What is considered high ast and alt levels. The Surprising Link Between COVID-19 and Abnormal Liver Tests

03.09.202326.06.2023 by alexxlab

What is the link between COVID-19 and high liver enzyme levels? Are abnormal liver tests associated with poorer outcomes in COVID-19 patients? Discover the surprising findings from the Yale Liver Center study.

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COVID-19 and Abnormal Liver Test Rates

Researchers at the Yale Liver Center found that patients with COVID-19 presented with abnormal liver tests at much higher rates than previously suggested by earlier studies. The study, which looked at 1,827 COVID-19 patients hospitalized in the Yale New Haven Health system, discovered that the incidence of abnormal liver tests ranged from 41.6% to 83.4% of patients, depending on the specific test. This is significantly higher than the 15% rate of abnormal liver tests reported in previous studies from China.

Liver Enzyme Elevations and COVID-19 Outcomes

The Yale study also found that higher levels of liver enzymes, such as aspartate aminotransferase (AST) and alanine transaminase (ALT), were associated with poorer outcomes for COVID-19 patients. These included increased rates of ICU admission, mechanical ventilation, and death. The researchers note that the liver is likely a “bystander” affected by the hyperinflammation and side effects of treatments associated with severe COVID-19 cases, rather than the liver itself driving the poorer outcomes.

Potential Reasons for Higher Abnormal Liver Test Rates

The researchers do not fully understand why the incidence of abnormal liver tests was so much higher in the Yale study compared to previous studies in China. They speculate that the difference may be due to other underlying health factors in the U.S. population, such as higher rates of alcoholic or non-alcoholic fatty liver disease, as well as chronic hepatitis B or C. In the U.S., close to one-third of people have fatty liver disease, and several million have chronic viral hepatitis.

Pre-existing Liver Conditions and COVID-19

The researchers found that approximately one-quarter of patients in the study had abnormal liver tests prior to being admitted for COVID-19. Regardless of whether patients had existing liver problems or developed them during their COVID-19 hospitalization, a strong association was observed between abnormal liver tests and the severity of the COVID-19 cases.

COVID-19 Treatments and Liver Damage

The study also noted a relationship between certain drugs used to treat severe COVID-19 and liver damage, most significantly the drug tocilizumab. However, the researchers were unable to confidently determine whether the abnormal liver tests were due to “drug-induced liver injury” or were a result of the COVID-19 disease itself.

Advancing COVID-19 and Liver Research

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

Recognizing Abnormal Liver Test Patterns

While a single abnormal liver function test provides limited diagnostic information, recognizing a pattern of abnormalities can help determine the origin of the issue. Liver test abnormalities can be divided into three main patterns: hepatocellular (indicating liver cell inflammation), cholestatic (indicating bile duct obstruction), and isolated hyperbilirubinemia (indicating liver dysfunction).

Does COVID-19 typically cause abnormal liver tests? Yes, the Yale Liver Center study found that the incidence of abnormal liver tests in COVID-19 patients was much higher than previously reported, ranging from 41.6% to 83.4% of patients.

Are abnormal liver tests associated with worse COVID-19 outcomes? Yes, the study found a strong association between higher levels of liver enzymes, such as AST and ALT, and poorer outcomes for COVID-19 patients, including increased rates of ICU admission, mechanical ventilation, and death.

Why might the incidence of abnormal liver tests be higher in the U.S. compared to China? The researchers speculate that the difference may be due to other underlying health factors in the U.S. population, such as higher rates of fatty liver disease and chronic viral hepatitis, which are more common in the U.S. than in China.

Can pre-existing liver conditions impact COVID-19 outcomes? Yes, the study found that approximately one-quarter of patients had abnormal liver tests prior to being admitted for COVID-19, and these pre-existing liver problems were associated with more severe COVID-19 cases.

Can COVID-19 treatments contribute to liver damage? Yes, the study noted a relationship between the use of certain COVID-19 medications, particularly tocilizumab, and abnormal liver tests, though the researchers could not confidently determine if the liver damage was due to the drugs or the COVID-19 disease itself.

How is the Yale Liver Center contributing to COVID-19 and liver research? As one of only four National Institutes of Health-sponsored liver centers in the country, the Yale Liver Center is uniquely positioned to advance research on COVID-19’s impact on liver pathology, and they have additional clinical and lab-based studies underway to further understand this relationship.

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

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

The study appeared online on July 29 in Hepatology.

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

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

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

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

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

Dr. Michael Nathanson

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

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

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

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

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

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

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

Recognizing a hepatocellular pattern on a liver function panel

Learn how to recognize a hepatocellular pattern of an abnormal liver function panel. Click here to read more!

Amer Wahed, MD FRCPath

3m read

Editors:Shelley Jacobs, PhD

Peer reviewers:Franz Wiesbauer, MD MPH Internist

Last update26th Jan 2021

An abnormality in a single liver function test provides us with limited diagnostic information. But, if we can recognize a pattern of abnormality in our findings, it can help us to determine the origin of the abnormality. Liver test abnormalities can be divided into three patterns:

Hepatocellular (indicating hepatocellular disease)
Cholestatic (indicating intrahepatic or extrahepatic biliary obstruction)
Isolated hyperbilirubinemia (indicating conjugated or unconjugated hyperbilirubinemia)

Each of these may be acute (e.g., present for less than 6 weeks), subacute (e.g., present for 6 weeks–6 months), or chronic (e.g., present for more than 6 months).

Figure 1. The three abnormal patterns that can be detected in liver function tests include the hepatocellular pattern, cholestatic pattern, and isolated hyperbilirubinemia pattern, each of which can be acute, subacute, or chronic in presentation.

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How do you recognize a hepatocellular pattern?

Let’s discuss the hepatocellular pattern of liver test abnormalities. With the hepatocellular pattern, serum aminotransferases, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are significantly elevated. Alkaline phosphatase (ALP) levels are mildly elevated (typically less than three times the normal level), and serum bilirubin levels are also elevated.

Tests for synthetic function, such as prothrombin time (PT) and albumin levels, may also be abnormal. If they are abnormal, PT and albumin levels are typically decreased.

Table 1. Liver function testing abnormalities that are common with hepatocellular diseases.

Common causes of hepatocellular diseases include viral hepatitis, drug-induced liver damage, and chronic liver disease. The most common chronic liver disease is cirrhosis resulting from alcohol abuse or autoimmune hepatitis.

Figure 2. A hepatocellular pattern on a liver testing panel could indicate viral hepatitis, drug-induced liver damage, or chronic liver disease.

What do relative levels of AST and ALT tell us in a clinical setting?

Let’s outline a few key points that may be clinically useful when it comes to identifying a hepatocellular pattern on a liver function panel.

If ALT and AST values are 8 times greater than the upper limit of the normal range, a hepatocellular pattern of disease is more likely. If ALT and AST values are 25 times greater than normal, the diagnosis is likely viral hepatitis or drug-induced liver damage. However, if ALT and AST are 50 times greater than normal, it suggests ischemic hepatic damage from insufficient blood flow secondary to shock or low blood pressure. With nonalcoholic steatohepatitis, ALT and AST are less than 4 times the upper limit of normal. Lastly, an AST to ALT ratio that is greater than 2:1 suggests alcoholic liver disease.

Table 2. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) testing results and their implications.

What should you do if you recognize this pattern in your patients?

In individuals with hepatocellular patterns of liver function test abnormalities (e.g., significant elevation of ALT and AST), there are seven tests you should consider running to help diagnose the cause:

Acetaminophen levels
Viral hepatitis serology
Toxicology screen
Autoimmune markers (if indicated)
Antinuclear antibodies
Anti-smooth muscle antibodies
Anti-liver kidney microsomal type 1 antibodies

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About the author

Amer Wahed, MD FRCPath

Amer is a Professor and Vice Chair (Clinical Pathology) and Associate Residency Program Director in the Department of Pathology and Laboratory Medicine at the University of Texas, Health Science Center at Houston, USA.

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Recognizing a cholestatic pattern on a liver function panel

Learn how to recognize a cholestatic pattern of an abnormal liver function panel. Click here to read more!

By Amer Wahed, MD FRCPath • Last update 26th Jan 2021 • 3m read

Aspartate aminotransferase (AST) / AST | CSD Medical Laboratory

Aspartate aminotransferase (AST) is an enzyme found in all cells of the body, but mainly in the heart and liver, and to a lesser extent in the kidneys and muscles. In healthy patients, the activity of aspartate aminotransferase in the blood is low and the norm of aspartate aminotransferase has low values. When the liver or muscles are damaged, aspartate aminotransferase is released, the level of aspartate aminotransferase in the blood increases. In this regard, the activity of this enzyme is an indicator of liver damage. Analysis of aspartate aminotransferase is part of the so-called liver tests – studies that diagnose disorders in the liver. The liver is a vital organ located in the upper right side of the abdomen. It is involved in many important bodily functions—helping with nutrient processing, bile production, the synthesis of many important proteins such as blood clotting factors, and the breakdown of potentially toxic compounds into harmless substances. A number of diseases lead to damage to liver cells, which increases the activity of aspartate aminotransferase. The most common test for aspartate aminotransferase is prescribed to check if the liver is damaged due to hepatitis, toxic drugs, cirrhosis. However, AST does not always reflect only liver damage; the activity of this enzyme can also increase in diseases of other organs, in particular, in myocardial infarction.

What is the test for

To detect liver damage. Usually, an AST test is ordered along with an alanine aminotransferase (ALT) test or as part of a general liver function test. AST and ALT are considered the two most important indicators of liver damage, although ALT is more specific than AST. In some cases, AST is directly compared to ALT and their ratio (AST to ALT) is calculated. It can be used to find out the causes of liver damage. The AST blood count is often compared with the results of other tests, such as alkaline phosphatase (ALP), total protein, and bilirubin, to determine the specific form of liver disease. The assay is designed to monitor the effectiveness of treatment for liver disease and to monitor the health of patients taking potentially liver-toxic drugs. If AST activity rises, the patient may be switched to other medications.

Test method

UV kinetic.

Study biomaterial

Blood (serum).

How to properly prepare for the exam

On an empty stomach (8-12 hours of fasting), fasting for 3-4 hours is possible for children under two years of age.
For a day, exclude physical and emotional stress, overheating and hypothermia, sleep disturbance, air travel, instrumental research methods (ultrasound, X-ray, etc.), physiotherapy, massage, alcohol and medication (the latter – only by agreement with the doctor! ).
If it is not possible to refuse the medication, please inform the laboratory when ordering.
Do not smoke one hour before blood sampling.
A small amount of water is allowed on the day of the test.
Before manipulation, you should take a comfortable position, relax and calm down.

What can influence the result?

Raise levels:

Drugs that cause cholestasis: aminosalicylic acid, anabolic steroids, benzodiazepines, carbamazepine, etc.;
Hepatotoxic drugs: anti-tuberculosis, antiarrhythmic, antifungal, antithrombotic drugs, antidepressants, anabolic steroids, antibiotics, NSAIDs, hypoglycemic drugs, oral contraceptives, analgesics and antipyretics, inhibitors. 3-methylglutaryl A-reductase.

Reduce levels:

Drugs: antibacterials, vitamins (ascorbic acid), uric acid suppressants, immunosuppressants, NSAIDs, female sex hormones and their synthetic analogues.

Synonyms

Glutamine-oxaloacetate transaminase in blood serum, glutamate-oxaloacetate transaminase in blood serosa (SGOT), aspartate transaminase, AST/ALT spontaneous activity. Serum glutamine-oxaloacetic transaminase, serum glutamate-oxaloacetate transaminase (SGOT), aspartate transaminase, AST/ALT ratio. Aspartate aminotransferase.

What do the results mean? Reference values

Men up to 50.0 U/L.
Women up to 35.0 U/L.
Neonates: 25.0–75.0 U/L.
Children under 36 U/L.

Normally, AST activity in the blood is low. Excessively high AST activity (more than 10 times normal) is usually caused by viral infections. It can also increase significantly due to medications or other substances that are toxic to the liver, as well as due to diseases that slow down blood flow to the liver (ischemia). In chronic hepatitis, AST activity usually exceeds the norm by no more than 4 times. It fluctuates between normal and somewhat elevated, so often an analysis is prescribed to determine the degree of the disease. Diseases such as obstruction of the biliary tract, cirrhosis, and some types of liver cancer contribute to a moderate increase in AST. After a heart attack and with muscle damage, AST activity can also increase, usually much more than ALT. In most liver diseases, ALT activity in the blood is higher than AST activity, so the ratio of AST to ALT will be low. However, there are a few exceptions: alcoholic hepatitis, cirrhosis, and muscle damage.

Who orders the examination?

Therapist, cardiologist, hepatologist, gastroenterologist, general practitioner, surgeon, pediatrician.

Alanine aminotransferase (ALT, ALT): norm and interpretation

Alanine aminotransferase (ALT, ALT) is an enzyme involved in biochemical processes inside cells. ALT catalyses the transfer of amino groups. In small amounts ALT is found in many tissues of the body. In the heart muscle, its content is much less than aspartate aminotransferase (AST, AST) . The highest concentrations of ALT are found in the liver, approximately 3000 times higher than in blood serum. Therefore, the measurement of the content of aspartate aminotransferase is primarily used in the diagnosis of liver diseases. In case of damage to liver cells of various origins, ALT is released, which enters the blood serum. Alanine aminotransferase entering the blood is processed in the liver, and the half-life is 47 ± 10 hours, which significantly exceeds the half-life of AST (17 ± 5 hours).

Physicians who specialize in patients with liver disease, primarily hepatologists and gastroenterologists, recognize the importance of measuring the activity of hepatic aminotransferase enzymes, including ALT (ALT) and AST (AST) in the diagnosis and evaluation of liver disease. The activity of alanine aminotransferase ALT in blood serum has been considered for many decades as a reliable and sensitive indicator of liver diseases. In addition, ALT is a qualitative marker of general health, especially for patients suffering from obesity, metabolic syndrome and cardiovascular disease, as they have a high risk of getting sick non-alcoholic fatty liver disease . This group of diseases affects from 12 to 35% of the adult population in developed countries, and among obese patients up to 80% suffer from non-alcoholic fatty liver disease (NAFLD). A severe form of NFLD, called steatohepatosis, is diagnosed in 2-5% of the total population of the planet.

Despite these alarming statistics, slight increases in blood levels of ALT are often ignored by physicians, given that non-alcoholic fatty liver disease, viral hepatitis, and other liver damage often occur without significant symptoms. In 2008 The American Association for the Study of Liver Diseases (AASLD) has issued a white paper emphasizing the importance of blood measurements of alanine aminotransferase ( ALT ) in determining levels of general health, liver health, and diagnosing liver disease. The purpose of this paper was to confirm that ALT not only remains an important, inexpensive, and reliable medical test, but is also a population screening tool for early detection of liver disease.

The need for detailed evaluation of patients with elevated levels of ALT depends on the results of the anamnesis and physical examination, the duration of the increase in the level of ALT and its concentration. One study from Scandinavia, which included 151 patients with mild to moderate increases in serum aminotransferase for at least 6 months, showed the prevalence of liver disease in this group of subjects. Diagnoses included non-alcoholic steatohepatitis and hepatic steatosis (42%), chronic hepatitis C (15%), alcoholic liver disease (8%) and autoimmune hepatitis, primary biliary cirrhosis, and alpha-1 antitrypsin deficiency.

Norm ALT for children and adolescents is somewhat different from the norm for adults:

9013 7 to 39.0

Age	A content LT, U/l
0–5 days	up to 49 . 0
5 days – 6 months	up to 56.0
6-12 months	up to 54.0
1-3 years	up to 33.0
3-6 years	up to 29.0
6-12 years
12–17 years (women )	up to 24.0
12–17 years old (men)	up to 27.0

Increase in myocardial infarction ALT 9 0074 in blood serum is detected in 50-70% of cases, more often with extensive damage to the heart muscle. The largest increase in concentration alanine aminotransferase is detected in the acute phase of a heart attack – an average of 2.5 times higher than normal, which is noticeably inferior to an increase in the content of aspartate aminotransferase – about 5-6 times higher than normal.

In liver diseases, the activity of ALT changes first and most significantly (compared to AST ). In acute hepatitis, regardless of its nature, the activity of ALT and AST increases in all patients. But the content of ALT , therefore, its definition is a more sensitive test for the early diagnosis of acute hepatitis than AST .

In acute liver tissue damage, the level of AST usually increases immediately and immediately reaches higher values than ALT . This is due to the greater activity of AST in liver cells. However, after 24-48 hours, especially if the pathological process continues to injure the liver, the level of ALT will become higher than AST , which is explained by its long half-life. In chronic diseases of the liver tissue ALT is more often elevated than AST ; however, as soon as fibrosis develops, the activity of ALT usually decreases, and the ratio of AST to ALT gradually increases, so that in patients with cirrhosis of the liver AST often exceeds ALT . An exception for chronic diseases are alcoholic liver diseases, which are characterized by a predominance of AST over ALT at all stages.

Non-alcoholic fatty liver disease (NAFLD) is probably the most common cause of elevated blood levels of ALT in adults. Risk factors for NZhZP include obesity, diabetes, and hyperlipidemia. For this large group of patients, testing for ALT contributes to the timely diagnosis of NAFLD, even before the disease progresses to the stage of deadly irreversible liver fibrosis. Increased activity ALT may be the only marker for the development of this disease. Elevated levels of ALT correlate with the severity of NFLD. In a study in which 233 obese women were examined, 60% had initial liver fibrosis, and most of these patients had elevated levels of ALT . 28% of patients with mild fibrosis and 68% of patients with advanced fibrosis show increased levels of ALT , while in patients without fibrosis, concentrations of ALT were increased only in 17% of cases. Thus, ALT is an excellent test for the detection of non-alcoholic fatty liver disease.

For alcoholic liver diseases, an increase in the level of AST is more characteristic, although a slight increase in the content of ALT is common to all patients. In the case of chronic hepatitis C virus infection, ALT levels and levels may remain normal. However, sometimes the detection of an elevated level of ALT leads to a further diagnosis of chronic hepatitis C. Thus, among 248 blood donors who were diagnosed with chronic hepatitis C, 69% had an increased concentration of ALT in the blood. Thus, the ALT assay itself may not detect a patient infected with the hepatitis C virus, but it is effective in detecting patients with severe liver damage from this disease. The same applies to the diagnosis of chronic liver disease caused by the hepatitis B virus.

ALT and AST levels rise 10-15 days before the onset of jaundice in hepatitis A, and many weeks before the onset of jaundice in hepatitis B (their concentration increases simultaneously, but ALT to a much greater extent). In a typical course of viral hepatitis, the content of ALT reaches a maximum at the 2nd–3rd week of the disease. With a favorable course of the disease, the content of ALT normalizes after 30-40 days, AST – after 25-35 days.

Except as noted, ALT is indicated for suspected liver damage from drugs such as popular non-steroidal anti-inflammatory drugs.

There is a de Ritis coefficient, that is, the ratio AST / ALT , normally equal to 1.33 . In liver diseases, the de Ritis coefficient is below normal, and in heart diseases it is higher. In the acute period of viral hepatitis in all forms, except for severe, the de Ritis coefficient is in the range of 0.55-0.65, with a severe course of the disease, this coefficient averages 0.83.

While ALT is a useful test in the detection of liver disease, new evidence points to its potential value as a measure of overall health and survival.