blood tests used to help diagnose and monitor liver disease or damage. The tests measure the levels of certain enzymes and proteins in your blood.

Some of these tests measure how well the liver is performing its normal functions of producing protein and clearing bilirubin, a blood waste product. Other liver function tests measure enzymes that liver cells release in response to damage or disease.

Abnormal liver function test results don’t always indicate liver disease. Your doctor will explain your results and what they mean.

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Why it’s done

Liver function tests can be used to:

• Screen for liver infections, such as hepatitis
• Monitor the progression of a disease, such as viral or alcoholic hepatitis, and determine how well a treatment is working
• Measure the severity of a disease, particularly scarring of the liver (cirrhosis)
• Monitor possible side effects of medications

Liver function tests check the levels of certain enzymes and proteins in your blood. Levels that are higher or lower than normal can indicate liver problems. Some common liver function tests include:

• Alanine transaminase (ALT). ALT is an enzyme found in the liver that helps convert proteins into energy for the liver cells. When the liver is damaged, ALT is released into the bloodstream and levels increase.
• Aspartate transaminase (AST). AST is an enzyme that helps metabolize amino acids. Like ALT, AST is normally present in blood at low levels. An increase in AST levels may indicate liver damage, disease or muscle damage.
• Alkaline phosphatase (ALP). ALP is an enzyme found in the liver and bone and is important for breaking down proteins. Higher-than-normal levels of ALP may indicate liver damage or disease, such as a blocked bile duct, or certain bone diseases.
• Albumin and total protein. Albumin is one of several proteins made in the liver. Your body needs these proteins to fight infections and to perform other functions. Lower-than-normal levels of albumin and total protein may indicate liver damage or disease.
• Bilirubin. Bilirubin is a substance produced during the normal breakdown of red blood cells. Bilirubin passes through the liver and is excreted in stool. Elevated levels of bilirubin (jaundice) might indicate liver damage or disease or certain types of anemia.
• Gamma-glutamyltransferase (GGT). GGT is an enzyme in the blood. Higher-than-normal levels may indicate liver or bile duct damage.
• L-lactate dehydrogenase (LD). LD is an enzyme found in the liver. Elevated levels may indicate liver damage but can be elevated in many other disorders.
• Prothrombin time (PT). PT is the time it takes your blood to clot. Increased PT may indicate liver damage but can also be elevated if you’re taking certain blood-thinning drugs, such as warfarin.

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Risks

The blood sample for liver function tests is usually taken from a vein in your arm. The main risk associated with blood tests is soreness or bruising at the site of the blood draw. Most people don’t have serious reactions to having blood drawn.

How you prepare

Certain foods and medications can affect the results of your liver function tests. Your doctor will probably ask you to avoid eating food and taking some medications before your blood is drawn.

What you can expect

During the test

The blood sample for liver function tests is usually drawn through a small needle inserted into a vein in the bend of your arm. The needle is attached to a small tube, to collect your blood. You may feel a quick pain as the needle is inserted into your arm and experience some short-term discomfort at the site after the needle is removed.

After the test

Your blood will be sent to a laboratory for analysis. If the lab analysis is done on-site, you could have your test results within hours. If your doctor sends your blood to an off-site laboratory, you may receive the results within several days.

Results

Normal blood test results for typical liver function tests include:

• ALT. 7 to 55 units per liter (U/L)
• AST. 8 to 48 U/L
• ALP. 40 to 129 U/L
• Albumin. 3.5 to 5.0 grams per deciliter (g/dL)
• Total protein. 6.3 to 7.9 g/dL
• Bilirubin. 0.1 to 1.2 milligrams per deciliter (mg/dL)
• GGT. 8 to 61 U/L
• LD. 122 to 222 U/L
• PT. 9.4 to 12.5 seconds

These results are typical for adult men. Normal results vary from laboratory to laboratory and might be slightly different for women and children.

Your doctor will use these results to help diagnose your condition or determine treatment you might need. If you already have liver disease, liver function tests can help determine how your disease is progressing and if you’re responding to treatment.

Elevated Liver Enzymes? Muscle Damage May Play a Role

The liver is the main “chemist” in our body. It is the primary location for the conversion of one compound to another. Because of this, the liver can be thought of as the body’s detoxifier. If you have a liver, there is no need to “detox” through juice cleanses or lengthy fasts. Your liver does that for you every day.

In order to evaluate overall liver function, InsideTracker tests AST, ALT, GGT, and albumin. The first three are enzymes, and albumin is the main protein produced by the liver. Albumin functions as the primary transporter of hormones, drugs, and other compounds in our blood and helps to control the pressure in our circulatory system. Albumin levels outside of the normal range are rare for InsideTracker users. Low levels are likely caused by severe liver damage and high levels are typically due to dehydration or excessively high protein intake. Both high and low require medical attention.

The other 3 markers included in our liver group are enzymes that initiate or support the many detoxifying, energy producing, and overall housekeeping reactions that keep our bodies functioning.

• ALT = alanine transaminase
• AST = aspartate transaminase
• GGT = gamma-glutamyl transpeptidase

All of the markers are found in large quantities in the liver and can be elevated in the blood when there is liver damage; however, they are also present in other tissues.  While GGT is fairly specific to the Liver, ALT and AST are also found in significant quantity in skeletal muscles. When muscle is damaged, such as in response to exercise, AST and ALT are released from the  muscle and their concentration in the blood increases. In an athletic population, it is understandable that these markers may be elevated on routine blood tests.

ALT and AST can remain elevated for 7 or more days after strenuous exercise. The higher the intensity and the longer the duration of workout will result in higher peak levels and levels remaining high for longer. Untrained athletes will see larger and longer increases relative to more trained athletes.. As an athlete trains, their work capacity increases, allowing them to sustain greater training loads/volumes with a comparable increase in ALT, AST and CK. While resistance training generally causes greater muscle damage than endurance events, high levels of muscle damage can also be inflicted in ultra-endurance races and events, particularly those with larger or numerous changes in elevation. At Insidetracker, we have found that trail runners, road cyclists and mountain bikers are more susceptible to these types of elevations. Creatine Kinase, an enzyme found in our muscles, is another marker of muscle damage that follows the same pattern as AST and ALT after strenuous exercise. Adequate protein intake after strenuous exercise is required to repair the damage.

The general pattern of increases in aspartate transaminase (AST), alanine transaminase (ALT), and Creatine Kinase (CK) in response to muscle damage.

Some added insight

Because we know it can be alarming to have elevated liver markers, we’ve added new paragraphs for the liver group to help you better interpret your results. Now, when you view your liver group, your paragraph will inform you whether or not muscle damage may be skewing the results of your liver enzymes based on your CK.

Monitoring your levels for overtraining

Monitoring the levels of your AST, ALT, and CK throughout training can help you determine if your muscles are recovering as they should be. Prolonged elevations in any of these markers can mean that your training load is high, recovery is taking longer, and the risk of overtraining may be greater. Alongside these biomarkers, Testosterone and cortisol provide additional context into one’s training, particularly the T:C and fT:C ratios as these are often used as a metric of recovery and non-functional over-reaching Testosterone is important for both males and females, as it help to build and repair muscle. Declining levels of testosterone may be a red flag for impaired levels of muscle repair. Similarly, cortisol can be elevated as training continues. As stress related to workout frequency, intensity, and calorie demand increases throughout a season, cortisol levels slowly increase as well. Cortisol uses muscle and fat as substrate to provide a constant source of glucose in case of “emergency”. 

What about GGT?

Unlike AST and ALT, GGT is not found in the muscle (although it is in other tissues). Elevated GGT cannot be attributed to muscle damage—unless the damage is so severe that other organs are being negatively affected. GGT is  a more specific marker of overall liver health. Elevated levels can be caused by alcohol, medications (including chronic Tylenol use), and unhealthy lifestyle. In fact, GGT is associated with all the biomarkers you want to keep in the optimal zone. When looking at our users, elevated GGT is associated with elevated glucose, LDL, hsCRP, and triglycerides and with low HDL and vitamin D.

Some tips for keeping GGT levels within the optimal range:

• Drink alcohol in moderation (1 drink per day for women and 2 drinks per day for men)
• Use over-the-counter pain relief sparingly
• Engage in moderate aerobic activity or HIIT
• Follow a healthy diet within your calorie needs that is high in fiber and low in saturated fat and added sugars
• Maintain a healthy weight

Want to maximize your rest day? Download this FREE checklist to help optimize recovery on your day off.  

Liver Enzyme – an overview

Enzymes

Liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), are the most sensitive indicators of hepatocyte injury. Both AST and ALT are normally present in low concentrations. However, with cellular injury or changes in cell membrane permeability, these enzymes leak into circulation. Of the two, the ALT is the more sensitive and specific test for hepatocyte injury as AST can be also elevated in the state of cardiac arrest or muscle injury. Serum glutamate dehydrogenase (GLDH) is also a marker and is elevated in the state of severe hepatic damage. Serum alkaline phosphatase (ALKP) provides an elevation of the patency of the bile channels at all levels, intrahepatic and extrahepatic. Elevation is demonstrated in patients with obstruction of the extrahepatic biliary tract or caliculi. In general, serum levels are elevated in hepatobiliary disease.¹⁰⁶

As mentioned earlier liver damage occurs after a thermal injury. The elevation of hepatic enzymes correlates with the severity and extend of the hepatic injury. Small hepatic injury leads to a predominantly elevation of the cytoplasmatic enzymes ALT and only little elevation of AST. The so-called de Ritis ratio GOT/GPT <1. In a state of severe hepatic damage, mitochondrial bound enzymes are strongly elevated and the de Ritis ratio GOT/GPT >1 (Table 26.3).¹⁰⁶

Thermal injury causes liver damage by edema formation, hypoperfusion, pro-inflammatory cytokines or other cell death signals with the release of the hepatic enzymes. Others and we have shown that serum AST, ALT and ALKP are elevated between 50 to 200% when compared with normal levels (Figure 26.9). We observed that serum AST and ALT peaked during the first day postburn and ALKP during the second day postburn. During hepatic regeneration all enzymes returned to baseline between 10–14 days postburn. If liver damage persists, enzymes stay elevated. There is no need for therapeutic intervention to decrease elevated enzymes. Enzymes can only be used as markers and the effect of therapeutics can be studied.

Abnormal Liver Function Test Predicts Type 2 Diabetes

A community-based prospective study

Increased activities of liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyltranspeptidase (GGT) are indicators of hepatocellular injury. Increased activity of these markers is associated with insulin resistance (1), metabolic syndrome, and type 2 diabetes (2–9). However, most of these studies were performed in Western countries (2–5,7,9), and the two studies from Japan and Korea were not community based (6,8). In this prospective community-based study, we evaluated the relationships between markers of liver function and the onset of type 2 diabetes after adjusting for potential risk factors including inflammatory markers.

RESEARCH DESIGN AND METHODS—

In 2001, the Korean government funded a large community-based epidemiological survey to investigate the trends in diabetes and the associated risk factors (10). For this study, two communities, one from a rural Ansung and the other from an urban Ansan community, were selected. The baseline examination was performed in 2001–2002, and biennial follow-up examinations will continue through 2010. The age range for eligibility was 40–69 years. Of the 7,192 eligible individuals in Ansung, 5,018 were surveyed (70% response rate) using a cluster sampling method. A total of 15,580 individuals were eligible in Ansan, and we successfully recruited 5,020 (32.4%) using a random sampling method of the local telephone directory. The study protocol was approved by the ethics committee of the Korean Health and Genome Study.

Anthropometric parameters and blood pressure were measured by standard methods. Fasting plasma glucose, lipid profiles, insulin, high-sensitivity C-reactive protein, and the activities of hepatic enzymes were measured in a central laboratory.

All participants except those on oral hypoglycemic medications or insulin therapy underwent a 2-h 75-g oral glucose tolerance test at baseline and at each follow-up visit. Pancreatic β-cell function and insulin resistance were calculated using the homeostasis model assessment (HOMA-β and HOMA-IR, respectively) and quantitative insulin sensitivity check index (QUICKI) (11,12).

All data are presented as means ± SD. Statistical analyses were conducted using t tests, Pearson’s correlation, and logistic regression models by using SPSS (version 12.0; SPSS, Chicago, IL). P < 0.05 was considered significant.

RESULTS—

At baseline, 594 (5.9%) of 10,038 participants were being treated for diabetes and 542 (5.4%) were newly diagnosed with type 2 diabetes by oral glucose tolerance testing. The clinical and biochemical features of men (n = 4,075) and women (n = 4,675) were investigated after excluding those with a known history of diabetes and those positive for hepatitis B or C by antibody testing. Mean ± SD age was 51.4 ± 8.7 and 52.1 ± 8.9 years in men and women, respectively. Regarding alcohol drinking, the proportion of current drinkers in men was much higher than that in women (71. 0 vs. 26.5%, P < 0.01). Mean levels of liver enzyme activities were higher in men than those in women (30.8 ± 20.1 vs. 25.3 ± 13.1 IU/l in AST, 31.0 ± 24.8 vs. 21.4 ± 16.0 IU/l in ALT, and 50.4 ± 30.7 vs. 18.8 ± 20.4 IU/l in GGT, respectively; all P < 0.05).

Of the three liver enzymes, ALT activity correlated better with BMI than AST or GGT (r = 0.203 vs. r = 0.023 or r = 0.016 in men; r = 0.174 vs. r = 0.058 or r = 0.126 in women, respectively). In the correlation with HOMA-IR, ALT showed a stronger relationship than either AST or GGT (r = 0.104 vs. r = 0.044 or r = 0.025 in men; r = 0.082 vs. r = 0.061 or r = 0.074 in women). When divided into drinkers and nondrinkers, a similar pattern was found in both sexes. Accordingly, ALT was used as the marker for liver function in all subsequent analyses.

We stratified participants into quartiles according to ALT activity in each sex. In the percentage of participants who had obesity, bad lipid profiles, and high glucose, insulin and HOMA-IR increased progressively with ALT quartile in both sexes (Table 1). In contrast, increasing quartiles of ALT were associated with declining QUICKI, HOMA-β, and HDL cholesterol concentration after adjusting for age and alcohol status. The percentage of alcohol drinkers increased with ALT only in men.

At the 2-year follow-up, we found that the highest quartile of ALT level was a predictor of the incidence of type 2 diabetes in both sexes (Table 1). We also found similar results when GGT was used, although the relative risk was lower than that for ALT. However, we found no relationships when we used AST.

CONCLUSIONS—

In this study, we found that the highest quartile of ALT activity was associated with risk of type 2 diabetes both cross-sectionally at baseline and prospectively at the 2-year follow-up period, as well as before and after adjusting for alcohol intake. We also demonstrated the independent predictive value of ALT activity on the incidence of type 2 diabetes after controlling for potential risk factors including age, family history, BMI, alcohol intake, and insulin resistance in both sexes. This result supports the previous studies reporting an association between abnormal liver function and type 2 diabetes, conducted mainly in Caucasian populations (2–5,7,9).

The liver is an important site for insulin clearance (13) and production of inflammatory cytokines (4,9). A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue can lead to hepatic steatosis and insulin resistance (5). Other researchers have reported an association between elevated ALT activity and fatty liver (7,14) in obesity, insulin resistance, and type 2 diabetes (1). Another study has shown that ALT activity even within the normal range correlates with increasing hepatic fat infiltration (15). In contrast, elevated AST and GGT activities are not related to hepatic or whole-body insulin sensitivity (4). Although we did not confirm the presence of fatty liver by imaging, we showed a continuous relationship between ALT activity, lipid and glucose concentrations, HOMA-IR, HOMA-β, and QUICKI—all of which were independent predictors of type 2 diabetes.

Elevated liver enzyme activity may also reflect inflammation, which impairs insulin signaling (4). In agreement with other studies (16–18), our data show that individuals in the top ALT quartile have the highest levels of high-sensitivity C-reactive protein, which is also an independent predictor for type 2 diabetes (19).

In conclusion, in this population-based survey, increased activity of liver enzymes, notably ALT, was associated with a twofold increase in the risk of type 2 diabetes independently of conventional risk factors. Because the measurement of ALT activity is internationally standardized and often part of the routine clinical assessment, this marker may serve as a useful marker to identify individuals at high risk of type 2 diabetes in Asian populations.

Table 1—

Clinical and biochemical characteristics of male and female participants, stratified by ALT quartiles, and relative risk (RR) of ALT quartiles in logistic regression models for incidence of diabetes

Acknowledgments

This study was supported by the National Genome Research Institute, Seoul, Korea (2001-347-6111-221, 2002-347-6111-221, 2003-347-6111-221, 2004-347-6111-213, and 2005-347-24002-440-215).

Footnotes

• Published ahead of print at http://care.diabetesjournals.org on 12 July 2007. DOI: 10.2337/dc07-0106.

  A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

  The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

• • highwire.org/Journal” hwp:start=”2007-07-04″>Accepted July 4, 2007.
  • Received January 17, 2007.
• DIABETES CARE

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Liver enzyme tests and others | Guides

Liver enzyme tests: ALT and AST

Liver enzymes are proteins with specific functions (and difficult long names).

If the liver becomes damaged, some of these enzymes leave the liver and enter the blood.

Many things can cause liver enzyme levels to increase. These include:

• Prescription and over-the-counter medicines.
• Herbs, vitamins and supplements.
• Toxic fumes.
• High alcohol intake or coming off drugs and/or alcohol.
• New or existing hepatitis infection.

HIV drugs can cause liver enzymes to increase, though usually not to dangerous levels. In some cases, these drugs need to be stopped or switched.

People taking HIV drugs (or other drugs processed by the liver) need to have liver enzymes routinely measured with other blood tests. This is especially important with HCV coinfection.

Raised liver enzymes do not always mean there is liver damage. But persistently high levels can be a sign of ongoing damage that needs to be treated.

ALT and AST

Two important enzymes are ALT (alanine aminotransferase) and AST (aspartate aminotransferase).

ALT is produced in the liver and Increases are usually a sign of liver inflammation or damage. However, ALT is not a good marker of either liver damage or changes in liver health. This is because HCV itself causes levels to go up and down.

Up to a third of people with chronic HCV always have a normal ALT, even with serious liver damage.

If an increase in ALT continues to rise, or is getting worse, it may mean continued HCV related inflammation which may eventually lead to scarring (fibrosis).

AST is an enzyme that is made in the heart, intestines, and muscles. AST is only used to monitor liver inflammation and damage in combination with other tests.

• Normal liver enzymes, even over time, do not mean there is no liver damage.
• Raised liver enzymes do not always mean there is liver damage, but if they are persistently high this can be a sign of ongoing damage, and that treatment may be a good idea.

ALP, GGT, bilirubin, albumin and prothrombin time

Routine monitoring in coinfection also includes ALP, GGT, bilirubin, albumin and prothombin time (PT).

ALP (alkaline phosphatase) is an enzyme that is present throughout the body, including the liver. If blood levels of ALP increase, this can be a sign of tissue disease or damage. Your doctor can also test specifically for ALP from the liver. Some medications, including the HIV protease inhibitor atazanavir, can increase ALP. Elevated ALP from the liver is a sign of blocked bile ducts caused by liver disease.

GGT (gamma glutamyl transferase) is an enzyme involved in metabolism that is produced in the bile ducts. Any liver disease, heavy drinking, and some medications can all increase GGT.

Bilirubin is a waste product from the breakdown of red blood cells. Before it passes through the liver, where it is mixed with sugars to become water-soluble, it is called indirect or unconjugated bilirubin. Once it has been processed through the liver it is called direct or conjugated bilirubin.

A damaged liver may be unable to process bilirubin, causing an increase in the total bilirubin levels. Usually, a laboratory will subtract the amount of direct bilirubin from the total amount of bilirubin in the bloodstream; the leftover is indirect bilirubin.

Jaundice is an increased level of bilirubin and common signs include a yellowing of the skin and eyes, dark urine or pale stools. Some drugs, including the HIV protease inhibitor atazanavir, and HCV protease inhibitors, can increase bilirubin.

Albumin is a protein made by the liver. It carries drugs, hormones and waste products through the blood and maintains fluid levels within the body. An abnormally low level of albumin is a sign of serious liver damage.

Last updated: 17 August 2017.

Canine liver enzymes-so many questions!

ALT, easy as 123 … or maybe not! (Photo: Shutterstock.com)As you all too readily know, increased serum liver enzyme activities are common in dogs and are, quite often, a diagnostic challenge. In a recent Fetch dvm360 session, Jonathan Lidbury, BVMS, MRCVS, PhD, DACVIM, DECVIM, said “Increased liver enzymes are a big cause of consternation and confusion among all of us. We have to deal with them all of the time. They’re one of the most common laboratory abnormalities of all.”

Sometimes increased serum liver enzyme activities occur because the patient does have primary hepatobiliary disease, but sometimes they are secondary to extrahepatic disease. And to confound results even more, tissues other than the liver also produce these enzymes. The liver plays a major role in the metabolism and excretion of drugs and exogenous and endogenous toxins, so it’s susceptible to injury from toxins and from diseases in other parts of the body. Plus, increased liver enzyme activities can occur from benign processes (e.g. hepatic nodular hyperplasia) or from conditions that are progressive and require early intervention for the best outcome (e.g. chronic hepatitis).

Performing extensive diagnostic evaluation, including liver biopsy, is costly and clients may be either reluctant or unable to proceed. It can be difficult to know how aggressively to work up these dogs. Dr. Lidbury says that if the cause of the elevated activity is a primary liver disease like chronic hepatitis or a liver tumor, the workup can escalate up to the need to perform a liver biopsy fairly quickly. Contrast that with extrahepatic causes. “Sometimes, especially for mild elevations in alkaline phosphatase (ALP), benign neglect may be the best course of action,” he says.

Through a logical, step-by-step approach, you can assess which dogs should be investigated for extrahepatic disease, which cases may need a liver biopsy, and which cases can be managed less aggressively.

Should I be checking ALT? AST? ALP? GGT?

Yes … but you should also know the enzymology behind all of these markers-where and why they’re produced-so you know how to interpret the laboratory results. “There are two big categories,” says Dr. Lidbury. “First, we have markers of hepatocellular damage. That would include alanine aminotransferase (ALT) and aspartate aminotransferase (AST). And then we have markers of cholestasis, ALP and gamma-glutamyltransferase (GGT). ”

ALT

ALT is found primarily in the cytosol of hepatocytes. It’s released with increased cell membrane permeability or cell death. “Of all the liver enzymes, ALT is the most liver-specific,” says Dr. Lidbury. On rare occasions, ALT activity can be increased in patients with severe muscle injury. But, in general, ALT is considered a sensitive and specific marker of liver injury. “When hepatocytes die, then you get leakage,” Dr. Lidbury says. “ALT can also leak when you have just cell membrane damage. You don’t have to have necrosis for ALT to go up. Also, severe ALT increases don’t necessarily mean you have irreversible disease. Sometimes we misinterpret really high ALTs as irreversible disease and a poor prognosis. If you have a dog with acute liver injury, it might have a sky-high ALT, but if you can support the dog through that initial injury, then the disease could be reversible, and the liver can get back to normal. The liver has such great regenerative capacity. ”

AST

In dogs, aspartate aminotransferase (AST) is found in both the mitochondria and cytosol of hepatocytes. (In human hepatocytes, AST is mainly found in the mitochondria, and so, in people, it is a marker of severe liver damage.) The cytosolic fraction is released with increased cell membrane permeability or cell death, whereas the mitochondrial fraction is released only when there is hepatocyte necrosis. In general, increases in AST parallel those in ALT, but muscle disease can increase serum AST activity. Because of this, AST is considered to be less liver-specific than ALT. “At Texas A&M, we have actually taken AST off our basic chemistry panel because we feel it doesn’t add much information,” says Dr. Lidbury. A lot of the bigger reference labs still have it on their panels. It’s not un-useful; it usually just parallels the ALT.”

ALP

“So next we have that problem child-the ALP,” says Dr. Lidbury. “This is probably the least liver-specific and also the most commonly elevated liver enzyme. That is why it causes problems.” As you probably remember from pathophysiology units in veterinary school, there are different forms of ALP-hepatic, bone, renal, intestinal and steroid-induced ALP isoenzymes. They all may contribute to serum ALP activity in dogs. Dr. Lidbury says, however, “Luckily, when we measure ALP, we don’t have to worry about all of the isoforms because some of them aren’t actually measured by the assay. They have a trivial contribution to the overall activity of ALP in the serum, which is what the assay measures.” In the liver, ALP is bound to the membranes of the hepatocytes that form the bile canaliculi and the sinusoidal membranes. In cholestasis, the membrane-bound ALP is released into circulation and the synthesis of this enzyme is induced. ALP is considered a sensitive marker of cholestasis in dogs, but because of the other isoenzymes, ALP is not liver-specific.

“I don’t tend to take ALP quite as seriously as increases in ALT,” Dr. Lidbury says. “Sometimes they’re not actually that clinically significant, if they’re mild and the dog doesn’t have other signs going on. Sometimes this is a case where benign neglect may be the best course of action, but not always. Obviously, if ALP didn’t tell us anything, we wouldn’t measure it. There is a nuance; it depends on looking at the whole case.”

So, what can cause increased ALP activity? Dr. Lidbury answers, “If you look in textbooks, there’s a long list with about 30 to 40 reasons. But in terms of big categories, causes of increased ALP can be hepatic disease such as nodular hyperplasia (a very common, completely benign cause of increased ALP in older dogs), vacuolar hepatopathy (common with Cushing’s disease), toxins, chronic hepatitis, neoplasia, biliary tract disease (such as a gallbladder mucocele) and extrahepatic disease (such as pancreatitis).”

Serum ALP activities can be increased when there is increased osteoblast activity, such as in growing dogs, or when the dog has an osteolytic disease, such as osteosarcoma. The steroid-induced ALP isoenzyme can be induced by both exogenous and endogenous glucocorticoids. Dr. Lidbury warns, “Steroid-induced isoenzyme is really important because it can be iatrogenic. Asking the owner whether the dog is on any steroids or whether they’re using any steroid hand creams themselves, that kind of thing, is very important.”

GGT

Gamma-glutamyltransferase (GGT) is bound to the hepatocytes in the bile canaliculi and bile ducts. Increases in serum GGT activity generally parallel those in ALP. Both GGT and ALP are considered sensitive markers of cholestasis. Dr. Lidbury says, however, “GGT can’t differentiate between intrahepatic and extrahepatic cholestasis. You’d think since it’s a bit further down the biliary tract, that it might. But, unfortunately, it doesn’t do that.” In general, increases in GGT are considered to be less sensitive but more specific for the presence of hepatobiliary disease than those of ALP.

The pattern of liver enzymes

Dr. Lidbury confirms that looking at patterns of liver enzymes can be useful (Table 1). “For example, if you have a dog where your ALP is 10X the upper limits of normal and your ALT is increased to twice the upper limits of normal, we’d say that dog has a cholestatic pattern,” he says. “So, we’d be thinking about diseases that cause intra- or extra-hepatic cholestasis. If you have the opposite situation, and a dog has an ALT that is 10X the upper limits of normal and the ALP is only very modestly increased, then that’s more of a hepatocellular damage pattern. That makes you think of things like chronic hepatitis or toxins. Sometimes you get genuinely mixed patterns, and you can’t differentiate the two. But you can often get some clues.”

Table 1: Typical patterns of clinicopathological changes associated with liver disease in dogs

Laboratory test

Acute hepatitis/hepatic necrosis

 Chronic hepatitis

Cirrhosis

Congenital portosystemic shunt

Biliary tract obstruction

Non-obstructive biliary tract disease

Hepatic neoplasia

ALT

^^ – ^^^

^ – ^^^

N – ^^

N – ^

N – ^^

N – ^^

N – ^^

ALP

^ – ^^

^ – ^^

N – ^^

N – ^

^^^

^ – ^^^

N – ^^

Total bilirubin

N – ^^^

N – ^^

N – ^^^

N

^^ – ^^^

N

N – ^

Preprandial SBA

N – ^^

N – ^^

^ – ^^^

N – ^^

^^ – ^^^

N

N – ^

Postprandial SBA

N – ^^

N – ^^

^ – ^^^

^^ – ^^^

^^ – ^^^

N

N – ^

Ammonia

N – ^^

N – ^^

N – ^^

^ – ^^^

N

N

N – ^

Key

ALT-serum alanine transaminase activity

ALP-serum alkaline phosphatase activity

SBA-serum bile acid concentration

N-within the reference interval

^-mild increase

^^-moderate increase

^^^-severe increase

What can the patient history and exam tell me?

Since there are so many causes of increased liver enzyme activities, Dr. Lidbury says the key is to narrow the list of all possible causes down to those that are probable for a patient on that day. The patient history and physical examination are often helpful in doing this. The patient’s signalment can help refine the differential diagnosis list. See Table 2 for known age and breed predispositions for certain liver conditions.

Table 2. Signalment to refine the differential diagnosis list for hepatic injury

Age

Very young dogs are more likely to suffer from congenital conditions (e.g. congenital portosystemic shunts) or infectious diseases (e.g. infectious hepatitis), rather than neoplasia or inflammatory conditions, such as chronic hepatitis.

Copper-associated chronic hepatitis

Bedlington terriers

Skye terriers

West Highland white terriers

Dalmatians

Labrador retrievers

Idiopathic chronic hepatitis

Doberman pinchers

Cocker spaniels

Congenital portosystemic shunts

Maltese terriers

Yorkshire terriers

Havanese terriers

Pugs

Miniature schnauzers

When taking a patient’s history, be sure to ask the client specifically about exposure to hepatotoxins such as cycads (including the sago palm), blue green algae, Amanita mushrooms, aflatoxins, heavy metals, xylitol or chlorinated compounds. Drugs that can be hepatotoxic include ketoconazole, azathioprine, carprofen, lomustine, acetaminophen, mitotane, phenobarbital and various antimicrobial agents.

“Asking specifically about nutraceutical and herbal remedies is important, especially in this situation, because there are quite a few herbal remedies that are known to have the potential to cause liver injury in dogs,” Dr. Lidbury says. Those include herbal teas, pennyroyal oil and comfrey.

Checking the dog’s vaccination history is also important because leptospirosis and canine adenovirus-1 can cause hepatic injury.

Early in the course of liver disease, a dog may not have any or nonspecific findings or clinical signs such as vomiting, diarrhea, weight loss, polyuria/polydipsia and hyporexia. Dr. Lidbury admits that these are not very helpful signs since so many different diseases can cause them. “But certainly, if you have a dog with increased liver enzymes and that kind of clinical sign, then that may make you a little more aggressive about how you approach that dog,” he says. He says it’s also important to remember that dogs with hepatobiliary disease don’t always display clinical signs or have abnormal physical examination findings.

Certain exam findings suggest an extrahepatic disease is causing increased liver enzyme activities. For example, polyphagia is consistent with diabetes mellitus or hyperadrenocorticism and bilateral symmetric alopecia is consistent with hypothyroidism or hyperadrenocorticism. Physical examination findings consistent with hepatobiliary disease include icterus, ascites, poor body condition, stunted growth, hepatomegaly or signs of hepatic encephalopathy. When any of these clinical signs are present, you will want to investigate further.

What clues can other lab tests provide?

Other changes on a serum chemistry profile can provide clues about the cause of increased serum liver enzyme activities. “You can look for signs of liver dysfunction,” Dr. Lidbury says. “Things the liver produces-albumin, cholesterol, glucose, and blood urea nitrogen (BUN)-can be decreased with liver disease or decreased hepatic function. And bilirubin can be increased.”

Dr. Lidbury warns, “It’s definitely possible to have serious liver disease and have all of those things completely normal. The liver has this large reserve capacity. That’s a really good thing for the body, but it makes our life a bit harder when we’re trying to diagnose liver disease.” It’s important to remember that these changes are not specific for hepatobiliary disease. For example, the serum bilirubin concentration may also be increased when there is hemolysis.

Dr. Lidbury offers this helpful tip: “When we look at a chemistry panel, especially when we’re in a rush on a busy day in the clinic, we tend to look for things that are flagged. You go down the list of 10 to 15 analytes and look for things that are high or low. You can miss things doing that. Some of these numbers are in the normal range, but at the low end of normal. If several things are like that, it can give you an impression that the liver is not working so well. So, try to slow yourself down and actually look at the numbers. Really read them.”

Patterns of serum liver enzyme activities can suggest certain pathologies. For example, during cholestasis, ALP activity is dramatically increased and is higher than ALT activity. There may also be evidence of extrahepatic diseases. A complete blood count (CBC) can suggest inflammatory disease or rule out hemolysis. If the CBC shows microcytosis, that’s consistent with portosystemic shunting (or iron deficiency).

Dr. Lidbury also recommends conducting a urinalysis (UA). “Usually you can justify doing a UA whenever doing a chemistry panel. It just allows you to fully interpret that chemistry panel.” He notes that urine specific gravity can be decreased in patients with hepatic insufficiency or portosystemic shunts. Excessive bilirubinuria in dogs implies hemolytic or hepatobiliary disease. Urate urolithiasis seems to be more common in patients with portosystemic shunts than those with other types of hepatic dysfunction, but urate crystalluria is not specific for hepatobiliary disease.

When should I do more testing?

Once you have completed a basic evaluation of a dog, you have to decide whether to pursue further diagnostic testing. “It’s hard to make hard and fast rules about when you should take things further. Every case is different,” says Dr. Lidbury. “So what I offer are more guidelines than rules.”

Dr. Lidbury’s guidelines:

If clinical findings or other laboratory test results suggest primary hepatobiliary disease, pursue further diagnostic testing.

If clinical findings or laboratory test results suggest extrahepatic diseases are the cause of increased liver enzyme activities, further diagnostic evaluation to identify the underlying disease is needed.

If serum liver enzyme activities (ALP or ALT) are severely (three times the upper limit of the reference range) or persistently increased (greater than twice the upper limit of the reference range for more than three to four weeks), further diagnostic evaluation is needed.

Because ALT is more liver-specific than ALP, increases in serum ALT activity are more concerning or worrisome than increases in ALP.

If none of these conditions apply, then it is reasonable to wait and recheck the serum liver enzymes later.

What comes after a chemistry panel, CBC and UA?

Dr. Lidbury’s advice: “Next we may want to do some bile acid tests. Ammonia has some utility, but it’s more limited and not every practice has the capability to measure ammonia. It seems to be affected a bit more by other variables, too.” He says that measurement of plasma ammonia and paired preprandial/postprandial bile acids are sensitive tests for portosystemic shunting, and he recommends performing one of these tests when a portosystemic shunt is suspected. Because of the hepatic functional reserve capacity, these tests are not as sensitive in detecting hepatic insufficiency (in the absence of shunting). “Remember that dogs can have these normal liver function tests and still have significant liver disease,” Dr. Lidbury says. Also, performing these tests does not always change the decision about whether to perform a liver biopsy.

Imaging

Radiography. “Plain radiographs are useful for things like assessing the general size and shape of the liver,” says Dr. Lidbury. “You can perhaps see masses or maybe extrahepatic disease, like a foreign body in the GI tract. But radiographs rarely lead to a definitive diagnosis of liver disease.”

Abdominal ultrasonography. This form of imaging is more useful than radiography for evaluating the hepatic parenchyma and the biliary tract. “The biliary tract is quite a hard area to image. Sometimes you’ll get a definitive diagnosis, like a gallbladder with a typical ‘sliced kiwi fruit’ appearance of a gallbladder mucocele,” says Dr. Lidbury. “But sometimes ultrasound doesn’t give us a definitive diagnosis. We may see nonspecific changes like an enlarged liver or a small liver with a slightly abnormal echo texture. You may also have a very boring, completely normal ultrasound and still have chronic hepatitis going on. A normal ultrasound doesn’t rule out severe liver disease. That’s important to bear in mind.” Unless a disease leads to architectural changes in the hepatobiliary system, a definitive diagnosis can’t be made with ultrasonography. Despite this limitation, Dr. Lidbury says that when primary hepatic disease is suspected, abdominal ultrasonography is usually performed before liver biopsy.

Scintigraphy. Dr. Lidbury says scintigraphy is being used less frequently-they rarely use the technique at Texas A&M. “It involves injecting a radioactive isotope, which is why people didn’t like to do it. It’s a very good test for portosystemic shunting. But it doesn’t tell you whether the shunt is intrahepatic or extrahepatic.”

CT and MRI. Dr. Lidbury says that cross-sectional imaging is being used more often for assessing abdominal disease in dogs. Computed tomography (CT) is used most often because it’s quick and a bit cheaper than magnetic resonance imaging (MRI). “Obviously not everybody is going to be able to do this at the moment. But who knows? Maybe in 20 years, every practice will have a micro-CT scanner rather than an x-ray unit,” ponders Dr. Lidbury. “It’s a nice way to look for congenital portosystemic shunts. And it’s quite good if you’ve got a big liver mass. Surgeons like to look at these CTs before they decide if they will try to resect a mass or not.”

Cytology

“Cytology-this can definitely be useful. But I don’t do it in every case,” says Dr. Lidbury. “I pick my cases. It’s relatively easy to do. You just need ultrasound guidance. It’s pretty safe and quite cheap, too.” Hepatic cytology can lead to a definitive diagnosis of certain diseases, such as lymphoma, and can be highly suggestive for the presence of others. You may wish to perform cytology when you suspect a round cell tumor is present, when you suspect infectious agents (e.g. Histoplasma capsulatum) and when hepatic masses are visible with ultrasonography. “Cytology allows us to look at the cells, but it doesn’t allow us to see how those cells are actually arranged in their architecture. Because of that, there are some conditions-like chronic hepatitis-that you can’t diagnose cytologically.”

When should I biopsy the liver?

To make a definitive diagnosis of primary hepatic disease, a liver biopsy is often required. “This is kind of the last step in the diagnostic workup,” says Dr. Lidbury. “It’s quite an invasive and expensive technique.” Click here (or on the image) to download a flowchart showing how Dr. Lidbury suggests approaching the decision about whether to perform a liver biopsy on a particular patient.

Before doing a biopsy, Dr. Lidbury recommends assessing the dog’s risk of hemorrhage by measuring prothrombin and activated partial thromboplastin time, ideally measuring serum fibrinogen concentration, and performing a platelet count. He also usually does a buccal mucosal bleeding time.

The three types of liver biopsy techniques in dogs are percutaneous needle biopsy, laparoscopic biopsy and surgical biopsy. Each technique has advantages and disadvantages. See Table 3 for a comparison of the three techniques. Dr. Lidbury says, “All of them are valid ways to get liver biopsies. It just depends on what you have available and how comfortable you feel. Sometimes it’s a bit about the patient, too.”

Table 3. A comparison of liver biopsy techniques

Percutaneous needle biopsy

Laparoscopic biopsy

Surgical biopsy

Invasiveness

Least

Intermediate

Most

Expense

Least ($)

Intermediate ($$)

Most ($$$)

Size of biopsy specimen

Smallest

Intermediate

Largest

Hospitalization or postoperative care required?

No hospitalization required

Patient is usually discharged same day

Patient may need to be hospitalized; incision requires postoperative care

Bleeding risk

Highest

Low

Low

Ability to control hemorrhage

Least ability to control; if bleeding occurs, may need to perform exploratory surgery to control

Can apply pressure or gel foam to area of hemorrhage through laparoscopic incisions

Direct visualization allows surgeon to control bleeding

Other disadvantages?

Special equipment required, which translates to increased cost for client

Other advantages?

Visualization of liver and surrounding area is best of three techniques; simple procedure to perform

No matter which technique is chosen, it’s important to collect multiple biopsy samples. Dr. Lidbury advises, “I’d keep part of the biopsy specimens back for aerobic and anaerobic culture and copper quantification. When you get the pathology report back and it says there are bacteria, or they suspect it’s copper, you’re going to regret it if you have thrown everything into formalin.”

“Again, it is hard to make universal rules about when to perform a liver biopsy, because every case is different,” he says. But when you suspect primary hepatic disease, he advises that it’s better to go ahead and do the biopsy rather than delay until the dog is in end-stage liver failure, at which point treatment will probably be ineffective.

Suggested reading

> Alvarez L, Whittemore J. Liver enzyme elevations in dogs: diagnostic approach. Compend Contin Educ Vet 2009;31(9):416-418.

> Cooper J, Webster CL. The diagnostic approach to asymptomatic dogs with elevated liver enzyme activities. Vet Med 2006:101(5):279-284.

> Lidbury JA, Steiner JM. Diagnostic evaluation of the liver. In: Canine & feline gastroenterology. 1st ed. St. Louis: Elsevier Saunders, 2013;863-875.

About the speaker: Jonathan Lidbury, BVMS, MRCVS, PhD, DACVIM, DECVIM, is an assistant professor in the Department of Veterinary Small Animal Clinical Sciences at Texas A&M University in College Station, Texas. He is interested in all areas of small animal gastroenterology and is working to develop new noninvasive tests for liver disease in dogs.

Strong link found between abnormal liver tests and poor COVID-19 outcomes

Researchers at the Yale Liver Center found that patients with COVID-19 presented with abnormal liver tests at much higher rates than suggested by earlier studies. They also discovered that higher levels of liver enzymes — proteins released when the liver is damaged — were associated with poorer outcomes for these patients, including ICU admission, mechanical ventilation, and death.

The study appeared online on July 29 in Hepatology. 

Previous studies in China found that approximately 15% of patients with COVID-19 had abnormal liver tests. The Yale study, which looked retrospectively at 1,827 COVID-19 patients who were hospitalized in the Yale New Haven Health system between March and April, found that the incidence of abnormal liver tests was much higher — between 41.6% and 83.4% of patients, depending on the specific test.

In all, the Yale researchers examined five liver tests, looking at factors such as elevations in aspartate aminotransferase (AST) and alanine transaminase (ALT), which indicate liver cell inflammation; an increase in bilirubin, which indicates liver dysfunction; and increased levels of alkaline phosphatase (ALP), which may indicate inflammation of bile ducts. 

Although the researchers do not know why the incidence of abnormal liver tests was so much higher than in previous studies from China, senior author Dr. Joseph Lim, professor of medicine and director of the Yale Viral Hepatitis Program, said other health differences between the Chinese and U.S. populations could account for it. 

“We can speculate that U.S. patients may have an increased rate of other risk factors such as alcoholic or non-alcoholic fatty liver disease,” he said.

In the U.S., close to one-third of people have fatty liver disease, and several million people have chronic hepatitis B or C.

Dr. Michael Nathanson

Liver disease is widespread in the U.S. population. Dr. Michael Nathanson, the Gladys Phillips Crofoot Professor of Medicine (digestive diseases), professor of cell biology, director of the Yale Liver Center, and a co-author of the study, said: “In the U.S., close to one-third of people have fatty liver disease, and several million people have chronic hepatitis B or C.” 

Because the Yale researchers had access to patients’ health records, they were also able to look at their liver tests prior to being diagnosed with COVID-19. Approximately one-quarter of patients in the study had abnormal liver tests prior to being admitted for the virus. But regardless of whether patients came to the hospital with existing liver problems or developed them during their COVID-19-related hospitalization, a strong association was observed between abnormal liver tests and the severity of the COVID-19 cases, the researchers said.  

Rather than the liver itself driving poorer outcomes in COVID-19 patients, the organ is more likely “a bystander” affected by the hyperinflammation associated with COVID-19 and by the side effects of related treatments, Nathanson said.

The study noted a relationship between drugs used to treat severe COVID-19 and liver damage, most significantly the drug tocilizumab.

“We observed a strong association between the use of COVID-19 medications and abnormal liver tests,” said Lim, but added that they could not confidently tease out that the abnormal tests were due to “drug-induced liver injury” as opposed to the disease. 

The researchers have additional clinical and lab-based studies underway to further understand COVID-19’s impact on liver pathology. Nathanson noted that as one of only four National Institutes of Health-sponsored liver centers in the country, the Yale Liver Center is uniquely positioned to advance this research.  

Additional Yale researchers involved in the study include lead author and internal medicine resident Dr. Melanie Hundt; biostatistician Yanhong Deng, co-director of analytics at the Yale Center for Analytical Sciences; and Maria Ciarleglio, associate professor at the Yale School of Public Health.

90,000 Increase in ALT and AST in liver diseases

Alanine aminotransferase (ALT)

The study of the activity of ALT and AST in the blood serum is extremely important for the diagnosis of liver diseases. The increase in their activity is directly proportional to the degree of liver tissue necrosis.

The serum ALT activity is the first and most significant change in liver disease.An increase in ALT activity by 1.5-5 times compared to the upper limit of the norm is considered as moderate hyperenzymemia, 6-10 times as moderate hyperenzymemia and more than 10 times as high. The degree of elevation of ALT activity indicates the severity of liver cell necrosis, but does not directly indicate the depth of violations of the liver functions proper.

In acute hepatitis, regardless of its etiology, ALT activity increases in all patients. At the same time, the ALT level rises 10-15 days before the onset of jaundice in viral hepatitis A, and for many weeks – in viral hepatitis B.In the typical course of acute viral hepatitis, ALT activity reaches its maximum at the 2-3rd week of the disease. With a favorable course, the ALT level is normalized after 30-40 days. Typically, in acute viral hepatitis, the level of ALT activity ranges from 500 to 3000 IU / L.

A repeated and progressive increase in ALT activity indicates a new necrosis of liver cells or a relapse of the disease. Prolongation of the period of increased ALT activity is often an unfavorable sign, as it may indicate the transition of acute to chronic hepatitis.

In acute alcoholic hepatitis, AST activity is higher than ALT, but the activity of both enzymes does not exceed 500-600 IU / L.

Chronic hepatitis is characterized by moderate to moderate hyperenzymemia. In latent forms of liver cirrhosis, an increase in ALT activity may not be observed.

In patients with toxic hepatitis, infectious mononucleosis, intrahepatic cholestasis, cirrhosis, liver metastases, AST activity is higher than ALT.

An increase in ALT activity can also be detected in carriers of the surface antigen of hepatitis B that do not have clinical manifestations, which indicates the presence of outwardly asymptomatic active processes in the liver.

Aspartate aminotransferase (AST)

AST also rises in acute hepatitis and other severe lesions of hepatocytes. A moderate increase is observed in obstructive jaundice, in patients with liver metastases and cirrhosis. De Ritis coefficient, i.e.That is, the ALT / AST ratio, normally equal to 1.33, is lower than this value in liver disease, and higher in heart disease.

In case of an increase in the activity of ALT and AST, we recommend that you sign up for a consultation with a hepatologist and undergo a liver examination using the Fibroscan apparatus – Liver elastometry / elastography

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ALT (ALT, Alanine aminotransferase, alanine transaminase, SGPT, Alanine aminotransferase)

IMPORTANT!

The information in this section cannot be used for self-diagnosis and self-medication.In case of pain or other exacerbation of the disease, diagnostic tests should be prescribed only by the attending physician. For a diagnosis and correct treatment prescription, you should contact your doctor.

We remind you that independent interpretation of the results is unacceptable, the information below is for reference only.

ALT (ALT, Alanine aminotransferase, alanine transaminase): indications for the appointment, the rules for preparing for the test, interpretation of the results and normal indicators.

Indications for prescribing a study

Alanine aminotransferase is an intracellular enzyme, the content of which in the blood of healthy people is low. It is mainly found in the cells of the liver, myocardium, skeletal muscles, and pancreas. When cells containing ALT are damaged or destroyed, the enzyme is released into the bloodstream, and its concentration in the blood increases.

Determination of the level of alanine aminotransferase is carried out for the diagnosis of liver diseases and dynamic monitoring of their treatment.The analysis is performed on suspicion of acute or chronic hepatitis of viral or toxic etiology, cirrhosis of the liver, primary tumors or metastatic liver disease.

The growth of alanine aminotransferase in the blood during hepatitis is noted much earlier than the onset of the icteric stage, which makes it possible to identify pathology at the initial stage.

As part of a screening examination (preventive examination of persons who do not have complaints) to assess the state of the liver, before a planned hospitalization and surgical treatment, an ALT test is prescribed together with another enzyme – AsAT (aspartate aminotransferase).

The level of ALT together with other enzymes is assessed in diseases of the pancreas and gallbladder – pancreatitis, cholecystitis, cholelithiasis; in the presence of complaints of unexplained general weakness, rapid fatigue, yellowness of the skin and sclera, abdominal pain, including a feeling of heaviness in the right hypochondrium, nausea, vomiting.

In addition, the level of ALT is taken into account in myocardial infarction and myocarditis, although in cases of heart damage it is only of secondary importance.The study is prescribed for suspected myositis, muscular dystrophy, when complaints of muscle pain cannot be explained by trauma or excessive physical exertion.

Donation is an obligatory reason for passing the test for ALAT.

ALT values ​​are assessed for any chronic diseases, before prescribing drug therapy, for example, anticancer, anti-tuberculosis drugs, to assess the initial state of the liver and in dynamics to assess the tolerability of drugs.

Preparation for procedure

It is better to take the test in the morning on an empty stomach (after an 8-14 hour break after the last meal).

Drinking water is allowed.

If necessary, it is permissible to donate blood 4-6 hours after a light meal.

The day before, it is advisable to avoid physical and emotional overload, overeating.

5-6 days before the test, exclude alcohol intake.

Avoid smoking for 30 minutes before taking blood.

Deadline

The research is carried out within one working day.

What can influence the results

Intense physical activity the day before and even a few days before the test can lead to damage to muscle tissue (the so-called muscle fiber tear) and, accordingly, an increase in the level of ALT. For the same reason, the analysis given after the injury is not informative.

Taking alcohol, certain medicines (antibiotics, non-steroidal anti-inflammatory, antineoplastic drugs, oral contraceptives, etc.)) often distort the research result. The list of medications to be taken should be discussed with the doctor who ordered the analysis, and those that are possible should be canceled without risk to health.

ALT (ALT, Alanine aminotransferase, alanine transaminase)

For research, blood is taken from a vein. Usually, AST (AST, Aspartate Aminotransferase) is simultaneously determined and the AST / AlAT ratio (de Ritis coefficient) is assessed.

You can take a blood test for ALT (ALT, Alanine aminotransferase, alanine transaminase) at the nearest medical office of INVITRO.The list of offices where biomaterial is accepted for laboratory research is presented in the “Addresses” section.

Interpretation of test results contains information for the treating physician and does not constitute a diagnosis. The information in this section cannot be used for self-diagnosis and self-medication. An accurate diagnosis is made by a doctor using both the results of this examination and the necessary information from other sources: anamnesis, results of other examinations, etc.

Normal values ​​

Units of measurement: Unit / l.

Reference values ​​

Interpretation of indicators

The ALT level depends on the age and gender of the patient.Minor deviations from the norm, as a rule, do not require drug therapy, and related recommendations, such as a balanced diet, avoiding alcohol, etc. should be discussed with your doctor.

The ratio of AsAT / ALAT (de Ritis coefficient) is normally from 0.91 to 1.75.

What do the lowered figures mean?

A significant decrease in the level of ALT can be detected in severe liver damage, for example, at the terminal stage of liver cirrhosis, when the number of liver cells is significantly reduced.

What do the increased numbers mean?

First of all, with an increase in ALT, liver problems should be suspected: fatty hepatosis, hepatitis of viral or toxic etiology, cirrhosis of the liver, liver cancer – primary or metastatic.

The degree of increase in ALT is usually associated with the volume or severity of liver damage, but cannot be considered as a determining factor for the prognosis of the disease. The maximum levels of ALT (and AST) – more than a hundred times higher than the norm, are observed in patients with acute viral and drug hepatitis.

A significant increase in alanine aminotransferase can be observed in acute cholecystitis, gallstone disease, in acute destructive pancreatitis. Another reason may be taking hepatotoxic drugs that damage liver cells.

An increase in the level of ALT is detected with extensive injuries of skeletal muscles, severe myositis and muscular dystrophy, frequent intramuscular injections.

A less significant increase in ALT is recorded in acute myocardial infarction and myocarditis.

Additional examination when the indicator deviates from the norm

If a change (more often an increase) in the level of ALT is detected, patients are consulted
general practitioners,
gastroenterologists, hepatologists, infectious disease specialists.

To clarify the diagnosis, in addition to ALT, other liver enzymes (AsAT, gamma-HT, alkaline phosphatase, bilirubin), clinical blood parameters are usually examined and markers of viral hepatitis, primarily hepatitis B and hepatitis C, are determined.

An ultrasound examination of the abdominal organs is performed, if indicated – computed tomography (CT) with contrast.
If skeletal muscle damage is suspected, the CPK enzyme is additionally examined and a rheumatologist is consulted.

If the heart muscle is suspected, consultation with a cardiologist is required. Usually the doctor prescribes additional electrocardiography (ECG), echocardiography, blood test for MV-CPK, troponin I.

Sources:

1. Shipovskaya A.A., Lutokhina A.A., Larina N.A., Dudanova O .P. The role of new reference values ​​of alanine aminotransferase in the diagnosis of various forms of non-alcoholic fatty liver disease in patients with metabolic syndrome.Journal of Biomedical Technologies No. 1. 2015. S. 9-15.

IMPORTANT!

The information in this section cannot be used for self-diagnosis and self-medication. In case of pain or other exacerbation of the disease, diagnostic tests should be prescribed only by the attending physician. For a diagnosis and correct treatment prescription, you should contact your doctor.

Information checked by expert

Lishova Ekaterina Alexandrovna

Higher medical education, work experience – 19 years

Alanine aminotransferase (ALT)

index

Blood test for ALT indicators in Moscow and the region with a visit to the house

2017
ALT
ALT
KDL
KDL Group of Companies

Alanine aminotransferase (ALT) is an intracellular enzyme from the group of transaminases found in all cells of the body, mainly in the liver in the kidneys, to a lesser extent in the myocardium and skeletal muscles.Usually, a small fraction of ALT circulates in the blood, and an increase in the concentration of this enzyme is observed with any damage to cells – cytolysis, which is accompanied by an increased release of this enzyme into the blood. A blood test for ALT content (usually together with another AST enzyme) is used in the diagnosis of liver diseases, hepatitis of various origins, less often if there is a suspicion of damage to the heart muscle (for example, with myocardial infarction).

ALT and AST are very informative indicators, since their level in liver pathology can increase even before the manifestation of clinical symptoms.Timely detection of an increase in ALT and AST in the blood allows you to diagnose a pathological condition earlier and start treatment.

When an ALT test is prescribed

A biochemical blood test for ALT is recommended for anyone who wants to check the condition of the liver. It is also prescribed for symptoms such as weakness, loss of appetite, nausea, itching, yellowness of the sclera and skin, in the diagnosis of hepatitis. An increase in transaminases (ALT and AST) is possible in febrile conditions, acute infectious diseases with a rise in temperature.The doctor should interpret the results of the analysis taking into account the clinical picture.

You can take a blood test for ALT in the network of clinical diagnostic laboratories KDL, you can do this both in the medical offices of the laboratory (www.kdl.ru), and by ordering a visit of a procedural nurse to your home. Our branches are located not only in Moscow, but also in many regions of the country.

How to get tested for ALT?

For the result of the analysis to be reliable, it is important to follow the recommendations for preparing for the analysis.This analysis is taken on an empty stomach or 3 hours after eating, drinking water is allowed. On the eve of the test, it is necessary to exclude alcohol intake.

ALT blood test results are usually available the next day. Patients of the KDL Clinical Diagnostic Laboratories have access to their personal account on the website www.kdl.ru, where they can always see the history of their visits and the results of all tests being taken. To promptly inform the patient about the readiness of the analysis, SMS notifications are also used.

Explanation of the results of analysis on ALT

Physicians in clinical practice use a special ratio of the concentration of ALT to AST in the blood, called the de Ritis coefficient. In healthy people, it ranges from 0.9 to 1.7. When liver cells are damaged, the ALT level increases more than the AST level, and the de Ritis coefficient decreases. In case of myocardial infarction, on the contrary, the AST level rises faster, which leads to an increase in the coefficient.

Blood test for ALT – biochemistry for alanine aminotransferase to take in Moscow

Alanine aminotransferase (ALT) is an endogenous enzyme related to transaminases.Produced intracellularly. Participates in the metabolism of amino acids. It is found in large quantities in the liver and kidneys, somewhat less in striated muscles.
Plays an important role in the diagnosis of liver pathology. As a rule, it is assigned together with AST.
Alanine aminotransferase (ALT, HPT, GPT, glutamate pyruvate transaminase) is an enzyme that normally has low serum activity in the blood, as it is concentrated inside cells. Its main amount is found in liver cells.ALT begins to be released into the bloodstream if liver damage is present. Moreover, it is often possible to identify this enzyme in the blood much earlier than the first noticeable symptoms appear. Therefore, the Alanine Aminotransferase test is used by specialists as an indicator of liver damage.

Indications for the appointment of a blood test for alanine aminotransferase (ALT):

• Presence of risk factors for liver damage.
• Clinical manifestations characteristic of liver pathologies.
• During treatment, a study is scheduled at regular intervals to monitor the effectiveness of therapy.

General

The liver has many different functions in the body. Its damage leads to the appearance of pain, yellowness of the skin and sclera, nausea, weakness, bloating, fatigue, discoloration of urine and other manifestations. The liver is involved in the synthesis of bile, protein metabolism, the processing of nutrients and other processes in the body.Damage to its cells is manifested by the release of GPT into the blood.
A blood test for ALT (glutamate pyruvate transaminase) is part of a complex of liver tests. It is prescribed by a doctor to check if the patient’s liver is damaged due to medication, previous illness, or other reasons.

A moderate increase in the amount of the enzyme is characteristic of liver tumors. High ALT can be in patients with cirrhosis, biliary obstruction.The abnormalities identified during the study also make it possible to suspect diseases characterized by a slowdown in blood flow to the liver, hepatitis and other viral infections. The amount of the enzyme increases with the use of drugs toxic to the liver, some dietary supplements. The interpretation of the results takes into account the age and gender of the patient. Only a doctor can correctly evaluate the test results. If necessary, he will recommend an examination program or prescribe treatment.
If the test results exceed the norm, this necessarily indicates liver pathology.The indicators increase with intense sports, hard physical work, after injections into muscle tissue. A slight excess of the norm can be observed in people who often eat fast food, as this negatively affects the liver. After switching to a balanced diet, the indicators are normalized without special treatment.

90,000 Liver tests: blood test for liver enzymes in the blood – 30% discount!

Liver test is a comprehensive study that allows you to study the activity of liver enzymes (AST, ALP and ALT).Thanks to this, it is possible to identify diseases of the biliary tract and liver at an early stage. Other vital functions of the body can also suffer from this.

When should liver function tests be done?

Symptoms indicating possible damage to the bile ducts and liver:

• pain in the right hypochondrium;

• persistent nausea;

• lack of appetite;

• the skin becomes unnatural yellow;

• urine darker;

• feces are discolored;

• drowsiness and weakness;

• edema.

When the first symptoms appear, you must immediately consult a doctor. The sooner this is done, the greater the likelihood of successful treatment.

What the results show

Many types of metabolism take place in liver cells. Enzymes of liver cells are involved in this process. An increase in which in the blood is observed during cytolysis of hepatocytes.

If the ALT rate is elevated, this confirms liver damage.

If the AST indicator is increased, then there are fears of a heart attack, muscle damage and hemolysis of erythrocytes.

Acute viral hepatitis is accompanied by an increase in the level of enzymes at least 5 times. In chronic hepatitis, there is an increase of about 2 times. It is strictly not allowed to do self-decryption. The specialist will draw the right conclusions and outline a treatment plan. The earlier therapy is started, the less likely negative consequences are.

Cell damage can be monitored using liver function tests. In some cases, these results are not enough to determine an accurate diagnosis, so additional studies are prescribed.

In addition, liver function tests are suitable for preventive examinations. Doctors recommend doing them to all men and women over 40 at least once a year.

It is also necessary to do such an analysis when taking hepatotoxic drugs in order to monitor the condition of the liver. Only a physician can evaluate the results, confirm the diagnosis and determine the treatment plan.

Liver tests can be performed in our clinic at a favorable price. We employ only experienced specialists who can give qualified advice on any issue.We guarantee promptness and correctness of the results.

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ALT (ALT, Alanine aminotransferase, alanine transaminase, SGPT, Alanine aminotransferase)

Study material
Blood serum

Method of determination
Kinetic UV test (optimized, standardized by DGKC).

Intracellular enzyme involved in the exchange of amino acids.

Catalyzes the transfer of the amino group of alanine to alpha-ketoglutaric acid to form pyruvic acid and glutamic acid. Transamination occurs in the presence of a coenzyme – pyridoxal phosphate – a derivative of vitamin B6.

The highest ALT activity is detected in the liver and kidneys, the lowest in the pancreas, heart, skeletal muscles.The enzyme activity in women is slightly lower than in men. ALT is an intracellular enzyme; its content in the blood serum of healthy people is low. But when cells rich in ALT (liver, heart muscle, skeletal muscles, kidneys) are damaged or destroyed, these enzymes are released into the bloodstream, which leads to an increase in their activity in the blood.

In viral hepatitis, the increase in ALT activity is usually proportional to the severity of the disease. In acute cases, the activity of the enzyme in the blood serum may exceed normal values ​​by 5-10 times or more.