What are ALT and AST liver enzymes. How do doctors interpret ALT and AST test results. What causes elevated liver enzymes. When should you be concerned about abnormal liver function test results.

The Role of ALT and AST in Liver Function

Alanine transaminase (ALT) and aspartate transaminase (AST) are enzymes primarily found in liver cells. These enzymes play crucial roles in amino acid metabolism and energy production within the liver. When liver cells are damaged or die, ALT and AST are released into the bloodstream, causing their levels to rise. This is why measuring ALT and AST levels in blood samples is an essential part of liver function tests.

ALT is considered more specific to liver health than AST, as AST is also present in other tissues such as heart and skeletal muscle. However, both enzymes are typically measured together to provide a more comprehensive picture of liver function.

Functions of ALT and AST

• ALT: Catalyzes the transfer of an amino group from alanine to α-ketoglutarate, forming pyruvate and glutamate
• AST: Catalyzes the reversible transfer of an amino group between aspartate and glutamate

These reactions are essential for the synthesis and breakdown of amino acids, which are the building blocks of proteins. By monitoring ALT and AST levels, healthcare providers can gain valuable insights into the health and functioning of the liver.

Normal Ranges for ALT and AST

The normal ranges for ALT and AST can vary slightly depending on the laboratory and the specific testing method used. However, generally accepted normal ranges for adults are:

• ALT: 7 to 55 units per liter (U/L)
• AST: 8 to 48 U/L

It’s important to note that these ranges may differ for children, older adults, and individuals with certain medical conditions. Additionally, some experts argue that the upper limits of normal should be lower, particularly for ALT.

Are there differences in normal ranges between men and women? Yes, some studies suggest that women tend to have slightly lower ALT and AST levels than men. This is why some laboratories provide gender-specific reference ranges.

Factors Affecting Normal Ranges

Several factors can influence what is considered “normal” for an individual:

1. Age
2. Sex
3. Body mass index (BMI)
4. Ethnicity
5. Alcohol consumption
6. Medication use

Healthcare providers take these factors into account when interpreting liver function test results.

Interpreting Low ALT and AST Levels

While much attention is given to elevated liver enzyme levels, low levels of ALT and AST can also provide important information about a person’s health.

What does it mean if ALT and AST levels are below the normal range? Low levels of these enzymes are generally not a cause for concern and may even be associated with longevity in some studies. However, in certain cases, they may indicate:

• Vitamin B6 deficiency
• Chronic kidney disease
• Frailty in older adults

It’s important to note that low ALT and AST levels alone are rarely used to diagnose any specific condition. Instead, they are considered in conjunction with other clinical findings and test results.

Understanding Elevated ALT and AST Levels

Elevated ALT and AST levels are often the first sign of liver damage or disease. The degree of elevation can provide clues about the underlying cause and severity of liver injury.

Mild Elevations (Less than 5 times the upper limit of normal)

Mild elevations in ALT and AST may be caused by:

• Non-alcoholic fatty liver disease (NAFLD)
• Alcohol-related liver disease
• Chronic hepatitis B or C
• Certain medications
• Obesity

Moderate Elevations (5-15 times the upper limit of normal)

Moderate elevations might indicate:

• Acute viral hepatitis
• Autoimmune hepatitis
• Alcoholic hepatitis
• Drug-induced liver injury

Severe Elevations (More than 15 times the upper limit of normal)

Severe elevations are often seen in:

• Acute liver failure
• Ischemic hepatitis (shock liver)
• Severe drug-induced liver injury

How quickly do ALT and AST levels rise in acute liver injury? In cases of acute liver injury, such as acetaminophen overdose, ALT and AST levels can rise rapidly, often within 24-48 hours of the injury.

The AST/ALT Ratio: A Valuable Diagnostic Tool

The ratio of AST to ALT can provide additional information about the nature of liver damage. This ratio is particularly useful in distinguishing between alcoholic liver disease and other causes of liver injury.

What does an elevated AST/ALT ratio indicate? An AST/ALT ratio greater than 2:1 is suggestive of alcoholic liver disease. In contrast, most other forms of liver injury typically result in an AST/ALT ratio of less than 1:1.

Interpreting the AST/ALT Ratio

• AST/ALT < 1: Typical of viral hepatitis and non-alcoholic fatty liver disease
• AST/ALT > 2: Suggestive of alcoholic liver disease
• AST/ALT > 3: Highly indicative of alcoholic liver disease

It’s important to note that while the AST/ALT ratio can be a helpful diagnostic tool, it should always be interpreted in the context of other clinical findings and test results.

Non-Liver Causes of Elevated ALT and AST

While ALT and AST are primarily associated with liver health, elevated levels can sometimes be caused by conditions affecting other organs or systems in the body.

Muscle-Related Causes

Since AST is also found in muscle tissue, conditions that cause muscle damage can lead to elevated AST levels. These include:

• Strenuous exercise
• Muscle injuries
• Muscular dystrophies
• Rhabdomyolysis

Cardiac Causes

Heart conditions that result in damage to heart muscle can cause elevated AST levels:

• Myocardial infarction (heart attack)
• Congestive heart failure

Other Causes

Additional non-liver causes of elevated ALT and AST include:

• Hemolysis (breakdown of red blood cells)
• Thyroid disorders
• Celiac disease
• Certain medications

How can doctors differentiate between liver and non-liver causes of elevated enzymes? To distinguish between liver and non-liver causes of elevated ALT and AST, doctors typically consider the pattern of elevation, the presence of other abnormal liver tests, and the patient’s clinical presentation. They may also order additional tests, such as creatine kinase (CK) to check for muscle damage.

Monitoring ALT and AST Levels Over Time

Tracking ALT and AST levels over time can provide valuable information about the progression of liver disease, the effectiveness of treatment, and the risk of complications.

Acute vs. Chronic Elevations

The duration of ALT and AST elevation can help differentiate between acute and chronic liver conditions:

• Acute elevations: Typically last less than 6 months and may be caused by viral hepatitis, drug-induced liver injury, or ischemic hepatitis
• Chronic elevations: Persist for more than 6 months and may indicate chronic liver diseases such as chronic viral hepatitis, autoimmune hepatitis, or non-alcoholic fatty liver disease

Treatment Monitoring

ALT and AST levels are often used to monitor the effectiveness of treatments for liver diseases. For example:

• In viral hepatitis treatment, a decline in ALT and AST levels may indicate successful viral suppression
• In autoimmune hepatitis, normalization of enzyme levels suggests good response to immunosuppressive therapy
• In non-alcoholic fatty liver disease, improvements in ALT and AST can reflect the effectiveness of lifestyle modifications

How often should ALT and AST levels be monitored in chronic liver disease? The frequency of monitoring depends on the specific condition and treatment plan. In general, patients with chronic liver diseases may have their ALT and AST levels checked every 3-6 months, or more frequently during active treatment or disease flares.

Prognosis and Risk Assessment

Persistent elevations in ALT and AST can indicate ongoing liver damage and may be associated with an increased risk of liver-related complications. Studies have shown that higher ALT and AST levels are associated with:

• Increased risk of cirrhosis
• Higher likelihood of liver cancer development
• Greater overall mortality in patients with chronic liver disease

Regular monitoring of these enzymes, along with other liver function tests and imaging studies, helps healthcare providers assess the overall health of the liver and make informed decisions about patient care.

When to Seek Medical Attention for Abnormal ALT and AST Levels

While minor fluctuations in ALT and AST levels are common and often don’t require immediate medical attention, there are certain situations where prompt evaluation is necessary.

Signs of Acute Liver Injury

Seek immediate medical attention if you experience any of the following symptoms, especially if you have known liver disease or recent exposure to hepatotoxic substances:

• Jaundice (yellowing of the skin or eyes)
• Severe abdominal pain
• Nausea and vomiting
• Extreme fatigue
• Confusion or altered mental status

These symptoms, particularly when accompanied by very high ALT and AST levels (more than 10-15 times the upper limit of normal), may indicate acute liver failure, which is a medical emergency.

Persistent Mild to Moderate Elevations

If you have mildly elevated ALT and AST levels (less than 5 times the upper limit of normal) that persist for more than 3-6 months, you should consult with your healthcare provider. This could indicate chronic liver disease that requires further evaluation and management.

What steps will a doctor take to investigate persistently elevated liver enzymes? A healthcare provider may:

1. Review your medical history and conduct a physical examination
2. Order additional blood tests to check for specific liver diseases (e.g., hepatitis B and C, autoimmune markers)
3. Recommend imaging studies such as ultrasound or CT scan of the liver
4. Consider a liver biopsy in some cases

Monitoring Known Liver Conditions

If you have a known liver condition, your healthcare provider will give you specific guidelines on when to seek medical attention based on your ALT and AST levels. In general, you should contact your provider if:

• Your enzyme levels increase significantly from your baseline
• You develop new symptoms of liver disease
• You experience side effects from liver-related medications

Regular follow-up and open communication with your healthcare provider are essential for managing liver health and preventing complications.

Understanding ALT and AST levels is crucial for monitoring liver health and detecting potential liver diseases early. While these enzymes provide valuable information, they are just one piece of the puzzle in assessing overall liver function. Always consult with a healthcare professional for proper interpretation of liver function test results and personalized medical advice.

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.

Products & Services

Show more products from Mayo Clinic

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.

More Information

Show more related information

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.

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

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.

Why Would I Need This Test?

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

Other reasons to have this test:

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.

How Do I Prepare?

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.

What Happens During the 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.

What Are the Risks?

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

What Do the Results Mean?

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

Continued

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:

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:

Will I Take Other Tests?

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:

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.

AST/ALT Ratio – an overview

How to interpret liver function tests

Author(s): Christina Levick

Translational Gastroenterology Unit, University of Oxford, UK

Correspondence: Christina Levick [email protected]

Abstract

Careful interpretation of liver function tests within the clinical context can help elucidate the cause and severity of the underlying pathology. Predominantly raised alkaline phosphatase represents the cholestatic pattern of biliary pathology, whilst predominantly raised alanine aminotransferase and aspartate aminotransferase represent the hepatocellular pattern of hepatocellular pathology. The severity of liver dysfunction or biliary obstruction is reflected in the bilirubin level and the degree of liver synthetic function can also be indicated by the albumin level. Beyond the liver function tests, prothrombin time provides another marker of liver synthetic function and a low platelet count suggests portal hypertension.

Key words: Liver function test, cholestatic pattern, hepatocellular pattern, liver synthetic function.

Introduction

Derangement of liver function tests (LFTs) is a common problem that can be difficult to interpret. The clinical context is an important guide, but liver disease can be asymptomatic until the late stages and abnormal blood tests may be the first indication of disease. This review will guide you through the individual LFT’s and how to interpret them.

What are the LFTs?

LFTs include liver enzymes, albumin and other proteins, and bilirubin. The liver enzymes are produced by cells within the liver. They include alkaline phosphatase (ALP), ɣ–glutamyl transpedtidase (GGT), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), but the combination of liver enzyme results you receive depends on your local laboratory. The protein components comprise total protein, albumin and globulin [N.B. Total protein = Albumin + Globulins]. The globulins are a mixture of globular proteins such as immunoglobulins, enzymes, carrier proteins and complement.

The LFT’s reflect a limited range of hepatic metabolic processes. Bilirubin is an indication of the detoxification/excretory function and albumin reflects the synthetic function.

Typical normal ranges for LFTs and other blood tests are shown in Table 1, but may vary according to your local laboratory.

Table 1. Normal values for blood tests

Liver enzymes

The liver enzymes are in two main groups – ALP and GGT, produced predominantly by the bile ducts; and ALT and AST, produced predominantly by hepatocytes. Liver enzymes are a poor reflector of liver function, but rather of cholestasis and liver cell integrity, respectively [1].

Liver enzymes have different normal ranges, so assessment of their relative abnormalities by number of times greater than their upper limit of normal (ULN) can be more informative than the absolute values.

When ALP is raised more times its ULN than either ALT or AST, this suggests a cholestatic pattern indicating biliary pathology. In the acute setting, a cholestatic pattern of LFTs is seen with bile stones, when accompanied by colicky right upper quadrant pain or in cholestatic drug-induced liver injury when there is a history of a new causative medication. A more chronic presentation may be due to pancreatic, liver or bile duct tumours or cholestatic autoimmune liver disease such as primary biliary cholangitis or primary sclerosing cholangitis.

ALP is also produced outside the liver by organs such as bone, placenta, kidneys and gut.  Hence ALP may be raised in the presence of normal liver health, most commonly due to bone disease or pregnancy. A raised GGT and/or other abnormalities in the LFTs would indicate a liver source of raised ALP. The ALP isoenzyme can also help differentiate a liver versus bone origin. If all other liver tests are normal, raised calcium or phosphorus levels may also indicate a bone source.

GGT is induced by alcohol and other drugs and so lacks specificity for many liver diseases, except in the context of ALP.

ALT and AST are produced mostly by hepatocytes. However, ALT occurs at low concentrations in skeletal muscle and kidney, and AST is found in kidney, heart, brain, red blood cells and skeletal muscle [1]. Abnormalities in ALT and AST are fairly specific to the liver however.

When ALT or AST are raised more times their ULN than ALP, this is described as a hepatocellular pattern. This state reflects disease processes affecting hepatocytes such as viral hepatitis, metabolic liver diseases, drug or alcohol toxicity and autoimmune hepatitis. Abnormalities in these liver enzymes are generally considered mild if <5 times the ULN, moderate if 5-10 times the ULN or marked if >10 times the ULN.

In alcoholic hepatitis, an ALT over 300 IU/l is rare, but increased AST/ALT ratio is often observed. In contrast, the AST/ALT ratio is low in non-alcoholic steatohepatitis [2], often accompanied by a modestly elevated GGT. Although there are many differential diagnoses for mild to modest elevations in ALT or AST, marked elevations are usually only caused by acute drug-induced liver injury, viral hepatitis or ischaemic liver injury. Detailed history for drug and toxin exposure, viral hepatitis risk factors and inter-current illness resulting in hypotension should be taken. The patient should also be monitored for fulminant liver failure.

In reality, the pattern of LFTs may not be clear-cut and an apparently hepatocellular pattern can reflect an acute cholestatic cause such as biliary stones. Typically, the raised ALT or AST in this situation resolves quickly once the obstruction is relieved. Clinical context and further assessments are therefore needed to help make the diagnosis. The timing of liver enzyme abnormalities may differentiate acute from chronic liver disease, but note that in the chronic setting, significant liver damage such as cirrhosis can exist with normal liver enzyme levels. Raised liver enzymes are not a reliable screening test for cirrhosis.

Bilirubin

Bilirubin is the product of haemoglobin breakdown. Lipid-soluble, unconjugated bilirubin is conjugated in the liver, making it water-soluble, and then excreted into bile. When a raised bilirubin or clinical jaundice is found we should consider haemolysis (production of unconjugated bilirubin), liver cell function (conjugation and excretion of bilirubin) and biliary tree function (excretion of bile). A raised bilirubin level is a strong indicator of underlying pathology and should always be investigated with a careful clinical history and appropriate investigations. A liver ultrasound is usually necessary.

In haemolysis, red cell rupture releases free haemoglobin, raising blood levels of unconjugated bilirubin. The diagnosis of haemolysis may be supported by reduced haemoglobin, reduced haptoglobins, increased reticulocyte count and an abnormal blood film, whilst other LFTs and liver ultrasound are normal.

Unconjugated bilirubin is also raised in Gilbert’s syndrome, a benign, inherited disease. Patients are well in Gilbert’s syndrome, but their bilirubin levels may rise particularly during inter-current illnesses, whilst other liver tests and liver ultrasound remain normal. Gilbert’s syndrome can be diagnosed clinically.

In liver cell or biliary pathology with a raised bilirubin, a hepatocellular or cholestatic liver enzyme pattern is often present and possible abnormalities in liver synthetic function. Consideration of these other LFTs, the clinical history and a liver ultrasound to look for biliary obstruction, liver lesions or liver parenchymal change are useful.

Unlike the liver enzymes, the bilirubin can be a useful marker of liver function, as bilirubin rises with increasing severity of liver disease. Bilirubin has been incorporated into a number of composite scores, which assess liver disease severity including the Child Pugh [3] and model for end-stage liver disease (MELD) scores [4][3].

Albumin

Albumin is a protein synthesized exclusively in the liver. As such it is a marker of liver synthetic function and liver health. The half-life of albumin is 20 days and so a low albumin may be seen in chronic or sub-acute liver disease, but may not be observed in acute liver injury [1]. Albumin levels can be reduced by many kinds of illnesses and so has relatively low specificity as a marker of liver function. None-the-less a low albumin has prognostic significance and forms part of the Child Pugh score.

Other assessments of liver function

The LFTs are not the only blood tests indicating liver function. In particular the prothrombin time (PT) or international normalised ratio (INR), and platelet count contribute to a more comprehensive assessment.

The PT is governed by the activity of clotting factors, which are produced by the liver and have a half-life of about one day [1]. The production of these clotting factors is dependent on adequate vitamin K and so clotting may also be prolonged by vitamin K deficiency. In the absence of vitamin K deficiency or anticoagulants (e.g. warfarin), PT is a good marker of liver function in both acute and chronic settings. The international normalized ratio (INR) also reflects clotting and liver synthetic function in the same way and unlike PT, is standardised across laboratories. Liver function must be quite severely impaired to affect PT or INR and so mild liver disease or a state of compensated cirrhosis will likely have normal values. The PT and INR form part of the Child Pugh and MELD scores, respectively.

Importantly, the liver makes both clotting and fibrinolytic products and so it should not be assumed that a raised PT indicates a hypocoagulable state in the context of liver disease.

Cirrhosis can cause increased pressure in the portal vein that carries blood from the gut and the spleen to the liver. This is called portal hypertension. When this develops, the spleen becomes engorged with blood and consumes platelets. A low platelet count is a marker of portal hypertension [5] and may be the first indicator of chronic liver disease. Portal hypertension causes many of the complications of chronic liver disease such as variceal bleeds, ascites and hepatic encephalopathy and so the finding of a low platelet count in this context is a poor prognostic sign.

The underlying etiology

Despite meticulous interpretation of the LFTs, the underlying cause of liver disease may still not be apparent. When presented with a patient with liver test abnormalities or a clinical suspicion of chronic liver disease, it is often necessary to perform a liver screen. Detailed discussion of the liver screen is beyond the context of this article, but is summarised in Table 2. The liver screen does not contain specific tests for alcohol-related liver disease, non-alcoholic fatty liver disease (NAFLD) or drug-induced liver injury amongst others, so careful history and assessment of liver disease risk factors are still vital.

In the acute setting, hepatitis A, hepatitis E, Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus and stool examination for schistosomiasis ova may also be considered.

Table 2. Chronic liver disease screen

Simple non-invasive scores of liver fibrosis

Although the simple presence of raised liver enzyme levels is not a reliable way of diagnosing cirrhosis, liver function blood tests can be used in combination to predict the presence of liver fibrosis. Detailed description and discussion of these scores is beyond the scope of this article, but commonly used scores include the AST/ALT ratio [6], AST to platelet ratio index (APRI) [7], fibrosis 4 (FIB-4) [8] and NAFLD fibrosis risk score [9]. The World Health Organisation recommends the use of APRI or FIB-4 scores for the assessment of chronic hepatitis C related liver fibrosis to aid decision-making on hepatitis C treatment allocation [10].

Summary

Deranged LFTs are a common problem and their interpretation is complicated by the production of liver enzymes from multiple organs and the lack of specificity for markers of liver function.  Therefore it is important to interpret liver tests within the clinical context. Raised ALP reflects biliary tree injury and cholestasis, whereas raised AST and ALT levels usually reflect hepatocyte injury. Raised bilirubin and low albumin are the LFT components that can reflect impaired liver function, whilst raised PT or INR also provide a marker of liver synthetic function. A low platelet count may be seen in cirrhosis and signify the onset of portal hypertension.

References

1.  Giannini EG, Testa R, Savarino V. Liver enzyme alteration: a guide for clinicians, CMAJ 2005; 172(3):367-79.
2. Sorbi D, Boynton J, Lindor KD, The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating nonalcoholic steatohepatitis from alcoholic liver disease, Am J Gastroenterol 1999; 94(4):1018-22.
3.  Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices, Br J Surg 1973; 60(8):646-9.
4.  Kamath PS, Wiesner RH, Malinchoc M, Kremers W, etal. A model to predict survival in patients with end-stage liver disease, Hepatology 2001; 33(2): 464-70.
5.  de Franchis R, Baveno VIF Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension, J Hepatol 2015; 63(3):743-52.
6. Williams AL, Hoofnagle JH. Ratio of serum aspartate to alanine aminotransferase in chronic hepatitis. Relationship to cirrhosis, Gastroenterology 1988; 95(3):734-9.
7.  Wai CT, Greenson JK, R.J. Fontana RJ. etal. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C, Hepatology 2003; 38(2):518-26.
8.  Vallet-Pichard A, Mallet V, Nalpas B etal. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest, Hepatology 2007; 46(1):32-6.
9. Angulo P, Hui JM, Marchesini G, etal. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD, Hepatology 2007; 45(4):846-54.
10.  World Health Organization.  Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection, Guidelines for the Screening, Care and Treatment of Persons with Hepatitis C Infection, Geneva, 2014.

Liver Enzyme Interpretation and Liver Function Tests

Reviewing the interpretation and limitations of serum liver enzyme activity and liver function tests for dogs and cats.

Brigitte B. McAteeDVM

Brigitte B. McAtee received her DVM from Auburn University. She is currently a second-year internal medicine resident at Texas A&M University in College Station, Texas. Her clinical and research interests include infectious and immune-mediated diseases.

Jonathan A. LidburyBVMS, MRCVS, PhD, DACVIM, DECVIM-CA

Jonathan A. Lidbury graduated from the University of Glasgow and completed his internal medicine residency at Texas A&M University. Jonathan is an assistant professor of small animal internal medicine and the associate director for clinical services of the Gastrointestinal Laboratory at Texas A&M University. His clinical interests are small animal hepatology and gastroenterology, and he is involved in a wide range of research in these fields.

Hepatobiliary disease is an important cause of morbidity and mortality in dogs and cats and can present a diagnostic challenge for two main reasons. First, patient signalment varies because liver disease and dysfunction can occur in cats and dogs of any age, sex, or breed (see Case Studies). Despite this, the patient’s signalment can sometimes give important clues because certain breeds have disease predispositions; for example, Labrador retrievers are predisposed to copper-associated chronic hepatitis. Second, elevations of serum liver enzyme activities are commonly encountered in small animal practice but are not specific for primary liver disease. However, early in the course of liver diseases, such as chronic hepatitis, patients may have no or only subtle, nonspecific clinical signs, such as intermittent anorexia or lethargy. In these patients, increased liver enzyme activities may be the first indicator of a problem. More liver-specific clinical signs, such as icterus, ascites, edema, polyuria/polydipsia, and hepatic encephalopathy, tend to occur late in the course of disease, when it is often too late to prevent its progression. Therefore, early diagnosis of liver disease often relies on serum biochemical testing, which may prompt further diagnostics, including liver function testing. This article reviews the interpretation and limitations of serum liver enzyme activity and liver function tests.

CASE STUDIES

Case 1

Signalment and Presentation

A 3-month-old female intact Irish wolfhound presents for stunted growth and episodes of intermittent lethargy and disorientation.

Results of Diagnostic Testing

A serum biochemistry panel is performed, with the results in Table A. The fasted ammonia concentration is 175 mcg/dL (normal range, 0–50 mcg/dL). Preprandial and postprandial (2-hour) SBA are 40 mcmol/L (normal, 0–8 mcmol/L) and 102 mcmol/L (normal, 0–30 mcmol/L), respectively.

Interpretation

The combination of hypoalbuminemia, decreased BUN, and hypocholesterolemia suggests decreased hepatic synthetic capacity. The ALT and AST activities are within normal limits, making hepatocellular damage unlikely; the ALP activity is only mildly elevated, probably because the dog is growing.

The ammonia concentration and SBA results suggest portosystemic shunting and/or hepatic insufficiency.

Given the patient’s signalment, clinical findings, and laboratory abnormalities, a congenital portosystemic shunt is likely and imaging (ultrasonography and/or computed tomography) is warranted.

Case 2

Signalment and Presentation

An 8-year-old male neutered Labrador retriever presents for a 3-month history of decreased appetite and weight loss.

Results of Diagnostic Testing

A serum biochemistry panel is performed, with the results in Table B. The fasted ammonia concentration is <15 mcg/dL (normal range, 0–50 mcg/dL). Preprandial and postprandial (2-hour) bile acids are 2.9 mcmol/L (normal, 0–8 mcmol/L) and 14.5 mcmol/L (normal, 0–30 mcmol/L), respectively.

Interpretation

The ALT activity is 2.4 times the upper limit of the reference interval, while the ALP activity is only 1.3 times the upper limit of the reference interval. This, along with the increased serum AST activity, is consistent with a hepatocellular damage pattern.

The ammonia concentration and SBA results rule out portosystemic shunting and do not support the presence of severe liver dysfunction. However, hepatobiliary disease is not excluded and further testing is indicated.

Abdominal ultrasonography would be a logical next step. If the ALT is persistently increased and no evidence supports the presence of extrahepatic disease, liver biopsy would be indicated.

BACKGROUND

The liver has a wide variety of metabolic functions (Box 1). Because of these diverse metabolic roles, liver dysfunction is associated with a variety of sequelae and clinicopathologic abnormalities.

The liver is unique in that it receives much of its blood supply (75%) from the portal venous system, which drains abdominal organs, such as the gastrointestinal (GI) tract, spleen, and pancreas.^1,2 This means that diseases of the pancreas and GI tract can secondarily affect the liver. The liver also metabolizes and/or excretes a variety of exogenous substances (ie, drugs and toxins) that may cause secondary liver injury.

HEPATIC ENZYMOLOGY

Serum liver enzymes are sensitive but not necessarily specific markers of primary hepatobiliary disease. They are not direct markers of liver function. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular damage, whereas alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) are markers of cholestasis.³ Each individual enzyme can provide information on whether liver disease is present and may provide clues as to the most likely differential diagnosis.

Alanine Aminotransferase

ALT is a cytoplasmic enzyme found mainly in hepatocytes. However, it is also found in other cells, such as skeletal muscle, renal, and red blood cells, in smaller amounts. ALT is released into the circulation when there is hepatocyte necrosis or increased cell membrane permeability and therefore is a sensitive marker of hepatocellular injury. ALT is the most liver specific of the liver enzymes, but occasionally severe muscle damage or ex vivo hemolysis may increase ALT activity.⁴ Concurrent evaluation of creatine kinase activity may help discriminate between muscle disease and liver disease because creatine kinase activity is expected to increase with muscle damage. ALT activity can also be increased in patients with extrahepatic diseases that secondarily affect the liver (eg, feline hyperthyroidism). The reported half-life of ALT has been reported to be about 60 hours in dogs and 3.5 hours in cats.³ These relatively short half-lives are useful when monitoring recovery after acute liver injury. Conditions that can cause an increase in ALT activity include those listed in Table 1.

Aspartate Aminotransferase

AST is a cytoplasmic and mitochondrial enzyme found in hepatocytes and other cells. Reversible or irreversible damage to the liver causes release of the cytoplasmic AST; however, only irreversible damage to the cell will cause release of mitochondrial AST. These two sources of AST are not distinguishable by measuring serum AST activity on a routine biochemistry panel.

Increases in AST activity generally parallel those of ALT. However, AST is less specific for liver injury than ALT because increases in activity of AST may also be due to cardiac or skeletal muscle injury⁴ or ex vivo hemolysis. The half-life of AST is about 22 hours in dogs and 80 minutes in cats.³ The shorter half-life compared with ALT means that AST activity decreases and returns to normal before that of ALT in patients with acute liver injury. Conditions that can cause an increase in AST activity include those listed in Table 1.

Alkaline Phosphatase

ALP is an enzyme found in hepatocytes that line the bile canaliculi. It is released into the circulation during intra- or extrahepatic cholestasis. This enzyme is sensitive for hepatobiliary disease in dogs (80%), but because of the possible contributions of bone and glucocorticoid-induced isoenzymes to serum ALP activity, its specificity is low (51%).⁵ In young, growing animals, ALP activity is normally increased because of the bone isoenzyme, with 71% of dogs younger than 1 year having ALP activity >150 U/L.⁶ Bone ALP may also be elevated in patients with osteomyelitis or osteosarcoma. Dogs with hyperadrenocorticism and those receiving glucocorticoids can be expected to have increased ALP activity due to the glucocorticoid-induced isoenzyme. Conditions that can cause an increase in ALP activity include those listed in Table 1.

The highest activities of ALP have been reported with conditions such as cholestasis, steroid hepatopathy, chronic hepatitis, and hepatic necrosis.⁷ This lack of tissue specificity can make increases in activity of ALP hard to interpret. The half-life of ALP is approximately 70 hours in dogs and 6 hours in cats.³ In cats, which lack the glucocorticoid-induced isoenzyme with a shorter half-life, increases of serum ALP activity are more specific for hepatobiliary disease than in dogs and are generally clinically relevant.

Gamma-Glutamyltransferase

GGT is associated with the cell membranes of hepatocytes that form the bile canaliculi and bile ducts, as well as periportal hepatocytes. It is a marker of intrahepatic (eg, feline hepatic lipidosis) or extrahepatic (eg, bile duct obstruction) cholestasis. In dogs, it has a higher specificity (87%) and lower sensitivity (50%) for hepatobiliary disease compared with ALP.⁷ In general, GGT is a more sensitive marker of feline hepatobiliary disease than ALP. However, in cats with feline hepatic lipidosis, GGT is generally only mildly elevated.⁸ No definitive studies determining the half-life of GGT have been performed in cats or dogs. However, serum GGT and ALP activities decrease after liver injury at a similar rate in dogs, suggesting that they have a similar half-life.⁹

Interpreting Liver Enzyme Elevations

The degree of the increase in hepatocellular-damage enzyme activities may help stratify disease severity as follows⁵:

• Mild: 2- to 3-fold elevation in activity
• Moderate: 5- to 10-fold elevation in activity
• Marked: >10-fold elevation

However, such increases do not always correlate with severity of disease. This is true in dogs and cats with portosystemic shunting and dogs with end-stage chronic hepatitis, in which hepatocytes are replaced by fibrous tissue. Therefore, the degree of liver enzyme increase should be interpreted with caution.

Because the liver has a large regenerative capacity, the degree of liver enzyme elevation should also not be used to indicate prognosis. For example, a dog with acute liver injury may have severely increased serum ALT activity but can still make a full recovery. Longitudinal monitoring trends in liver enzyme activities can help in determining chronicity and monitoring disease progression and/or response to treatment.

In evaluating liver enzymes, it is important to determine what type of elevation pattern is present (ie, hepatocellular damage versus cholestasis). A relatively greater increase in ALT and AST activity indicates hepatocellular damage, while a greater increase in ALP and GGT activity indicates cholestasis, which could be intrahepatic or extrahepatic. Establishing the pattern may help narrow the differential diagnosis. However, some liver diseases can display a mixed pattern (eg, cholangitis, phenobarbital hepatopathy).

LIVER FUNCTION TESTING

Routine biochemical testing can give clinicians an insight into many liver functions. Box 2 presents common abnormal results of biochemical tests that can have liver-related causes as well as important differential diagnoses to consider for these test results. However, because of the liver’s functional reserve capacity, these tests are not sensitive for liver insufficiency. Abnormal results can also be caused by other conditions and thus also lack specificity.

It is important for clinicians to not only look for analytes that are flagged as being outside their respective reference intervals but also look at their actual values. For example, serum albumin, cholesterol, and blood urea nitrogen (BUN) concentrations toward the lower limit of the reference interval suggest hepatic insufficiency or portosystemic shunting. Monitoring trends in these values over time can also be informative.

Because of the limited sensitivity and specificity of biochemical tests, patients with confirmed or suspected liver disease sometimes require additional liver function testing to better characterize their disease.

Serum Bile Acids

Measurement of the total concentrations of serum bile acids (SBA) aids in the diagnosis of patients with portosystemic shunts and in the assessment of hepatic function. Potential indications for SBA measurement include:

• Suspicion for portosystemic shunting (eg, seizures, other signs of encephalopathy)
• Persistently increased liver enzyme activities, especially ALT
• Severe hypoalbuminemia (<2.0 g/dL) in dogs
• Unexplained ammonium urate urolithiasis
• Hyperbilirubinemia when hemolysis cannot be definitely diagnosed/excluded (uncommon)

In a healthy patient, SBA are synthesized from cholesterol. In dogs, bile acids are conjugated to glycine or taurine and then stored in the gallbladder, whereas in cats they are conjugated almost exclusively with taurine.¹⁰ After a meal, the gallbladder contracts because of secretion of cholecystokinin, emptying bile into the duodenum. Bile acids are absorbed in the ileum. They are transported via the portal circulation to the liver, where they are subsequently reabsorbed. Normally this process is about 95% to 98% efficient.

The enterohepatic recirculation of bile acids is impeded in dogs without gallbladders and patients with ileal disease or that have had ileal resection, causing a decrease in SBA concentration. Other conditions that can cause decreased SBA concentrations include GI malabsorption and decreased gastric motility.² Causes of increased total SBA concentrations are listed in Box 2. Diseases that cause intrahepatic cholestasis (lipidosis, diabetes mellitus, lymphoma, histoplasmosis, cirrhosis) or extrahepatic cholestasis (cholangitis, bile duct carcinoma, liver flukes, cholelithiasis, pancreatitis) can cause decreased bile acid excretion, despite no decrease in functional hepatic mass. In patients with hyperbilirubinemia, once hemolysis has been ruled out, measuring SBA is not indicated because their concentration will be predictably increased.

Compared with plasma ammonia, SBA are easy to measure and do not not require special sample handling. Paired preprandial and 2-hour postprandial SBA measurements are usually performed to increase the sensitivity of this test (Box 3). While SBA measurement is arguably the best test of liver function and portosystemic shunting in dogs and cats, increased concentrations are not specific for any single hepatobiliary disease. Therefore, this test can be helpful for evaluating the likelihood of hepatobiliary disease; however, it cannot definitively determine the underlying liver disease. Additionally, this test does not provide a truly quantitative assessment of hepatic function. Because of the hepatic reserve capacity, it is possible for dogs with normal SBA concentrations to have hepatobiliary disease; therefore, this test should not be used to screen patients for hepatobiliary disease. However, the sensitivity of SBA measurement for portosystemic shunts (congenital and acquired) is high and in one study was reported to be 93% and 100% for dogs and cats with congenital portosystemic shunt, respectively.¹¹

Ammonia

Blood ammonia concentration can be increased because of portosystemic shunting, severe hepatic insufficiency, or urea cycle enzyme deficiencies (Box 4).¹² Potential indications for plasma ammonia measurement include:

• Suspicion for portosystemic shunting
  (eg, seizures, other signs of encephalopathy)
• Suspicion for urea cycle enzyme deficiency
  (eg, cat with feline hepatic lipidosis)
• Unexplained ammonium urate urolithiasis

Ammonia is mainly produced by catabolism of glutamine by enterocytes and bacterial degradation of urea and proteins in the large bowel. Therefore, blood coming from the splanchnic circulation is rich in ammonia. ¹³ The liver detoxifies ammonia through two pathways: (1) the urea cycle, which converts ammonia into urea and (2) consumption of ammonia during glutamine synthesis by hepatocytes. In animals with portosystemic shunting or severe hepatic dysfunction, the liver is unable to synthesize sufficient glutamine or urea, leading to hyperammonemia. Because ammonia freely passes across membranes, including the blood–brain barrier, hyperammonemia contributes to the development of clinical signs of hepatic encephalopathy.

Fasting Ammonia Measurement

Ammonia testing requires heparinized tubes, transfer of the sample on ice, and urgent separation of plasma and is ideally performed within 30 minutes of sample collection. These requirements can make this diagnostic assay difficult to perform in private practice. Increased serum ammonia is a sensitive marker for congenital and acquired portosystemic shunts, with a reported sensitivity of 83% to 98%.^11,14 However, in the absence of portosystemic shunting, ammonia is not a sensitive test of liver disease.

Ammonia Tolerance Test

When ammonia is administered orally or rectally to a normal dog, it should be efficiently extracted from the portal circulation by the liver. However, dogs with a portosystemic shunt or decreased hepatic functional mass cannot extract the additional ammonia, leading to an excessive increase in plasma ammonia concentration.

The main indication for this test is concern for hepatic insufficiency that is not supported by routine laboratory testing. This test is unnecessary for dogs with increased baseline ammonia, in addition to posing a risk for hepatic encephalopathy in these patients. Disadvantages of oral ammonia administration include¹⁵:

• Absorption depends on gastric emptying.
• Vomiting can occur.
• It is stressful to the patient.
• The taste of the ammonium chloride is unpleasant.

The rectal ammonia tolerance test avoids these problems (Box 5). ¹⁶ However, we do not routinely perform either test in dogs or cats.

Postprandial Venous Ammonia Tolerance Test

The postprandial ammonia tolerance test involves a procedure similar to that of the oral or rectal ammonia tolerance test except that digested food provides the ammonia challenge and the disadvantages of oral administration are avoided. The patient is fed a commercial diet containing about 30% protein to provide 33 kcal/kg, and a blood sample is collected 6 hours after feeding. This test was reported to have 91% sensitivity for the detection of portosystemic shunting, but in the absence of portosystemic shunts it is not as sensitive for detecting hepatic insufficiency.¹⁷

Protein C

Protein C is an anticoagulant protein produced by the liver. Measurement of protein C provides information regarding liver function and perfusion. In one study,¹⁸ dogs with congenital and acquired portosystemic shunts, hepatic failure, and chronic hepatitis had decreased levels of protein C, which distinguished them from dogs with microvascular dysplasia (portal vein hypoplasia) and those without hepatobiliary disease. With use of a cutoff value of 70% activity, protein C could distinguish dogs with congenital portosystemic shunt from those with microvascular dysplasia with a sensitivity of 93% and a specificity of 88%.

CONCLUSIONS

Increased liver enzyme activities are common results in small animal practice and can suggest patterns of liver disease, including hepatocellular damage, cholestasis, or both. Liver enzymes, especially ALP, are not specific for primary liver disease. To evaluate their clinical significance, a combination of history, clinical signs, physical examination, diagnostic imaging, and other liver function test results must be considered. Changes such as hypocholesterolemia or hypoalbuminemia can suggest hepatic dysfunction. Measuring SBA or ammonia concentrations provides a more accurate assessment of liver function, but it is important to be aware that patients with normal liver function test results can still have liver disease. Although these laboratory tests play an important role in diagnosing canine and feline liver disease, definitive diagnosis usually requires a combination of diagnostic imaging and cytologic or histologic assessment of liver tissue.

References

1. Hall JE, Guyton AC. Guyton and Hall Textbook of Medical Physiology, 12th ed. Philadelphia: Saunders/Elsevier; 2011.
2. Allison RW. Laboratory evaluation of the liver. In: Thrall M, Weiser, G, Allison RW, Campbell TW (eds): Veterinary Hematology and Clinical Chemistry, 2nd ed. Oxford: John Wiley & Sons; 2012:401-424.
3. Lidbury JA, Steiner JM. Diagnostic evaluation of the liver. In: Washabau RJ, Day MJ, eds: Canine & Feline Gastroenterology. St. Louis, MO: Elsevier Saunders; 2013:863-875.
4. Valentine BA, Blue JT, Shelley SM, et al. Increased serum alanine aminotransferase activity associated with muscle necrosis in the dog. J Vet Intern Med 1990; 4(3):140-143.
5. Webster CRL, Cooper JC. Diagnostic approach to hepatobiliary disease. In: Bonagura J, Twedt D, eds. Kirk’s Current Veterinary Therapy, 15th ed. St. Louis, MO: Elsevier; 2014:569-575.
6. Comazzi S, Pieralisi C, Bertazzolo W. Haematological and biochemical abnormalities in canine blood: frequency and associations in 1022 samples. J Small Anim Pract 2004; 45(7):343-349.
7. Center SA, Slater MR, Manwarren T, et al. Diagnostic efficacy of serum alkaline phosphatase and gamma-glutamyltransferase in dogs with histologically confirmed hepatobiliary disease: 270 cases (1980-1990). JAVMA 1992; 201(8):1258-1264.
8. Center SA, Baldwin BH, Dillingham S, et al. Diagnostic value of serum gamma-glutamyl transferase and alkaline phosphatase activities in hepatobiliary disease in the cat. JAVMA 1986; 188(5):507-510.
9. Kaneko JJ, Harvey J, Bruss ML. Diagnostic enzymology of domestic animals. In: Clinical Biochemistry of Domestic Animals, 6th ed. St. Louis, MO: Elsevier; 2008:358-361.
10. Rabin B, Nicolosi RJ, Hayes KC. Dietary influence on bile acid conjugation in the cat. J Nutr 1976; 106(6):1241-1246.
11. Ruland K, Fischer A, Hartmann K. Sensitivity and specificity of fasting ammonia and serum bile acids in the diagnosis of portosystemic shunts in dogs and cats. Vet Clin Pathol 2010; 39(1):57-64.
12. Center SA, ManWarren T, Slater MR, et al. Evaluation of twelve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs. JAVMA 1991; 199(2):217-226.
13. Lidbury JA, Cook AK, Steiner JM. Hepatic encephalopathy in dogs and cats. J Vet Emerg Crit Care (San Antonio) 2016; 26(4):471-487.
14. Gerritzen-Bruning MJ, van den Ingh TS, Rothuizen J. Diagnostic value of fasting plasma ammonia and bile acid concentrations in the identification of portosystemic shunting in dogs. J Vet Intern Med 2006; 20(1):13-19.
15. Meyer DJ, Strombeck DR, Stone EA, et al. Ammonia tolerance test in clinically normal dogs and in dogs with portosystemic shunts. JAVMA 1978; 173(4):377-379.
16. Rothuizen J, van den Ingh TS. Rectal ammonia tolerance test in the evaluation of portal circulation in dogs with liver disease. Res Vet Sci 1982; 33(1):22-25.
17. Walker MC, Hill RC, Guilford WG, et al. Postprandial venous ammonia concentrations in the diagnosis of hepatobiliary disease in dogs. J Vet Intern Med 2001; 15(5):463-466.
18. Toulza O, Center SA, Brooks MB, et al. Evaluation of plasma protein C activity for detection of hepatobiliary disease and portosystemic shunting in dogs. JAVMA 2006; 229(11):1761-1771.

The AST and ALT levels on your blood test results – what do they mean?

AST and ALT are two common markers for diagnosing liver diseases. Patients with liver disorders often find their AST and ALT levels unsatisfactory, but what do the figures actually imply? And do patients of every kind of liver dysfunctions have the same levels?

AST:ALT ratio

Although the normal range of AST and ALT level varies among laboratories and countries, the ratio of AST:ALT is key when it comes to diagnosing liver diseases. The use of this ratio was first suggested by de Ritis in 1955. He found that the ratio decreased in patients with acute viral hepatitis and increased in patients with cirrhosis.

The AST:ALT ratio in a healthy individual would be around 1.15. If the ratio is more than 2.0 (up to 6.0), this denotes alcoholic liver disease. And if the ratio is between 1.4 and 2.0, it suggests cirrhosis. Interestingly enough, the severity of cirrhosis is measured by the level of the ratio, implying that patients of cirrhosis with a high AST:ALT ratio would probably have a more advanced case of cirrhosis. On the other hand, patients with acute viral hepatitis often have a very low AST:ALT ratio, ranging from 0.5 to 0.8.

Since AST level will increase significantly after one consumes alcohol, it could also be a marker for alcohol consumption. However, it should be noted that most patients with high alcohol consumption but without severe liver disease often do not have an AST/ALT ratio above 1, which means that a high ratio could probably be a result of advanced alcoholic liver disease.

Here’s an easy way to find out your AST:ALT ratio: divide your AST level as shown on your blood test results by your ALT level. For example, if your AST is 20 U/L and your ALT is 18 U/L, then your ALT ratio would be 1.05, which is within the normal range.

What is the magnitude of AST and ALT elevations for acute viral hepatitis?

Not only is the AST:ALT ratio useful when it comes to diagnosing liver diseases, the magnitude of AST and ALT elevations is also a crucial marker when it comes to differentiating the type of liver diseases patients have. One of the most obvious diseases that can be diagnosed through this method is acute viral hepatitis. In a research study of 15 laboratory tests, it was shown that all acute viral hepatitis patients showed an AST level greater than 200 U/L and an ALT level greater than 300 U/L, which both are 25 times the upper limit of normal levels.

Are AST and ALT elevations always related to liver diseases?

Since AST is found in various organs like liver, kidneys, heart, skeletal muscles, and brain, elevation of AST level could also be related to acute cardiac or skeletal muscle injury. A lesser degree of ALT elevation could also signal skeletal muscle injury or it is simply a bodily reaction after vigorous exercise. Therefore, AST and ALT elevations do not always suggest hepatic conditions, even though care should still be given when such situations occur.

Treatments

Despite the wide range of causes for AST and ALT elevations, it should never be ignored or viewed as a temporary issue. Since the increased levels of AST and ALT suggest the liver is inflamed, patients could try ways to lower the levels by first stopping any form of alcohol intake, followed by doing regular exercises and maintaining a balanced diet with sufficient portions of whole grains, leafy green vegetables, and dairy products. If necessary, patients could always try taking liver supplements that are safe and proven to help lower both the AST and ALT levels. Once both levels are controlled, it is a good indication that the liver is no longer inflamed or damaged.

AST/ALT

AST/ALT

Alanine aminotransferase
(ALT) and Aspartate aminotransferase (AST)

Alanine aminotranferease (ALT) and aspartate
aminotransferase (AST) are enzymes located in liver cells that
leak out into the general circulation when liver cells are
injured. These two enzymes were previously known as the SGPT
(serum glutamic-pyruvic transaminase) and the SGOT (serum
glutaic-oxaloacetic transaminase). These two transaminase enzymes
may be reported on lab slips with both their new names and
previous names or by their newer names only. ALT and AST are
present in highest concentrations in cells from the liver, heart,
skeletal muscles, and red blood cells. Patients whose LFTs show a
predominant rise in the transaminases have liver diseases that
are characterized by hepatocellular damage.

ALT is found predominately in the liver, with
lesser quantities found in the kidneys, heart, and skeletal
muscle. As a result, the ALT is a more specific indicator of
liver inflammation than the AST, as the AST may also be elevated
in diseases affecting other organs, such as the heart or muscles.
The AST is also elevated after a myocardial infarction, and
during acute pancreatitis, acute hemolytic anemia, severe burns,
acute renal disease, musculoskeletal diseases, and trauma.
Because intramuscular (IM) injections cause muscle trauma that
may release AST and ALT into the bloodstream, IM injections
should be avoided before LFTs are done. If an IM injection must
be given close to the time blood for LFTs is drawn, the nurse
should indicate on the lab slip the time the injection is given.
Many liver enzyme tests are also affected by medications. It is
important to consult the laboratory manual for medications that
should be considered in the interpretation of test results, and
to indicate such medications on the lab slip.

Instant Feedback:

ALT is a
more specific indicator of liver inflammation than the AST.

TRUE or FALSE

In acute liver injury, such as viral hepatitis,
the ALT and AST may be as high as 1000U/L. In chronic hepatitis
or cirrhosis of the liver, ALT and AST may be 10 to 100 times
their normal values.

Total protein in whey

This is a measurement of the concentration of total protein (albumin + globulins) in the liquid part of the blood, the results of which characterize the exchange of proteins in the body.

Russian synonyms

Total protein, total serum protein.

Synonyms English

Total Protein, Serum Total Protein, Total Serum Protein, TProt, TR.

Research method

Colorimetric photometric method.

Units

G / L (grams per liter).

What biomaterial can be used for research?

Venous, capillary blood.

How to properly prepare for the study?

• Do not eat for 12 hours before testing.
• Eliminate physical and emotional stress 30 minutes before the study.
• Do not smoke within 30 minutes prior to examination.

General information about the study

The total protein content in blood serum reflects the state of protein metabolism.

Proteins predominate in the composition of the dense residue of blood serum (liquid part that does not contain cellular elements). They serve as the basic building blocks for all cells and tissues of the body. Enzymes, many hormones, antibodies and blood clotting factors are built from proteins. In addition, they perform the function of carriers of hormones, vitamins, minerals, fat-like substances and other metabolic components in the blood, and also provide their transport into cells.The osmotic pressure of the blood depends on the amount of proteins in the serum, due to which a balance is maintained between the water content in the tissues of the body and within the vascular bed. It determines the ability of water to be retained in the circulating blood and maintain tissue elasticity. Proteins are also responsible for maintaining the correct acid-base balance (pH). Finally, it is a source of energy for malnutrition or starvation.

Serum proteins are divided into two classes: albumin and globulins.Albumin is synthesized in the liver from food. Their amount in plasma affects the level of osmotic pressure, which retains fluid within the blood vessels. Globulins perform an immune function (antibodies), provide normal blood clotting (fibrinogen), and are also represented by enzymes, hormones and carrier proteins of various biochemical compounds.

Deviation of the level of total blood protein from the norm can be caused by a number of physiological conditions (not pathological in nature) or be a symptom of various diseases.It is customary to distinguish between relative deviation (associated with a change in the water content in the circulating blood) and absolute (caused by changes in metabolism – the rate of synthesis / decay – of whey proteins).

• Physiological absolute hypoproteinemia can occur with prolonged bed rest, in women during pregnancy (especially in its last third) and breastfeeding, in children at an early age, that is, in conditions of insufficient intake of protein from food or an increased need for it …In these cases, the total protein in the blood decreases.
• Development physiological relative hypoproteinemia (lowering the level of total protein in the blood) is associated with excess fluid intake (increased water load).
• Relative hyperproteinemia (increased total protein in the blood) can be caused by excess water loss such as excessive sweating.
• Relative pathological (associated with any disease) hyperproteinemia is caused by significant loss of fluid and thickening of the blood (with profuse vomiting, diarrhea or chronic nephritis).
• Pathological relative hypoproteinemia is observed in the opposite cases – with excessive fluid retention in the circulating blood (impaired renal function, deterioration of the heart, some hormonal disorders, etc.).
• An absolute increase in total blood protein can occur in acute and chronic infectious diseases due to increased production of immune globulins, in some rare health disorders characterized by intensive synthesis of abnormal proteins (paraproteins), in liver diseases, etc.

The absolute hypoproteinemia has the greatest clinical significance. An absolute decrease in the concentration of total protein in the blood most often occurs due to a decrease in the amount of albumin. A normal level of albumin in the blood is an indicator of good health and proper metabolism, and vice versa, a low level indicates a low vitality of the body. At the same time, the loss / destruction / insufficient synthesis of albumin is a sign and indicator of the severity of some diseases.Thus, the analysis for total blood protein makes it possible to detect a significant decrease in the viability of the organism in connection with any reasons important for health or to take the first step in diagnosing a disease associated with a violation of protein metabolism.

Depletion of albumin reserves in the blood can occur with malnutrition, diseases of the gastrointestinal tract and difficulties in assimilating food, chronic intoxication.

Diseases associated with a decrease in the amount of blood albumin include some disorders in the liver (a decrease in protein synthesis in it), kidneys (loss of albumin in the urine as a result of a violation of the blood filtration mechanism in the kidneys), certain endocrine disorders (disorders of hormonal regulation of protein metabolism ).

What is the research used for?

• As part of the first stage of a comprehensive examination in the process of diagnosing various health disorders.
• To identify and assess the severity of nutritional disorders (with intoxication, malnutrition, diseases of the gastrointestinal tract).
• In order to diagnose various diseases associated with disorders of protein metabolism, and to assess the effectiveness of their treatment.
• For monitoring physiological functions during long-term clinical observations.
• To assess the functional reserves of the body in connection with the prognosis for the current disease or forthcoming medical procedures (drug therapy, surgery).

When is the study scheduled?

• For the initial diagnosis of a disease.
• With symptoms of exhaustion.
• If you suspect a disease associated with any disorders of protein metabolism.
• When assessing the state of metabolism or the thyroid gland.
• When examining liver or kidney function.
• With long-term clinical observation of the course of treatment of diseases associated with disorders of protein metabolism.
• When considering the possibility of a surgical operation.
• During a preventive examination.

What do the results mean?

Reference values ​​(norm of total protein in blood)

The results of the analysis for total protein in the blood serum allow to assess the state of health, rationality of nutrition and the function of internal organs by their effectiveness in maintaining normal protein metabolism.If a deviation from the norm is detected, further examination is required to clarify its cause.

Reasons for an increase in the level of total protein in the blood

• Acute and chronic infection (including tuberculosis),
• dysfunction of the adrenal cortex,
• autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, scleroderma),
• allergic conditions,
• some rare systemic diseases,
• fluid loss (diabetic acidosis, chronic diarrhea, etc.)),
• respiratory failure,
• destruction of red blood cells,
• active chronic hepatitis,
• some rare blood diseases.

Reasons for a decrease in the level of total protein in the blood

• Fluid retention due to impaired renal function or weakened heart function,
• insufficient intake of protein in the body or impaired absorption of food in the gastrointestinal tract (due to starvation, malnutrition, narrowing of the esophagus, inflammatory bowel disease),
• decrease in protein synthesis in the liver (due to hepatitis, cirrhosis / liver atrophy, intoxication),
• congenital disorders of the synthesis of individual blood proteins,
• increased protein breakdown (as a result of malignant neoplasms, hyperfunction of the thyroid gland, postoperative condition, prolonged fever, trauma, long-term treatment with hormonal anti-inflammatory drugs),
• excessive protein loss in kidney disease, diabetes mellitus, bleeding,
• loss of protein together with fluid that accumulates in the abdominal cavity and pleural cavity.

What can influence the result?

Food intake can significantly increase blood protein levels, while after exercise it decreases. The protein concentration can also be influenced by the use of tea, coffee, alcohol, and medicines. In addition, for the most accurate result, the patient should refrain from food with a significant amount of fat.

Download an example of the result

Also recommended

Who orders the study?

General practitioner, therapist, endocrinologist, rheumatologist, cardiologist, hematologist, oncologist, pulmonologist, obstetrician-gynecologist, infectious disease specialist, allergist, pediatrician, gastroenterologist, surgeon.

Literature

• Blood Biochemistry. N J Russell, G M Powell, J G Jones, P J, Winterburn and J M Basford, Croom Helm, London and Canberra, 1982
• Blood Chemistry and CBC analysis-Clinical Laboratory Testing from a Functional Perspective. Rychard Weatherby N.D and Scott Fergusson, N.D., Bear Mounting Publishing, 2002
• Tietz Clinical Guide to Laboratory Tests. Alan H. B. Wu, Saunders / Elsevier, 2006
• Laboratory and Diagnostic Tests.Joyce LeFever Kee – Pearson, Prentice Hall, 8th Edition 2010
• District Laboratory Practice in Tropical Countries. Monica Cheesbrough, Cambridge University Press, second edition, 2005
• Clinical Chemistry. A Laboratory Perspective. Wendy L. Arneson, Jean M. Brickell, F. A. Davis Company, 2007
• Clinical Chemistry. Michael L. Bishop, Edward P. Fody, Larry E. Schoef, Lippincott Williams & Wilkins 2005

How to Interpret ALT, AST, Bilirubin, Alkaline Phosphatase Tests

The American College of Gastroenterology (ACG) has issued updated guidelines for biochemical blood tests used to assess liver health

New guidance is targeted at both professionals and primary care providers.

Specific values ​​for the normal range of alanine aminotransferase (ALT) levels are provided, as well as stepwise screening algorithms for elevated ALT, aspartic aminotransferase (AST), alkaline phosphatase and bilirubin. In comparison with the documents of the previous editions, the new recommendations contain reduced limits of the norm. Those. In the previous recommendations, the upper limits of indicators (ULN) were considered as the norm, which can vary significantly between laboratories with in the range of 30-40 international units (IU) per liter in some institutions and up to 70-80 IU / L in others.According to the new guidelines, the normal range for ALT would be 19-25 IU / L for women and 29-33 IU / L for men.

Cirrhosis of the liver. Questions and Answers

The authors noted that they are aware that due to the lowering of the normal limits, many patients will fall into the category with increased indicators and that this will create certain difficulties for doctors.

However, the authors consider lower starting points to be justified, pointing out that sometimes even the smallest elevation in ALT significantly increases the risk of death due to liver disease.

The authors point out that elevated ALT levels help identify people with chronic liver disease, such as non-alcoholic fatty liver disease, as well as chronic hepatitis C and B.

over time, its level does not return to normal. The authors hope that over time, practitioners will become accustomed to these new levels, leading to improved liver health for all, as well as overall health.

Key Recommendations

1. Before evaluating liver function abnormalities, repeat the laboratory panel and / or perform an explanatory test (for example, a GGT test if serum alkaline phosphatase is elevated) to confirm that the blood livers are not actually normal. (Strong recommendation, very low level of evidence).
2. Testing for chronic hepatitis C is done with anti-HCV and confirmation is done with HCV-RNA by nucleic acid testing.Risk factors for hepatitis C include a history of intranasal or intravenous drug use, tattoos, body piercings, blood transfusions, and high-risk sexual behavior. Also at risk are people born between 1945 and 1965. Testing for acute hepatitis C is done with anti-HCV and HCV RNA by nucleic acid testing. (Strong recommendation, very low level of evidence).
3. Testing for chronic hepatitis B is done with HBsAg testing.Acute hepatitis B testing is associated with HBsAg and anti-HBc IgM.
   The following groups are at greatest risk: people born in endemic or hyperendemic areas (HBsAg prevalence> 2%), men who have sex with men, people who have ever injected drugs, dialysis patients, HIV-infected individuals, pregnant women and family members, family members and sexual contacts of HBV-infected individuals. (Strong recommendation, very low level of evidence).
4. Testing for acute hepatitis A (IgM HAV) should be performed in patients with acute hepatitis and suspected fecal-oral exposure. Acute hepatitis E (IgM HEV) testing should also be done in those returning from endemic areas who are negative for acute hepatitis A, B, and C. (Strong recommendation, very low level of evidence).
5. Patients with an elevated BMI and other features of metabolic syndrome, including diabetes mellitus, overweight or obesity, hyperlipidemia, or hypertension with mildly elevated ALT levels should undergo an ultrasound screening for non-alcoholic fatty liver disease (NAFLD).(Strong recommendation, very low level of evidence).
6. Women who consume more than 140 grams of alcohol per week or men who consume more than 210 grams per week who have AST> ALT should be considered at risk for alcoholic liver disease and should be advised to stop drinking. (Strong recommendation, very low level of evidence).
7. All patients with abnormal liver function tests in the absence of acute hepatitis should be tested for hereditary hemochromatosis with iron, transferrin, and serum ferritin levels.HFE gene mutation analysis should be performed in patients with a transferrin score ≥45% and / or elevated serum ferritin. (Strong recommendation, very low level of evidence).
8. Patients with abnormal AST and ALT levels, especially those with other autoimmune conditions, should be tested for autoimmune liver disease including ANA, ASMA, and globulin levels. (Strong recommendation, very low level of evidence).
9. Patients with persistently elevated AST and ALT levels, especially those under the age of 55, should be screened for Wilson’s disease with serum ceruloplasmin testing.When ceruloplasmin is found to be low, confirmatory testing with 24-hour urine copper and slit-lamp examination of the eyes for abnormalities (Kaiser-Fleischer mosaic rings) is recommended. (Strong recommendation, very low level of evidence).
10. Patients with persistently elevated AST or ALT should be screened for alpha-1 antitrypsin deficiency (A1AT) with an alpha-1 antitrypsin phenotype (Strong recommendation, very low level of evidence).
11. Physicians should ask patients with abnormal kidney tests about the drugs and medicines they are taking, including those that they take on their own, without a doctor’s recommendation. It is also worth considering dietary or herbal supplements that may be associated with DILI. (Strong recommendation, very low level of evidence).
12. A liver biopsy may be considered when serologic testing and imaging are unable to identify a diagnosis, interpret a condition, or when multiple diagnoses are possible.(Strong recommendation, very low level of evidence).
13. An increase in alkaline phosphatase should be confirmed by an increase in GGT. Given the lack of specificity for liver disease, GGT should not be used as a screening test for underlying liver disease in the absence of other abnormal liver findings. (Strong recommendation, very low level of evidence).
14. Patients with elevated alkaline phosphatase with or without elevated bilirubin should be tested for PBC (formerly called primary biliary cirrhosis) with antimitochondrial antibody testing.(Strong recommendation, very low level of evidence).
15. Patients with elevated alkaline phosphatase with or without elevated bilirubin should be tested for PSC by MR cholangiography or ERCP with IgG4. (Strong recommendation, very low level of evidence).
16. In patients with ALT and / or AST levels <5X ULN, laboratory testing should evaluate the possibility of viral hepatitis B and C, alcoholic and NAFLD, hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, autoimmune hepatitis and consider the possibility of drug poisoning and associated liver damage.(Strong recommendation, very low level of evidence).
17. In individuals with ALT and / or AST 5-15X ULN, acute hepatitis A, B, and C should be considered in addition to all eiologies (Strong recommendation, very low level of evidence).
18. In individuals with ALT and / or AST> 15X ULN or a massive increase in ALT> 10,000 IU / L, acetaminophen toxicity and ischemic hepatopathy (shock liver) should be considered. (Strong recommendation, very low level of evidence).
19. A patient with acute hepatitis with increased prothrombin time and / or encephalopathy requires immediate referral to a specialist hepaologist. specialist in the liver. (Strong recommendation, very low level of evidence).

ALT, alanine aminotransferase; ANA, anti-nuclear antibodies; ASMA, anti-smooth antibody; AST, aspartate aminotransferase; BMI, body mass index; DILI, drug-induced liver damage; GGT, gamma glutamyl transferase; HAV, hepatitis A virus; HBc, the main antigen of hepatitis B; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; HEV, hepatitis E virus; HFE, hereditary hemochromatosis; IgM, immunoglobulin M; MR, magnetic resonance; NAFLD, non-alcoholic fatty liver disease; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; ULN, upper limit of norm

The following contributors took part in the preparation of the recommendations:

Division of Gastroenterology / Hepatology, Department of Medicine, Stanford University School of Medicine Palo Alto, California, USA; Digestive Health Institute, University Hospitals Cleveland Medical Center and Division of Gastroenterology and Liver Disease, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA; Yale Viral Hepatitis Program, Yale University School of Medicine.New Haven, Connecticut, USA. Correspondence: Paul Y. Kwo, MD, FACG, Division of Gastroenterology / Hepatology, Stanford University School of Medicine, 750 Welch Road, Suite 210, Palo Alto, California 94304, USA

Retrieved from http://acgblog.org/

The norm of ALT and AST in women in the blood by age, indicators

ALT and AST are one of the indicators of the state of health that are taken into account in the biochemical study of the venous blood of the expectant mother. What to do if their level exceeds the permissible level and what processes reflect these indicators?

What are ALT and AST?

The abbreviation ALT stands for alanine aminotransferase, and AST stands for aspartate aminotransferase.These are protein-containing enzymes that are part of almost all cells in the body, forming their basis and affecting protein synthesis.

These enzymes can be detected in the blood after the destruction of the cells in which they were contained. High concentrations of ALT and AST are found in various organs. Cell destruction is a normal process, and trace amounts of enzymes are present in the blood of a perfectly healthy person. However, a significant increase in the concentration of these substances indicates one of the following processes:

• acute hepatitis;
• cardiac ischemia;
• liver cirrhosis;
• blockage of the bile ducts;

90,043 pregnancies.

Determine the serum enzyme level by biochemical analysis. Tracking the level of these enzymes becomes especially important during pregnancy, therefore, when their concentration increases, the woman is sent for additional examinations.

How do you know about an enzyme boost?

A biochemical blood test allows you to identify the amount of liver enzymes.

Checking the content of ALT and AST in pregnant women is included in the complex of standard diagnostic procedures.The indicators are assessed several times during pregnancy. In addition, when an increased content of liver enzymes is detected, additional tests are carried out, reflecting the state of carbohydrate, fat metabolism and some other important characteristics.

The norm of ALT and AST in women has no clear boundaries. The content of substances may fluctuate slightly, especially in pregnant women. In addition, the amount of enzymes can change after stress or change with age. During pregnancy, an increase in the level of liver enzymes in the blood is due to the fact that the liver of the mother’s body experiences a double load.

are considered the norm in women the following values ​​of ALT and AST:

• for AST – not more than 31 U / L in the first trimester and not more than 30 U / L starting from II;
• for ALT – no more than 32 U / L at the beginning of pregnancy, after – no more than 31 U / L.

It should be noted that the specific values ​​of these indicators may differ from one laboratory to another. The normal range should be indicated on the test result sheet. Differences may be due to the sensitivity of the equipment used for analysis in a particular institution.

What if enzyme levels are elevated?

With a single detection of abnormal liver enzymes, the woman is carefully examined. A one-time excess of quantitative norms may be a consequence of the natural development of the fetus, but it may also indicate a developing disease, which must be treated to preserve the health of the child and the expectant mother.

When an increase in the level of liver enzymes is detected again, the doctor collects anamnestic data and prescribes additional studies.Indicators may increase due to the action of the following pathological processes:

• medicinal hepatitis;
• autoimmune hepatitis;
• viral liver diseases;
• cholecystitis;
• liver cirrhosis;
• fatty atrophy of the liver;
• late forms of toxicosis.

Additional studies in this case are liver ultrasound and specific blood tests.

Probable reasons for an increase in ALT and AST

As mentioned above, during pregnancy, the body of the expectant mother experiences significant overload, and therefore any provoking factor can lead to disruption of the organ. Therefore, doctors are cautious in prescribing drugs, knowing the risk of drug-induced hepatitis. However, sometimes you have to choose between a potential risk to the liver and a real threat to a woman’s life.

Antibiotics, hormonal agents, antiepileptic drugs, and non-steroidal anti-inflammatory drugs are especially dangerous.It is also appropriate to recall the dangers of alcohol: it not only negatively affects the development of the fetus, but also harms the expectant mother.

Autoimmune hepatitis is a rare congenital disorder that may first appear during pregnancy. This diagnosis can be identified by analysis for specific markers of the disease.

Viral liver diseases mean various variants of hepatitis, therefore clinics carry out a mandatory test for this disease before planning pregnancy.Do not forget also about the danger of infection directly during pregnancy: even a harmless trip to the manicure room can lead to infection with hepatitis, if the sterilization of instruments is not given due attention there.

Cholecystitis is an inflammation of the walls of the gallbladder. In the event of an acute attack of cholecystitis, the patient is admitted to the surgical department, where the optimal treatment is carried out taking into account the pregnancy.

Whatever the reason for the increase in liver enzymes, you should undergo a thorough examination to identify it.Treatment usually involves several specialists to develop an optimal therapy strategy.

Read more: INR rate in blood in women

Clinical Study Healthy: GD Antrodia camphorata – Clinical Trials Registry

Press Center – Mindray

Gong Xiaolin
Center for Clinical Laboratory

With critical damage to the liver, heart and other organs of the human body, large amounts of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatine kinase and other enzymes are released, which significantly increases their concentration in the peripheral blood.Under such conditions, the concentration of these enzymes significantly exceeds the linearity ranges of the reagents. There is a high degree of probability of very rapid consumption of substrates in the reagent, as a result of which the reaction will cease to be a zero-order reaction, and the results of the analysis will be significantly lower than the actual concentration.

Mindray BS Series Biochemistry Analyzers with built-in Substrate Depletion Limits provide a warning in the event of substrate depletion. When a substrate depletion is detected during a reaction, the instrument initiates a linearity extension function and, using the photometric points with a reaction time ramp, by default, (or delay time), calculates the ∆A / min ratio and gives the appropriate results.

Automatic biochemistry analyzer BS-2000M2 is a modular device for performing biochemical analyzes. This is a proprietary development of Mindray Medical Bioelectronics Co, Ltd. In this study, a number of standard biochemical tests (ALT, AST, ALP, GGT, LDH, α-HBDH, CK, CK-MB, α-AMY and UREA) were performed on samples with a high concentration of analytes to give an overall assessment of the expansion function linearity range of reagents for determining the concentration of enzymes in the BS_2000M2 device in clinical practice.

Materials and methods

Sample source

The research team collected blood serum samples from the outpatient and inpatient departments of Xuhui Hospital of Fudan Zhongshan University. A total of 63 samples were collected with a high concentration of analyzed components (ALT, AST, ALP, GGT, LDH, α-HBDH, CK, CK-MB, α-AMY and UREA). The concentration values ​​of these substances were divided into three groups: below the upper limit of the linearity range, close to the upper limit of the linearity range, and above the upper limit of the linearity range.All samples showed no visible signs of hemolysis and lipidemia.

Instruments and reagents

BS-2000M2 instrument, original reagent kits, calibrators and QC materials designed to perform analyzes for ALT, AST, ALP, GGT, LDH, α-HBDH, CK, CK-MB, α-AMY and UREA concentration were acquired from Mindray Medical Bioelectronics Co., Ltd., Shenzhen.

Methodology

First, calibrate and maintain the instrument according to the manufacturer’s instructions and recommendations.Verify that the calibrations and quality control procedures for all reagents used were successful.

The basic principle of the function of expanding the linearity range of reagents for determining the concentration of enzymes is that after completion of the reaction, the system searches for absorption points with a linear change during the reaction period in accordance with the limit value of substrate depletion. If the number of absorption points ramping during the reaction period (N) is 1 or 0, the system initiates the linearity range expansion function and searches for linear absorption points without depleting the substrate during the delay period, and then calculates △ A / min for these points and reports the resulting result (Fig.one). If the obtained result exceeds the upper limit of the reagent linearity range, the system sets the “>” flag. If the number of absorption points with linearity range change in the delay period (N) is still 1 or 0, the result cannot be calculated. The system sets the ENC flag to indicate this error. The system then automatically dilutes and retests the sample to obtain a normal result.

Figure 1. Principle of the function of expanding the linearity range of reagents for determining the concentration of enzymes

Discussion

The clinical performance of a biochemistry analyzer is influenced by many factors: specific instrument characteristics, reagent characteristics, analysis protocol, traceability of manufacturer’s parameters, daily calibration and laboratory maintenance, etc.e. When choosing a biochemical analyzer, laboratory staff should pay special attention to the possibility of automatic monitoring of substrate depletion in kinetic tests.

In this study, the BS-2000M2’s linearity range extension function proved to be effective. The results showed that the upper limits of the range of the ten tests included in the report were expanded to 3339 U / L, 7411 U / L, 3407 U / L, 3945 U / L, 7646 U / L, 9783 U / L, 14106 U / L, 3296 U / L, 9700 U / L and 54 mmol / L, respectively (Tab.one). It can be concluded that in each test, when the result was below the previously indicated maximum, the relative deviation between the result using the linearity extension function of the enzyme reagents and the repeated result after dilution remained clinically acceptable. In addition, there was no false warning or failure to detect substrate depletion during the study.

Table 1. Recorded range of 10 biochemical tests with kinetic reaction method

Figure 2. Software built-in ALT Substrate Depletion Label Index and Optional Linearity Expansion Function for Enzyme Concentration Reagents

Conclusion

It can be concluded that the function of expanding the linearity range of reagents for determining the concentration of enzymes of the BS-2000M2 significantly increases the recorded range, which effectively reduces the risk of false negative results in samples with a high concentration of components, reduces the frequency of retesting and the processing time of samples.

Gratitude

Special thanks to Mr. Song Yunxiao, Laboratory of Xuhui Hospital of Fudan Zhongshan University for his assistance in collecting samples for this study.

This article originally appeared in Laboratory Medicine Issue 32/9 September 2017.

Original title: Substrate Depletion Limit Parameters: Role of substrate depletion limit parameters in BS-2000M2 automatic chemistry analysis system)

This article is only a fragment of the original text.See original text for relevant data and full content.

normal range – Russian translation

Elevated transaminases

In medicine, the presence of elevated transaminases , usually alanine transaminase (ALT) and aspartate transaminase (AST) transaminases, may be an indicator of liver damage.Other terms used include transaminasemia , transaminite (which some sources consider pathologically meaningless) and elevated liver enzymes (although they are not the only enzymes in the liver). Normal ranges for both ALT and AST are 8-40 U / L with mild transaminesia noted up to the upper numerical limit of 250 U / L. Drug-induced increases such as those found with anti-TB agents such as isoniazid are usually limited to levels below 100 U / L for ALT or AST.Liver cirrhosis or fulminant liver failure associated with hepatitis usually reaches values ​​for both ALT and AST in the range> 1000 U / L. Elevated transaminases that persist for less than six months are called “acute” in nature, and those that persist for six months or more are called “chronic” in nature.

Pathophysiology

There are transaminases in the liver, which synthesize and break down amino acids, and also convert accumulator molecules.Serum (non-cellular blood) concentrations of these transaminases are usually low. However, if the liver is damaged, the membrane of liver cells (hepatocytes) becomes more permeable and some enzymes enter the bloodstream.

Two transaminases are commonly measured: alanine transaminase (ALT) and aspartate transaminase (AST). These levels were previously referred to as serum glutamate pyruvate transaminase (SGPT) and serum glutamate oxaloacetate transaminase (SGOT) . The elevated levels are susceptible to liver damage, which means that they may be present when there is damage.However, they can also be elevated in other conditions such as thyroid disease, celiac disease, and muscle disorders.

ALT is usually found only in the liver. AST is most commonly found in the liver, but also in significant amounts in the heart (cardiac) and skeletal muscles.

ALT and AST measurements have been used to diagnose heart attacks, although they have been superseded by newer tests for enzymes and proteins that are more specific for heart damage.

Possible causes of high ALT levels: liver inflammation (hepatitis A, B, C, infectious mononucleosis, acute viral fever, alcohol, pancreatic disease), muscle damage (trauma, myocardial infarction, congestive heart failure, acute renal failure) and many others … toxins and drugs.

Role in diagnosis

In general, any liver injury causes a moderate rise in these transaminases, but diagnosis requires the synthesis of many pieces of information, including the patient’s history, physical examination, and possibly imaging or other laboratory tests.