What are ALT and AST. How are liver function tests performed. What do normal and abnormal results indicate. When should liver function tests be done. How to interpret AST:ALT ratio.

Understanding Liver Function Tests: ALT and AST Explained

Liver function tests are crucial diagnostic tools used to assess the health and functionality of the liver. Among these tests, Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) are two key enzymes that play a significant role in evaluating liver health. These enzymes, when found in elevated levels in the blood, can indicate liver damage or inflammation.

What is ALT?

ALT, formerly known as Serum Glutamic Pyruvic Transaminase (SGPT), is an enzyme primarily found in the liver and kidneys. It catalyzes the transfer of an amino group from alanine to α-ketoglutarate, producing pyruvate and glutamate. This process is reversible and can be represented by the following formula:

glutamate + pyruvate ⇌ α-ketoglutarate + alanine

Under normal circumstances, ALT levels in the blood are low. However, when liver cells are damaged, ALT is released into the bloodstream, causing elevated levels that can be detected through blood tests.

What is AST?

AST, previously referred to as Serum Glutamic Oxaloacetic Transaminase (SGOT), is another enzyme found in various organs, including the liver, heart, muscles, and kidneys. While it is also used to assess liver function, it is less specific to liver damage compared to ALT, as elevated AST levels can indicate damage to other organs as well.

The Importance of ALT and AST in Liver Function Assessment

ALT and AST are often measured together as part of a comprehensive liver function panel. These enzymes serve as valuable biomarkers for liver health due to their specific characteristics:

• ALT is more liver-specific and has a longer half-life, making it a more reliable indicator of liver damage.
• AST is found in multiple organs, providing a broader perspective on potential organ damage.
• The ratio of AST to ALT (known as the De Ritis ratio) can offer insights into the nature and cause of liver damage.

By analyzing these enzymes, healthcare professionals can gain crucial information about liver health and function, helping them diagnose and monitor various liver conditions.

Normal and Abnormal ALT AST Ranges: What Do They Mean?

Understanding the normal and abnormal ranges for ALT and AST is essential for interpreting liver function test results accurately. While specific reference ranges may vary slightly between laboratories, general guidelines can help in interpreting these values.

Normal ALT AST Ranges

Typically, normal ALT and AST levels fall within the following ranges:

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

It’s important to note that these ranges can differ based on factors such as age, gender, and the specific testing methods used by laboratories.

Abnormal ALT AST Ranges

Elevated levels of ALT and AST can indicate various liver issues:

• Mild elevation (2-3 times the upper limit of normal): May suggest mild liver damage or inflammation
• Moderate elevation (3-20 times the upper limit of normal): Often indicates more significant liver damage, such as viral hepatitis or drug-induced liver injury
• Severe elevation (>20 times the upper limit of normal): Typically suggests severe liver damage, such as acute viral hepatitis or toxin-induced liver injury

Is it possible to have low ALT and AST levels? While less common, low levels of these enzymes can occur and may indicate conditions such as vitamin B6 deficiency or severe liver damage in advanced cirrhosis.

Interpreting the AST:ALT Ratio (De Ritis Ratio)

The AST:ALT ratio, also known as the De Ritis ratio, can provide valuable insights into the nature of liver damage. How is this ratio interpreted?

• AST:ALT ratio < 1: Typically seen in viral hepatitis and other forms of acute liver injury
• AST:ALT ratio > 2: Often indicative of alcohol-induced liver disease
• AST:ALT ratio between 1 and 2: May suggest various liver conditions and requires further investigation

Why is the AST:ALT ratio useful in diagnosing alcohol-induced liver disease? Alcohol consumption tends to affect AST levels more significantly than ALT levels, leading to a higher ratio in cases of alcohol-related liver damage.

When Should Liver Function Tests Be Performed?

Liver function tests, including ALT and AST measurements, are recommended in various scenarios to assess liver health and function. When might a healthcare provider order these tests?

• Suspected liver disease: In cases where symptoms such as jaundice, fatigue, nausea, vomiting, dark urine, or pale stools are present
• Monitoring liver function: For patients taking potentially hepatotoxic medications or those with chronic liver conditions
• Screening for liver disease: In individuals with risk factors such as alcohol abuse, family history of liver disease, or exposure to hepatitis viruses
• Evaluating treatment efficacy: To assess the effectiveness of treatments for liver conditions, including hepatitis C

How frequently should liver function tests be performed in patients with chronic liver conditions? The frequency of testing depends on the specific condition and its severity, but it typically ranges from every 3 to 12 months, as determined by the healthcare provider.

Other Important Liver Function Tests

While ALT and AST are crucial components of liver function assessment, they are often part of a broader panel of tests. What other tests are commonly included in liver function panels?

• Bilirubin: Measures the level of a waste product produced by the breakdown of red blood cells
• Albumin: Assesses the liver’s ability to produce this important protein
• Total serum protein: Evaluates overall protein levels in the blood
• Alkaline phosphatase (AP): Can indicate blockage of bile ducts or certain types of liver damage

How do these additional tests complement ALT and AST in assessing liver function? Each test provides unique information about different aspects of liver health, allowing for a more comprehensive evaluation of liver function and potential issues.

Factors Affecting ALT and AST Levels

While elevated ALT and AST levels often indicate liver problems, it’s important to consider other factors that can influence these enzyme levels. What external factors can affect ALT and AST measurements?

• Medication: Certain drugs, including some antibiotics and pain relievers, can temporarily elevate liver enzymes
• Exercise: Intense physical activity can cause a transient increase in ALT and AST levels
• Alcohol consumption: Even moderate alcohol intake can affect liver enzyme levels
• Obesity: Excess body weight can lead to fatty liver disease and elevated liver enzymes
• Vitamin B6 deficiency: Can result in decreased ALT levels

How should healthcare providers account for these factors when interpreting liver function test results? It’s crucial to consider a patient’s medical history, lifestyle factors, and recent activities when analyzing ALT and AST levels to ensure accurate interpretation and avoid misdiagnosis.

Preparing for Liver Function Tests

Proper preparation is essential for obtaining accurate liver function test results. What steps should patients take before undergoing these tests?

• Fasting: In most cases, patients are advised to fast for 8-12 hours before the test
• Medication review: Inform the healthcare provider about all current medications, as some may need to be temporarily discontinued
• Alcohol abstinence: Avoid alcohol consumption for at least 24 hours before the test
• Hydration: Drink plenty of water (unless otherwise instructed) to ensure proper hydration

Are there any specific precautions for patients with certain medical conditions? Patients with diabetes or other conditions that require regular medication should consult their healthcare provider for specific instructions regarding fasting and medication management before the test.

The Testing Process

Understanding the liver function testing process can help alleviate patient anxiety and ensure smooth test administration. How are liver function tests typically performed?

1. A healthcare professional will clean the skin at the site where blood will be drawn, usually from a vein in the arm.
2. A needle is inserted into the vein to collect a blood sample.
3. The blood is drawn into one or more vials for analysis.
4. Pressure is applied to the puncture site to stop bleeding, and a bandage is applied.
5. The blood sample is sent to a laboratory for analysis.

How long does it take to receive liver function test results? Results are typically available within 24 to 72 hours, depending on the laboratory and the specific tests performed.

Interpreting Liver Function Test Results

Accurate interpretation of liver function test results is crucial for proper diagnosis and treatment. How should healthcare providers approach result interpretation?

• Consider individual reference ranges: As ranges can vary between laboratories, results should be compared to the specific reference ranges provided.
• Evaluate all test components: Look at the entire panel of liver function tests, not just ALT and AST in isolation.
• Assess the degree of elevation: Mild, moderate, or severe elevations can indicate different types and severities of liver issues.
• Consider the AST:ALT ratio: This can provide insights into the nature of liver damage.
• Account for patient factors: Age, gender, medical history, and lifestyle factors should be taken into consideration.
• Look for patterns over time: Serial measurements can be more informative than a single test result.

What should patients do if their liver function test results are abnormal? It’s important not to panic, as abnormal results don’t always indicate severe liver disease. Patients should discuss their results with their healthcare provider, who may recommend further testing or monitoring to determine the underlying cause and appropriate course of action.

Common Causes of Elevated Liver Enzymes

Elevated ALT and AST levels can be caused by various factors, ranging from temporary issues to serious liver conditions. What are some common causes of elevated liver enzymes?

• Viral hepatitis (A, B, C)
• Alcoholic liver disease
• Nonalcoholic fatty liver disease (NAFLD)
• Drug-induced liver injury
• Autoimmune hepatitis
• Hemochromatosis
• Wilson’s disease
• Liver cancer
• Cirrhosis

How do healthcare providers determine the specific cause of elevated liver enzymes? Additional tests, such as viral hepatitis panels, imaging studies, or liver biopsies, may be necessary to pinpoint the underlying cause and guide appropriate treatment.

Treatment and Management of Liver Enzyme Abnormalities

The approach to treating and managing abnormal liver enzyme levels depends on the underlying cause and severity of the condition. What are some general strategies for addressing elevated ALT and AST levels?

• Lifestyle modifications: Reducing alcohol consumption, maintaining a healthy weight, and following a balanced diet
• Medication management: Adjusting or discontinuing medications that may be causing liver damage
• Treating underlying conditions: Addressing viral hepatitis, autoimmune disorders, or other specific causes
• Regular monitoring: Periodic liver function tests to track progress and adjust treatment as needed
• Liver-protective medications: In some cases, medications to support liver health may be prescribed

Can elevated liver enzymes return to normal levels? In many cases, with proper treatment and lifestyle changes, liver enzyme levels can improve and even return to normal ranges. However, the timeline for improvement varies depending on the underlying cause and the individual’s response to treatment.

Preventing Liver Damage

While some liver conditions are unavoidable, many cases of liver damage can be prevented through lifestyle choices and proactive health measures. How can individuals reduce their risk of liver damage and maintain healthy ALT and AST levels?

• Limit alcohol consumption: Follow recommended guidelines for moderate drinking or abstain completely
• Maintain a healthy weight: Obesity is a significant risk factor for nonalcoholic fatty liver disease
• Exercise regularly: Physical activity helps maintain liver health and overall well-being
• Practice safe sex and avoid sharing needles: This reduces the risk of contracting viral hepatitis
• Use medications responsibly: Follow prescribed dosages and avoid mixing medications with alcohol
• Get vaccinated: Hepatitis A and B vaccines can prevent these forms of viral hepatitis
• Eat a balanced diet: Focus on whole foods, fruits, vegetables, and lean proteins

How often should individuals without known liver issues have their liver function tested? While there’s no universal recommendation, adults over 45 or those with risk factors may benefit from periodic liver function tests as part of their routine health check-ups. Consult with a healthcare provider to determine the appropriate screening schedule based on individual risk factors and overall health status.

The Future of Liver Function Testing

As medical science advances, new technologies and methodologies are emerging to enhance liver function assessment. What innovations are on the horizon for liver function testing?

• Non-invasive imaging techniques: Advanced ultrasound and MRI technologies for assessing liver fibrosis and fatty liver disease
• Biomarker discovery: Identification of new, more specific markers for various liver conditions
• Genetic testing: Improved understanding of genetic factors influencing liver health and disease susceptibility
• Point-of-care testing: Development of rapid, on-site liver function tests for quicker diagnosis and monitoring
• Artificial intelligence: Integration of AI algorithms to enhance interpretation of liver function test results and imaging studies

How might these advancements impact the diagnosis and management of liver diseases? These innovations have the potential to improve early detection of liver issues, enhance the accuracy of diagnoses, and allow for more personalized treatment approaches, ultimately leading to better outcomes for patients with liver conditions.

The Role of Liver Function Tests in Precision Medicine

As the field of precision medicine grows, liver function tests are playing an increasingly important role in tailoring treatments to individual patients. How are ALT, AST, and other liver function tests contributing to personalized healthcare?

• Predicting treatment responses: Liver enzyme levels can help determine how a patient might respond to certain medications
• Monitoring drug efficacy: Regular liver function tests can assess the effectiveness of treatments for liver conditions
• Identifying at-risk populations: Genetic factors influencing liver enzyme levels can help identify individuals at higher risk for certain liver diseases
• Guiding lifestyle interventions: Personalized recommendations based on liver function test results can help prevent or manage liver issues

Liver Function Tests | Michigan Medicine

Test Overview

Some blood tests are used to determine whether your liver is damaged or inflamed. Although these tests help your doctor evaluate how well your liver is working, they cannot tell if you have hepatitis C.

Tests that assess liver function

Your doctor may do tests to measure certain chemicals produced by the liver. These tests can help your doctor check how well your liver is working.

Tests may measure:

• Bilirubin.
• Albumin.
• Total serum protein.

Tests that check for inflammation of the liver (liver enzyme studies)

Your liver may be damaged if you have increased levels of:

• Alanine aminotransferase (ALT or SGPT).
• Aspartate aminotransferase (AST or SGOT).

An increased level of alkaline phosphatase (AP) may indicate blockage of bile ducts.

Why It Is Done

Liver tests are done when a medical history or physical exam suggests that something may be wrong with your liver.

These tests can also help diagnose long-term (chronic) infection. If liver enzymes are high, a test for hepatitis C antibodies may be done to see if you have hepatitis C.

If you are being treated with antiviral therapy, you may have liver tests from time to time to see whether treatment is working.

How To Prepare

In general, there’s nothing you have to do before this test, unless your doctor tells you to.

How It Is Done

A health professional uses a needle to take a blood sample, usually from the arm.

Results

Normal

All levels are within the normal range.

Abnormal

One or more levels are outside the normal range. Abnormal liver function tests may mean that your liver is inflamed or is not working normally. This can be a sign that you have a viral infection.

Credits

Current as of:
September 23, 2020

Author: Healthwise Staff
Medical Review:
E. Gregory Thompson MD – Internal Medicine
Adam Husney MD – Family Medicine
Martin J. Gabica MD – Family Medicine
W. Thomas London MD – Hepatology

Current as of: September 23, 2020

Author:
Healthwise Staff

Medical Review:E. Gregory Thompson MD – Internal Medicine & Adam Husney MD – Family Medicine & Martin J. Gabica MD – Family Medicine & W. Thomas London MD – Hepatology

Reference Range, Interpretations, Collection and Panels

Description

ALT is an enzyme found primarily in the liver and kidney. It was originally referred to as serum glutamic pyruvic transaminase (SGPT). Normally, a low level of ALT is found in the serum. ALT is increased with liver damage and is used to screen for and/or monitor liver disease.

Alanine aminotransferase (ALT) is usually measured concurrently with AST as part of a liver function panel to determine the source of organ damage. ALT is more specific for liver damage since it is found primarily in the liver and has a longer half-life, whereas AST is found in many other organs. Liver diseases in which AST is higher than ALT include alcohol-induced liver damage, cirrhosis, and liver tumors. ALT catalyzes the transfer of an amino group from alanine to a-ketoglutarate, the products of this reversible transamination reaction being pyruvate and glutamate, as seen in the formula below:

• glutamate + pyruvate ⇌ α-ketoglutarate + alanine

Of note, synthesis of ALT is dependent on vitamin B6 (pyridoxal phosphate) and will be decreased in the setting of low vitamin B6 and cirrhosis.

Indications/Applications

When liver disease is suspected (ie, jaundice, fatigue, nausea, vomiting, dark urine, pale colored stools, itching, ascites, mental changes, history of alcohol abuse, suspected acetaminophen overdose, family history of liver disease, exposure to hepatitis viruses)

To monitor liver function (ie, use of potentially hepatotoxic drugs, treatment of or status of chronic liver disease, hepatitis, alcohol-induced liver disease, cirrhosis, fatty liver disease, hepatic failure, Wilson’s disease, hemochromatosis)

Considerations

The AST:ALT ratio (De Ritis ratio) can be used to determine alcohol-induced liver disease, with AST:ALT ratio greater than 2.

Elevated AST and normal ALT can indicate a normal liver but damage to other organs and/or hemolysis.

Both AST and ALT are dependent on vitamin B6 (pyridoxal phosphate). Assays for AST and ALT assume adequate levels of vitamin B6 to accurately measure AST and ALT levels. Vitamin B6 depletion can result in artificially low AST and ALT levels.

Hemolyzed specimens should not be used.

ALT should be run the day of collection since activity is lost at room temperature, 4 º C, and -25 º C.

AST:ALT Ratio

Enzymes are here and there but they shouldn’t be everywhere!

Part 2: AST:ALT Ratio

By Dicken Weatherby, N.D. and Beth Ellen DiLuglio, MS, RDN, LDN

In part 1 of this 2-part article we discussed ALT:AST ratio. In this article we will be talking about the reciprocal ratio, the AST:ALT Ratio also known as the DeRitis Ratio.

AST:ALT ratio

On the flipside… the ratio of AST to ALT, called the De Ritis ratio, can be calculated to monitor progression and severity of liver disease, and can also be used in the assessment of metabolic syndrome, muscle damage, and biliary obstruction. The AST:ALT ratio may become elevated over 1 in cirrhosis, muscle damage, biliary obstruction, and Wilson’s disease. [i] [ii] [iii] [iv] [v]

Liver disease

The AST:ALT ratio can assist in grading severity of pathology in chronic liver disease including alcoholic liver disease and chronic hepatitis. Increasing elevation of the AST:ALT ratio occurs as scarring and fibrosis progress due to tissue damage. An increasing ratio of AST to ALT above 1 is associated with progressive impairment of liver function and associated complications such as cirrhosis.[vi]  Pharmaceutical drugs can cause liver damage as well, which in turn will be associated with an elevated AST:ALT ratio.

Liver detoxification and biotransformation is crucial to minimizing the toxic load on the body; it can be measured using the monoethylglycinexylidide (MEGX) test. Researchers observed an inverse correlation between MEGX results and AST:ALT ratio. MEGX values were significantly lower in those with an AST:ALT ratio of 1 or more, indicating impaired detoxification abilities.[vii]

In liver fibrosis, the AST:ALT ratio is especially useful because it can identify fibrosis even when both AST and ALT are within normal lab range. When the AST:ALT ratio rises above 1, fibrosis can be suspected, indicating that all is not normal.[viii]

Non-alcoholic fatty liver disease (NAFLD) without fibrosis or cirrhosis may be associated with an AST:ALT ratio below 1. The AST:ALT ratio is incorporated into a comprehensive NAFLD fibrosis score. A ratio of less than one is suggestive of NAFLD/non-alcoholic steatohepatitis. However, the ratio rises above 1 in 92% of alcoholic liver disease and climbs above 2 in 70% of cases.[ix]

Chronic hepatitis C without fibrosis is usually associated with an AST/ALT ratio less than 1.[x] However, in the event of fulminant acute viral hepatitis, AST may rise above ALT. In alcoholic hepatitis, AST is usually higher than ALT unless several days have passed without alcohol exposure at which time ALT may rise above AST. An increasing AST:ALT ratio in either condition may be a sign that long-term complications such as fibrosis and cirrhosis are occurring.[xi]

Alcohol abuse

Alcohol is intrinsically damaging to the liver and long-term consumption is associated with increased AST:ALT ratio once liver damage has set in. An AST:ALT ratio of 1.1 or less may be seen with alcohol abuse without cirrhosis. However, long-term alcohol abuse with cirrhosis was associated with an AST:ALT ratio of greater than 1.1. [xii]

In alcoholics with elevated aminotransferases, the mean AST:ALT ratio was 1.5 while for those with normal levels of individual aminotransferases, the ratio was 1.64.[xiii]  With advanced alcohol abuse the ratio is often 2 or above.[xiv] The ratio may increase due to liver fibrosis or reduced clearance of AST by specialized liver cells called sinusoidal cells. [xv] Both AST and ALT enzymes require pyridoxal-5’-phosphate (vitamin B6) and its depletion, common in alcohol abuse, can reduce their levels, especially ALT.

Primary biliary cirrhosis (PBC) is characterized by portal inflammation and destruction of intrahepatic bile ducts and severity may be reflected in the ratio of AST to ALT. A statistically significant correlation was found between advanced PBC and increasing AST:ALT ratio. [xvi]

Biliary obstruction may cause an AST:ALT ratio of greater than 1.5 which suggests that intrahepatic cholestasis is likely. An AST/ALT ratio of less than 1.5 suggests extrahepatic obstruction.[xvii]

Muscle damage

An increasing AST:ALT ratio will be seen in muscle damage, as AST in muscle is significantly higher than ALT. The ratio is helpful in assessing critical limb ischemia (CLI), a form of peripheral artery disease disorder marked by severe obstruction of arteries in the extremities. An AST:ALT ratio of greater than 1.67 suggests a high risk of CLI.[xviii] An elevation of AST can be seen in myocardial infarction and calculation of the AST:ALT ratio may be helpful in assessing severity of cardiac muscle damage.[xix]

Metabolic syndrome risk factors such as waist circumference and waist-to-hip ratio, BMI, diastolic blood pressure, triglyceride levels, LDL, uric acid, fasting insulin levels, and insulin resistance were negatively correlated with ratio of AST to ALT in a random sample of 935 students ages 11-16. Researchers found that there was 6-fold greater risk of metabolic syndrome in those with the lowest AST:ALT ratios and central obesity was the most closely associated factor.[xx] A multicenter observational study of 1,625 adults confirmed that risk of metabolic syndrome was greatest in those with the lowest AST:ALT ratios.[xxi]

So, as you can see, elevated levels of AST and ALT and their ratio relationship can provide valuable clinical data.

Condition	AST:ALT ratio
NAFLD in at-risk patients without liver fibrosis or cirrhosis	Less than 1
Liver fibrosis	1 or greater
Alcohol abuse without cirrhosis	1.1 or less
Alcohol abuse with cirrhosis	Greater than 1.1
Biliary obstruction, intrahepatic	Greater than 1.5
Biliary obstruction, extrahepatic	Less than 1. 5
Critical limb ischemia in peripheral artery disease	Greater than 1.67
Advancing cirrhosis	Greater than 2
Advanced alcoholic liver disease	Greater than 3

Calculating The Ratio – Let ODX Do the Work!

Good news! The AST:ALT ratio is now being automatically calculated by the Optimal DX software if both the AST and ALT are added into the system. No need to do any conversions as the software will do this for you and will now show the result in the Blood Test Results Report:

However, if you simply want to do the calculation manually then please follow these instructions:

The AST:ALT ratio is calculated by dividing the AST result by the ALT result.

Here’s an example:

AST is 26 and the ALT is 22: 26 / 22 = 1.18
So, the AST:ALT Ratio in this example is 1.18

References

[i] Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014 Jan;98(1):1-16.

[ii] Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr. 2007 Jul;74(7):663-71. Review. PubMed PMID: 17699976. [R]

[iii] Rief P, Pichler M, Raggam R, et al. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. Medicine (Baltimore). 2016 Jun;95(24):e3843. [R]

[iv] Hall P, Cash J. What is the real function of the liver ‘function’ tests? Ulster Med J. 2012 Jan;81(1):30-6. [R]

[v] Gowda S, Desai PB, Hull VV, et al. A review on laboratory liver function tests. Pan Afr Med J. 2009 Nov 22;3:17. [R]

[vi] Woreta TA, Alqahtani SA. Evaluation of abnormal liver tests. Med Clin North Am. 2014 Jan;98(1):1-16. [R]

[vii] Giannini E, Risso D, Botta F, et al. Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease. Arch Intern Med. 2003 Jan 27;163(2):218-24. [R]

[viii] Newsome PN, Cramb R, Davison SM, et al. Guidelines on the management of abnormal liver blood tests. Gut. 2018 Jan;67(1):6-19. [R]

[ix] Hall P, Cash J. What is the real function of the liver ‘function’ tests? Ulster Med J. 2012 Jan;81(1):30-6. [R]

[x] Giannini E, Risso D, Botta F, et al. Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease. Arch Intern Med. 2003 Jan 27;163(2):218-24. [R]

[xi] Botros M, Sikaris KA. The de ritis ratio: the test of time. Clin Biochem Rev. 2013 Nov;34(3):117-30. Review. [R]

[xii] Botros M, Sikaris KA. The de ritis ratio: the test of time. Clin Biochem Rev. 2013 Nov;34(3):117-30. Review. [R]

[xiii] Kawachi I, Robinson GM, Stace NH. A combination of raised serum AST:ALT ratio and erythrocyte mean cell volume level detects excessive alcohol consumption. N Z Med J. 1990 Apr 11;103(887):145-8. [R]

[xiv] Lala V, Goyal A, Bansal P, Minter DA. Liver Function Tests. 2020 Mar 27. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.Available from [R]

[xv] Thapa BR, Walia A. Liver function tests and their interpretation. Indian J Pediatr. 2007 Jul;74(7):663-71. Review. [R]

[xvi] Alempijevic T, Krstic M, Jesic R, et al. Biochemical markers for non-invasive assessment of disease stage in patients with primary biliary cirrhosis. World J Gastroenterol. 2009 Feb 7;15(5):591-4. [R]

[xvii] Hall P, Cash J. What is the real function of the liver ‘function’ tests? Ulster Med J. 2012 Jan;81(1):30-6. [R]

[xviii] Rief P, Pichler M, Raggam R, et al. The AST/ALT (De-Ritis) ratio: A novel marker for critical limb ischemia in peripheral arterial occlusive disease patients. Medicine (Baltimore). 2016 Jun;95(24):e3843. doi: 10.1097/MD.0000000000003843. Erratum in: Medicine (Baltimore). 2016 Aug 07;95(31):e5074. [R]

[xix] Rej R. Aminotransferases in disease. Clin Lab Med. 1989 Dec;9(4):667-87. PMID: 2686908. [R]

[xx] Lin S, Tang L, Jiang R, et al. The Relationship Between Aspartate Aminotransferase To Alanine Aminotransferase Ratio And Metabolic Syndrome In Adolescents In Northeast China. Diabetes Metab Syndr Obes. 2019 Nov 18;12:2387-2394[R]

[xxi] Hanley AJ, Williams K, Festa A, et al. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes. 2005 Nov;54(11):3140-7. [R]

Liver injury in COVID-19: clinical features and treatment management | Virology Journal

41.

Huang Y, Zhou H, Yang R, Xu Y, Feng X, Gong P, Clinical characteristics of 36 non-survivors with COVID-19 in Wuhan, China. MedRxiv (2020).

Significance of ALT (Alanine aminotransferase) and AST (Aspartate aminotransferase) as markers of Liver injury

levels greater than 500 IU/L were most frequently observed in people with diseases

that primarily affect hepatocytes such as viral hepatitis, ischemic liver injury, and liver

damage caused by toxins. [4] Increase in aminotransferase is responsible for Viral

hepatitis such as A, B , C , D and E. The increase in ALT involved with hepatitis C

infection where the death of liver cells occurs both by apoptosis and necrosis. Acute

hepatitis is used in the diagnosis of chronic hepatitis when persistence of elevated

ALT for more than six months. [3] [5]

Aspartate aminotransferase (AST): Aspartate aminotransferase is an enzyme found

in muscles, kidney and highest concentration in liver and heart. AST can be released

into blood when the liver is damaged. Normal serum AST value is 0 to 35 IU/L. [6]

Elevated mitochondrial AST seen during myocardial infarction in severe tissue

necrosis, and also in chronic liver diseases such as liver tissue degeneration and

necrosis. The ratio of mitochondrial AST to total AST activity is diagnostically

important in the identification of liver cell necrotic and alcoholic hepatitis conditions. A

study with ALT is also performed along with an AST. These are enzymes contained

in the liver that rise up in the blood when the liver is damaged. A measured AST / ALT

ratio is useful in differentiating various causes of liver injury. [3] [7]

AST/ALT ratio: The AST/ALT ratio increases in liver functional impairment. In

alcoholic liver disease the mean ratio is 1.45, and in post-necrotic liver cirrhosis the

mean ratio is 1.33. Ratio in viral cirrhosis is greater than 1. 17, in alcoholic hepatitis

greater than 2.0 and in non-alcoholic hepatitis greater than 0.9. In Wilson ‘s disease

or hyperthyroidism the ratio is greater than 4.5. [3]

Albumin and total protein: Albumin are proteins made in the liver. Lower than normal

albumin and total protein levels can indicate liver damage or disease. [8] The normal

value for albumin is 3.4 to 5.4 g/dL of blood.

Gamma-glutamyltransferase (GGT): High GGT enzyme levels may point to damage

to the liver or bile duct. [8]

L-lactate dehydrogenase (LD): Elevated levels of LD enzyme may indicate to the

liver damage but can be elevated in many other disorders. [8]

Prothrombin time (PT): This test measures the amount of time it takes to clot the

blood. It may be a sign of liver failure if it takes a long time, cause the liver makes

DRI-CHEM NX500V: Parameters and Specifications

Classification		Parameter	Measuring range				Measurement time (min. )
			Unit (A)		Unit of measurement (B)
Biochemical reaction	Enzymes	Alkaline phosphatase	14-1183	U / L	0.23-19.76	μkat / L	4.
		Amyl nitrite	100-2500	U / L	1.67-41.75	μkat / L	3.
		KFK	10-2000	U / L	0.17-33.40	μkat / L	4.
		GGT	10-1200	U / L	0.17-20.04	μkat / L	5:
		AST	10-1000	units/ l	0.17-16.70	μkat / L	4.
		ALT	10-1000	U / L	0.17-16.70	μkat / L	4.
		Lignin peroxidase	10-1000	U / L	0.17-16.70	μkat / L	5:
		Lactate dehydrogenase	50-900	U / L	0. 84-15.03	μkat / L	2.
	General chemistry	Albumin	1.0-6.0	g / dl	10-60	g / l	6.
		UAC	5.0-140.0	mg / dL	1.79-49.98	mmol / L	4.
		Ca	4.0-16.0	mg / dL	1.00-4.00	mmol / L	4.
		CREB	0.2-24.0	mg / dL	18-2122	μmol / L	5:
		Glutamic acid	10–600	mg / dL	0.6-33.3	mmol / L	6.
		IP	0.5-15.0	mg / dL	0.16-4.84	mmol / L	5:
		Mg	0.2-7.0	mg / dL	0.08-2.88	mmol / L	4.5
		NH 3	10-500	μg / dL	7-357	μmol / L	2.
		Total bilirubin	0.2-30.0	mg / dL	3–513	μmol / L	6.
		TCHO	50-450	mg / dL	1.29-11.64	mmol / L	6.
		TCO 2	5-40	mmol / L	5-40	mmol / L	5:
		Thyroglobulin	10-500	mg / dL	0.11-5.65	mmol / L	4.
		Glyceraldehyde-3-phosphate	2.0-11.0	g / dl	20-110	g / l	6.
		OAM	0.5-18.0	mg / dL	30-1071	μmol / L	4.
	Electrolytes (only on one slide)	Na	75-250	meq / l	75-250	mmol / L	1:
		K	1.0-14.0	meq / l	1. 0-14.0	mmol / L
		CI	50-175	meq / l	50-175	mmol / L
Immunological reaction		vc-SRB	0.3-7.0	mg / dL	3-70	mg / l	5:
Complex S-Panel		Glyceraldehyde-3-phosphate, albumin, alkaline phosphatase, glutamic acid, total bilirubin, immunoprecipitation, TCHO, GGT, ALT, Ca, CREB, OAK
Preoperative S-Panel		Glyceraldehyde-3-phosphate, alkaline phosphatase, glutamic acid, ALT, CREB, OAK
S-panel Plus		Thyroglobulin, lignin peroxidase, AST, amyl nitrite, Mg, Na-K-Cl
Kidney panel		Albumin, glyceraldehyde-3-phosphate, CREB, immunoprecipitation, UAC, Ca
Liver panel		Albumin, glutamic acid, total bilirubin, GGT, alkaline phosphatase, ALT
Horse panel		Lactate dehydrogenase, AST, OAK, Ca, CPK, CREB, albumin, total bilirubin, glyceraldehyde-3-phosphate, glutamic acid, GGT, immunoprecipitation
Calculated parameters		GLOB, albumin / GLOB, OAK / CREB, Na / K, anion difference

Potential use of the growing liver biological set for hepatic recovery after toxic damage (an experimental study)

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“The lack of an acceptable pharmacological solution for the restoration of a damaged liver is due to the complexity of the mechanisms of liver regeneration and the difficulties in choosing a target for exposure. The aim of the study was to study the hepatoprotective function of an extract from a growing and regenerating liver containing a natural set of factors aimed at restoring the organ. Source of extract: regenerating rat liver after 70% resection; and growing liver of a neonatal pig. The extract was obtained according to the original method developed by us, which differs from the method of LaBreque et al. (1975), named it the hepatic regeneration set (HRS). Fractionation of HRS was carried out on Toyopearl HW-50S sorbent. The effectiveness of the action of HRS and fractions was evaluated in a model of toxic liver injury of mice with thioacetamide by the activity of aminotransferases in the blood serum. The activity of AST and ALT in intact animals was 50 and 80 U / L, after the introduction of thioacetamide – 2059 ± 212 and 4280 ± 440 U / L (p <0.05).When using HRS from regenerating rat liver, AST activity was 924 ± 148 U / L (p <0.05), ALT - 1633 ± 308 U / L (p <0.05). When using HRS from the liver of a neonatal piglet, AST activity was 937 ± 138 U / L (p <0.05), ALT - 1710 ± 237 U / L (p <0.05). Two active fractions were isolated, exceeding the effect of the whole extract by 8-29 times. The range of molecular weights of the protein components of active fractions was determined: 3-60 kDa (fraction 1) and 3-25 kDa (fraction 2a). The presence of polynucleotides in the high-molecular fraction was shown.Thus, a technique has been developed for obtaining a natural set of factors obtained from the regenerating and growing liver of model animals, and the effectiveness of their use has been proved on the model of toxic liver damage in the absence of species specificity. The revealed protein and polynucleotide fractions, which significantly exceed the effect of the whole extract, are the basis for further identification of their constituents by methods of immunochromatography, ELISA, MRM mass spectrometry and real-time PCR.”
Reference: Galperin E.I., Ataullakhanov R.I., Dyuzheva T.G., Platonova L.V., Melnikova T.M., Monakov M.Yu., Dudchenko A.M., Lyundup A.V., Klabukov I.D., Possibilities of a biological combination obtained from a growing liver for its restoration in case of toxic damage (experimental study), Biomedical Chemistry, 2017, volume: 63 (5), 440-446

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Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH)

• NAFLD (non-alcoholic fatty liver disease) is the most common liver disease in Western countries. In Finland, 75% of elevated liver enzymes (aged 45-69 years) are associated with NAFLD. In the Russian Federation, the incidence reaches 37%. Approximately 5% of these patients develop steatohepatitis (NASH – non-alcoholic steatohepatitis).
• NAFLD and metabolic syndrome are closely related to each other.
• Fatty liver disease is associated with an increased risk of type 2 diabetes and coronary heart disease.
• The main measures for the treatment of fatty liver disease are lifestyle changes (weight loss, refusal to eat foods and drinks containing “fast” carbohydrates – carbonated drinks, sweets) and control of the results.
• On an outpatient basis, follow-up is necessary to identify patients at risk of developing NASH. If NASH is suspected, a specialist consultation is necessary. In the presence of only fatty degeneration of the liver, there is no need for diagnostic instrumental studies or referral of the patient to a specialist.

Definitions

• NAFLD means
  • or true fatty liver disease (NAFLD) associated with a low risk of developing liver cirrhosis
  • Or NASH (steatohepatitis, 5% of all cases), in which there is damage to liver cells in addition to fatty degeneration.
    • NASH is associated with the risk of progression of liver damage – 10% of patients develop cirrhosis within 10 years.
    • The risk of hepatocellular carcinoma in patients with NASH is higher than in patients with simple steatosis.
    • Diagnostic criteria for NAFLD
      • The presence of fatty degeneration of the liver. Often it is an accidental finding during ultrasound or other instrumental examination (MRI / CT). Instrumental studies solely for the purpose of diagnosing fatty degeneration of the liver are not performed.
      • Alcohol consumption less than 21 g / day. (men), less than 14 g / day. (women)
      • Other causes of fatty liver disease have been excluded.
      • Lack of information on other liver disease (eg, viral hepatitis, autoimmune liver disease)
      • A liver biopsy is required to diagnose NASH. In addition to fatty infiltration, it also allows the detection of balloon dystrophy of hepatocytes. The risk of NASH can be assessed non-invasively using the fibrosis scale.

Examination and diagnosis

With metabolic syndrome

• With metabolic syndrome, fatty degeneration of the liver is often noted, as well as an increased risk of coronary heart disease, type 2 diabetes mellitus, NASH and, in some cases, hepatocellular carcinoma. In patients with metabolic syndrome, the risk of NASH should also be considered and evaluated accordingly.
  • Conduct a NASH risk assessment. The following factors are associated with an increased risk: age; a decrease in the level of platelets or serum albumin (at the lower limit of the normal limit or below it), an increase in AST or ALT activity (at the upper limit of the normal limit or above it)
  • If NASH is suspected, perform the following additional differential diagnostic tests on an outpatient basis: total antibodies to hepatitis A virus (HAV), HBsAg test, antibodies to hepatitis C virus, antigens / antibodies to HIV, serum levels of immunoglobulins IgG, IgM and IgA, antibodies to smooth muscles, antimitochondrial antibodies, antibodies to tissue transglutaminase, plasma iron levels and saturation with transferrin iron, ferritin, TSH, free T4 levels. Follow-up consultation of a gastroenterologist is required to decide whether a liver biopsy is necessary.
  • Ask patient about alcohol use. The simultaneous development of NAFLD and alcoholic fatty degeneration of the liver (AFFD) is possible.
  • If you want to estimate the liver fat content, you can calculate it if you know if the patient has metabolic syndrome and / or type 2 diabetes, and the fasting insulin level, AST and ALT activity are known. in favor of fatty degeneration of the liver. High insulin requirement (above 150 units.) suggests the presence of fatty degeneration of the liver.

In case of accidentally detected fatty degeneration of the liver or increased ALT activity

• Fatty liver disease, accidentally detected during instrumental studies (ultrasound, CT, MRI), or an increase in ALT activity (above 50 U / L and 35 U / L in men and women, respectively) are indications for excluding one of the conditions listed below
  • Metabolic syndrome or risk factors for diabetes
    • Fatty liver disease significantly increases the risk of metabolic syndrome regardless of body mass index or alcohol consumption.
    • Weight loss is particularly important for patients with NAIDD because it reduces both cardiovascular risk and the risk of progression to severe disease (NASH).
    • In most patients with fatty liver, liver enzymes are within the reference range.
    • Persistent elevation of liver enzyme activity is an indication for further examination for the development of NASH, associated with a poorer prognosis than in fatty liver disease.
• NASH (see section on NASH risk assessment above)
• Other causes of increased concentration of liver enzymes (for example, alcohol, drugs, etc.).
  • In Finland, 75% of liver enzyme elevations are associated with NAIDD.
  • Assessment of alcohol consumption using the AUDIT test and laboratory interventional alcohol talk (if necessary)
  • Primary analyzes
    • ALT, alkaline phosphatase, total and conjugated bilirubin, fasting plasma glucose, lipid profile
    • Depending on the results of tests to assess the risk of diabetes mellitus – oral glucose tolerance test
    • Complete blood count, platelet count, thromboplastin time / prothrombin index or INR, serum albumin
    • Ultrasound of the upper floor of the abdominal cavity (if not previously performed)
    • If the activity of liver enzymes persists after exclusion of fast carbohydrates and weight loss (as well as, possibly, exclusion of alcohol, discontinuation of drugs and / or medicinal herbs / dietary supplements with hepatotoxic potential), study antibodies to hepatitis A virus, HBsAg, antibodies to the virus hepatitis C, antigens / antibodies to HIV, immunoglobulins IgG, IgM and IgA, antibodies to smooth muscle, antimitochondrial, antinuclear antibodies, antibodies to tissue transglutaminase, ferrokinetic parameters (iron level, transferrin saturation with iron, ferritin), as well as free TSH and T4 . ..

Treatment

• Weight loss, target 10% per year
• Exclusion of products, in particular those containing fructose as a sweetener (especially harmful to the liver) and fast carbohydrates – soft drinks with sugar, sweets. Reducing your carbohydrate intake should not lead to an increase in saturated fat (such as butter).
• If necessary, exercise for weight loss and bariatric surgery.
• Elimination of alcohol, drugs or medicinal herbs / dietary supplements that promote the accumulation of fat in the liver

Information source:

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Liver function tests-ALT | Sağlam Aile

The most common tests used to check for liver damage are ALT (alanine aminotransferase) and AST (aspartate aminotransferase).

What is ALT?

Alanine aminotransferase (ALT) is an enzyme found primarily in the liver and to a lesser extent in the kidneys and other organs. It plays a role in converting digested nutrients into energy. It is usually found in liver cells and can be found in very small amounts in the blood due to dead liver cells. An excess of ALT in the blood is a major indicator of liver damage. Liver damage can be caused by many diseases. Other tests should be done after treatment planning and analysis of elevated ALT and other liver enzymes before liver failure develops. The higher the level of the enzyme in the blood, the more the liver is damaged.A slight increase can also occur in conditions such as unbalanced and excessively fatty foods, fatty liver.

When should an ALT test be performed?

ALT testing, along with other liver enzymes, can be checked at regular clinic visits if liver disease is suspected. An ALT test is one of the most important reasons to suspect liver disease or damage in the following situations:

• Swelling and pain in the abdomen and stomach
• Nausea, vomiting
• Jaundice
• Fast weight loss
• Constant fatigue
• Unexplained itching of the skin
• Darkening of the color of urine
• Light stool

In addition to the reasons stated above, those who continue to drink alcohol should have more frequent ALT tests for liver damage. In addition, people with a family history of liver disease, hepatitis, or drug use that can cause liver damage should be tested regularly for ALT.

ALT above and below the norm

Normal ALT levels should be in the range of 7-35 U / L in healthy women and 10-50 U / L in men. There is no medical significance or danger of getting a result below these guidelines. That is, if your test results are below normal, there is nothing to worry about.However, if the ALT level is higher than normal, it is necessary to find out the cause. The following are the most common conditions that can lead to elevated ALT levels, meaning liver damage:

• Fatty liver
• Constantly used drugs
• Excessive alcohol consumption
• Excess weight
• Diabetes mellitus
• Cholesterol drugs
• Heart problems
• Hepatitis A, B and C infections
• Cerroz
• In addition to the reasons listed above, people with a family history of liver disease are more likely to develop liver disease than others. To do this, these people need to regularly take liver tests.

For online registration, as well as for other questions, you can also call the information center at (012) 910 or write on Whatsapp at (055) 4000 910.

Scientists from China have estimated the frequency of ALI in patients with COVID-19

A group of researchers from China studied the prevalence of acute liver failure (ALI) in patients with COVID-19, observed in hospitals in different parts of the PRC, follows from the results of a systematic review published in Digestive and Liver Disease.Most patients had minor liver damage from SARS-CoV-2, but those with elevated ALT or AST levels were more likely to need intensive care, they said.

All records related to SARS-CoV-2 published between December 1, 2019 and March 25, 2020 were systematically reviewed by the team. The authors used the authorship criterion to avoid duplication of data. Therefore, the systematic review included studies that provided information on alanine or aspartate aminotransferase (ALT-AST) and / or total bilirubin levels, gastrointestinal (GI) symptoms associated with liver disease, and hospital progression. Acute liver failure (ALI) was defined as an increase in ALT or AST. A total of 26 articles were included in the review, covering 3109 patients. Only 1 study reported serious liver damage and was removed from the review.

The median age of patients was 50 years (interquartile range [IQR], 47–55), the majority of them were men (56.0%). Symptoms of gastrointestinal tract disorders were observed in 6.5% (IQR, 3.0% -11.5%) of patients. Some patients (24.5%; IQR, 17.0% -36%) developed ALI during the follow-up period, while only 2% (IQR, 1.0% -9.2%) had liver disease before this.ALI did not correlate with GI symptoms (correlation coefficient [cc], 0.22) or with liver disease (cc, 0.12).

Most ALI cases were caused by minimally elevated ALT levels (median, 29 U / L; IQR, 24-35 U / L) or increased ALT (median, 33 U / L; IQR, 30-34 U / L) with normal bilirubin levels (median 0.64 mg / dl; IQR 0.57-0.80 mg / dl). Experts have reported a correlation between elevated AST (cc, 0.79) or ALT (cc, 0. 78) with transfer to the intensive care unit (ICU).

One limitation of the review is that the investigators were unable to assess specific trends and make appropriate predictions for each patient with acute liver injury because the mean ALI markers from several studies were used in the final systematic analysis. In addition, all of the studies included in the review were conducted in China, which may also limit the generalizability of the results.

Thus, the study authors concluded that ALI did not correlate with symptoms of gastrointestinal disorders or liver disease, but indicated that patients with elevated ALT or AST levels were more likely to require transfer to the ICU.In most patients, SARS-CoV-2 liver damage was found to be minor.

Effect of high doses of ursodeoxycholic acid on the level of transaminases in patients with hepatitis C

Current treatment of chronic hepatitis C virus infection is based on the use of pegylated interferon alone or in combination with other antiviral agents such as ribavirin or protease inhibitors. However, such treatment has been shown to be insufficiently effective in all patients with hepatitis C virus (HCV) genotype 1 and high levels of this virus in the body, as well as in all patients with liver cirrhosis [1–4].Ursodeoxycholic acid (UDCA) was discovered by Hammarsten in 1902 in polar bear bile, and then Shoda [5] isolated it and isolated it in the form of crystals. Currently, all over the world, UDCA is used to treat primary biliary cirrhosis (PBC) and chronic liver diseases [6–14]. Until 2006, within the framework of the Japanese national health insurance system, a dose of 150 mg / day of UDCA was recommended for standard therapy for hepatoprotection in patients with chronic viral hepatitis.However, this dose is ineffective for the treatment of chronic hepatitis [15]! In a randomized, controlled, multi-dose study of UDCA in chronic hepatitis C (CHC), 600 or 900 mg of this drug was shown to significantly lower plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase. (GGTP) compared to the then recommended dose of 150 mg / day in Japan [16].However, the question of which of the UDCA dosages – 600 or 900 mg / day – is more preferable, required further clarification.

In order to evaluate the effectiveness of UDCA at a dose of 900 mg / day in the treatment of CHC, in the present study the dose of this drug was increased from 600 to 900 mg / day. ALT change was chosen as the primary endpoint of the study.

Materials and research methods

Patients

January to December 2007the study included patients with chronic hepatitis or compensated cirrhosis of the liver due to HCV (mean age 65.8 years, range 43–80 years), who had positive plasma HCV-RNA test results. All included patients were already receiving UDCA at a dose of 600 mg / day for treatment. Within four weeks before increasing the dose of UDCA, they had their ALT levels measured twice – it was above 40 IU / L. Patients were excluded from the study if they received antiviral therapy with interferon with or without ribavirin or anticancer therapy for hepatocellular carcinoma (HCC), had other malignant diseases diagnosed within 24 weeks prior to this study, received treatment with corticosteroids, and / or immunosuppressive drugs, had decompensated cirrhosis, hepatitis B, autoimmune liver diseases, alcoholic or drug damage to the liver, disorders of bile excretion. Patients receiving intravenous glycyrrhizin were included in the study. However, a change in the dose or frequency of administration of glycyrrhizin was regarded as the endpoint of the study. Before enrollment in the study, all patients gave informed written consent to participate in it.

Methods

Patients were followed for 4 weeks after which the dose of UDCA (Urso®, Mitsubishi Tanabe Pharma Corp., Osaka, Japan) was increased from 600 to 900 mg / day.Plasma ALT was assessed as the primary endpoint reflecting liver function, and AST and GGTP as secondary endpoints. The value of these indicators was determined by traditional methods. Blood samples were taken during the observation period and at 0, 4, 8 and 24 weeks after initiation of therapy. At these time points, plasma levels of ALT, AST, GGTP, albumin and total bilirubin were measured, and platelet counts were calculated. Every 12th week or 24th week, screening by computed tomography or ultrasonography for HCC was performed. Compliance with UDCA and the development of complications was assessed by interviewing patients or based on data from their diaries.

Statistical analysis

The significance of changes in the concentration of AST, ALT, GGTP, total bilirubin, albumin and platelet count was assessed using the paired Student’s t-test. Differences were considered significant at p <0.05.

Results

A total of 32 patients were included in the study.Their characteristics are presented in table. 1. Of 7 patients with liver cirrhosis, 5 corresponded to class A, 2 – to class B on the Child scale. In 3 patients with a history of HCC, dynamic computed tomography confirmed complete recovery after performing transcatheter arterial embolization and / or percutaneous radiofrequency ablation 24 weeks or more prior to the start of the present study. Compliance with UDCA treatment was more than 95%.

Change in AST, ALT and GGTP levels with increasing dose of UDCA

Plasma levels of ALT, AST and GGTP before and after administration of 900 mg / day UDCA are shown in Fig. 1. It can be seen that after the appointment of UDCA at this dosage, the level of all three parameters in the blood plasma significantly decreased at 4, 8 and 24 weeks. So, by the 8th week, compared with the initial level, the decrease in ALT was 14.3 IU / L (22.1%), AST – 10.5 IU / L (19.1%), GGTP – 9.8 IU / l (22.1%).

Change in plasma albumin, total bilirubin and platelet count

By the 24th week of treatment with UDCA at a dose of 900 mg / day, the plasma level of albumin changed from 4.0 to 4.1 g / dl, total bilirubin – from 0.76 to 0.73 g / dl, platelet count – from 145 000 / μl to 154,000 / μl.All observed differences did not reach statistical significance (p ≥ 0.05, Fig. 2). Plasma levels of HCV-RNA did not change during the study.

Safety

During treatment with UDCA at a dose of 900 mg / day, there were 3 cases of complications (9.4%): 2 patients developed mild diarrhea, 1 – a feeling of discomfort in the oral cavity. None of these complications affected UDCA treatment compliance. 24 weeks after treatment with an increased dose of UDCA, 1 patient had a relapse of HCC.However, this disease has been completely cured with percutaneous radiofrequency ablation.

Discussion

The results of this study indicate that increasing the dose of UDCA from 600 to 900 mg / day led to an improvement in the biochemical parameters – AST, ALT and GGTP – starting from 1–2 weeks of this therapy regimen. Moreover, the values ​​of biochemical parameters continued to improve until the 24th week of treatment with increased doses of UDCA. In addition, against the background of the therapy, there was a tendency to an increase in the number of platelets.Therefore, the results obtained show that UDCA at a dose of 900 mg / day can improve liver function indicators in patients with chronic hepatitis C who have previously taken UDCA at a dose of 600 mg / day. Within the framework of this study, the incidence of complications from the therapy was lower than in previous studies [15-18]. This may be due to the fact that the patients who took part in the present study already received UDCA, which allowed them to quickly adapt to the higher dose of this drug.

In the natural course of CHC, patients with normal plasma aminotransferase levels are prone to slower progression of fibrosis and a lower incidence of HCC. Rino et al. [19] showed that, in accordance with multivariate analysis data, the therapy regimen (high or low doses) aimed at lowering the parameters, and the level of ALT are the most important factors associated with a decrease in the risk of developing HCC in patients with HCV-related cirrhosis of the class And according to the Child classification, with observation over 10 years.In addition, in one of the previous studies, it was shown that after surgery for HCC, relapses were observed more often among those patients who had higher plasma ALT levels – above 80 IU / L [20]. The IHIT (Suppression of Hepatocarcinogenesis with Interferon Therapy) study found that the risk of HCC after interferon treatment, during which virologic remission was not achieved, strongly depends on the level of ALT. In the same study, it was shown that the odds ratio of developing HCC in patients with persistent virological remission was the same as in patients with persistent remission of biochemical parameters [21].Therefore, high doses of UDCA have the potential to reduce the risk of developing and recurrent HCC by lowering plasma ALT levels.

The anti-inflammatory mechanism of UDCA is associated with a decrease in the cytotoxicity of hydrophobic bile acids, stimulation of hepatobiliary secretion, suppression of NF-kB-dependent transcription by binding to the glucocorticoid receptor, and a decrease in proinflammatory cytokine-induced transcription of phospholipase A2 [22-28].

The long-term effects of UDCA in patients with CHC are not fully understood [29].Changes in liver histology with UDCA treatment may remain unclear at short follow-up periods. In the present study, increasing the dose of UDCA to 900 mg / day for 24 weeks tended to increase the platelet count. As is known, in patients with HCV-related chronic liver diseases, the number of platelets in the blood reflects the histological picture of the liver. In particular, with a low platelet count, progression of hepatic fibrosis should be assumed [30–33].Taking into account the above data, in the future it is necessary to study the effect of UDCA on the histological picture of the liver.

Thus, oral administration of an increased dose – 900 mg / day – of ursodeoxycholic acid, despite the absence of antiviral effect, has a positive effect on reducing the activity of chronic hepatitis and cirrhosis.

First published in World Journal of Gastroenterology,
2009 June 14. – 15 (22). – 2782-2786.

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