ALT liver function test | The London Clinic

You may want to have an ALT liver function test if you drink alcohol quite often, eat a lot of high fat foods, smoke, or have had liver problems in the past.

An ALT blood test is a simple procedure that can quickly tell you if your liver is healthy, or if there are potential problems that may need investigating further.

For some people, having their liver health checked with a simple ALT test can prevent health problems developing and even save their life.

An ALT test requires you to give a blood sample. This is obtained using a needle that’s inserted into a vein in your arm. We can numb your skin beforehand so you don’t feel pain.

It usually takes less than five minutes to collect a blood sample.

Your sample is then tested in our diagnostic laboratory to identify the level of ALT in your blood.

Information about your ALT level is sent back to your consultant hepatologist, usually the same day.

They will then get in touch with you to discuss your result and discuss any next steps.

The main reasons why your levels of ALT may rise include: 

Fatty liver disease

Fatty liver disease is when fat gets stored in your liver cells. This can happen due to eating a high fat diet, drinking a lot of alcohol, eating too much or not getting enough exercise.

If you are overweight, have type 2 diabetes or a raised cholesterol level, you may be at risk of having fat within your liver. 

Drinking too much alcohol

Men who regularly drink more than 21 units of alcohol per week, and women who drink more than 14 units per week, are more likely to have high levels of ALT.

People who regularly drink a lot of alcohol over a short space of time (binge drink) are also at risk of high levels of ALT and damaging their liver cells.

Taking certain medicines

Using more than the recommended amount of certain medicines each day, such as paracetamol, may lead to liver damage.

If you are in pain and paracetamol isn’t helping, speak to your doctor for advice on a stronger painkiller that you can use.

Whenever you start taking a new medicine, check that you take it as your doctor or nurse advises.  

While taking any medicine, look for signs that may mean your liver is being affected, such as yellow skin or yellow eye whites (jaundice).

There are certain conditions that can cause high levels of ALT, including:

Infection by chronic hepatitis viruses

Viral infections such as hepatitis B and hepatitis C can lead to a rise in ALT levels. 

You can get a vaccine against hepatitis B to protect your liver, but not for hepatitis C.

Haemochromatosis

High levels of ALT could be a sign of the genetic liver disease haemochromatosis. 

Haemochromatosis involves iron levels slowly building up in your body over many years.

Autoimmune hepatitis

Autoimmune hepatitis is when your body begins to attack its own liver cells. High levels of ALT can be a sign of this condition.

You can have an ALT liver function test once a year to help monitor any changes in your liver health.

This is particularly recommended for people at high risk of liver disease because of infection, an underlying condition or lifestyle factors.

Tests for Liver Disease | Saint Luke’s Health System

This sheet describes tests that may be
done for liver problems. Your healthcare provider will tell you which tests you need.

Blood tests to check the liver

A small amount of blood may be
taken and tested for one or more of the following:

• AFP (alpha fetoprotein). This is a protein made by the
  liver. A high level in the blood can be a sign of liver cancer or liver injury and
  regeneration in adults.

• Albumin. This is a liver function test. It measures a
  protein made by the liver. When a person has liver disease, the level of albumin
  in the blood (serumalbumin) is often low.

• Alk phos (alkaline phosphatase). This is an enzyme that
  is mostly made in the liver and bones. It’s measured with a blood test. A high
  level suggests a problem with the bile ducts in the liver.

• ALT (alanine aminotransferase). ALT is an enzyme made
  by the liver. When the liver is damaged, ALT leaks into the blood. If a blood test
  finds a high level of ALT, this can be a sign of liver problems such as
  inflammation, scarring, or a tumor.

• AST (aspartate aminotransferase). AST is another enzyme
  made by the liver as well as by other organs such as muscle. It too is measured
  with a blood test. High levels of AST may be a sign of liver injury, especially if
  the ALT level is also high.

• Bilirubin. This is a liver function test. It measures
  the yellow substance made when the body breaks down red blood cells. Bilirubin is
  collected by the liver to be sent out of the body with stool. When something is
  wrong with the liver or bile ducts, bilirubin may build up in the body. This
  causes yellowing of the skin and the whites of the eyes (jaundice). Two
  measurements may be taken from this test:
  total bilirubin and
  direct bilirubin. A high bilirubin level may be the
  result of liver disease or a blockage in the bile ducts. A high indirect bilirubin
  can mean a condition called Gilbert syndrome. Only a small portion of people have
  Gilbert syndrome. Gilbert syndrome is not a sign of disease.  A high indirect
  bilirubin can also be a sign of rapid red blood cell breakdown.

• CBC (complete blood count). This is a test that
  measures all the parts of the blood. These are red blood cells, white blood cells,
  and platelets. Problems with these counts can mean infection or illness. They can
  also be a sign of a problem with the spleen. The spleen is an organ close to the
  liver that can be affected by liver disease. A low platelet count is common with
  advanced fibrosis of the liver. It also happens when the spleen becomes enlarged
  and begins to absorb platelets.

• GGT (gamma-glutamyl transpeptidase). This is a liver
  enzyme that’s often measured along with other enzymes to gauge liver problems. GGT
  is measured with a blood test. If alk phos and GGT are both higher than normal, it
  may be a sign that the bile ducts in the liver may be diseased or blocked. It also
  can be a sign of fatty liver or alcohol damage.

• Glucose. This is a sugar in the blood and the body’s
  most important source of energy. A healthy liver helps the body maintain a normal
  glucose level. If a blood test shows that glucose is low, this may mean the liver
  is not working properly.

• Infectious hepatitis. This is a disease and can be
  found with antibody and antigen tests for hepatitis A, B, C, D, and E. Rarely,
  other viruses like the Epstein-Barr virus (EBV), which causes mononucleosis and
  cytomegalovirus (CMV), can cause hepatitis.

• PT (prothrombin time) or INR (international normalized
  ratio).
  This checks how long it takes for blood to form clots. The liver
  makes a protein that helps with clotting. Problems with clotting can be a sign of
  liver disease.

• 5NT (5′-nucleotidase). This enzyme is made in several
  organs but is only released into the blood by the liver. A high or low level may
  be a sign of liver disease.

• SBA (serum bile acid). This test measures the amount of
  bile acid in the blood. A high level may mean that bile ducts are blocked or that
  the liver is unable to excrete bile acid. This test is rarely done.

• Vitamins A, D, E, and K. These vitamins are stored in
  the liver and fat and released over time (fat-soluble). They are absorbed by the
  liver, with help from bile. If a blood test shows that these vitamin levels are
  low, this could mean the liver is not absorbing them properly.

• Zinc. This is a nutrient that is absorbed by the liver.
  If a blood test shows a low zinc level, this could mean the liver isn’t absorbing
  zinc properly. This can worsen conditions brought on by high levels of
  ammonia.

Several other lab tests may be done
to check for specific liver problems once liver damage is found. These include:

• Autoimmune antibodies

• Ceruloplasmin (Wilson
  disease)

• An iron panel
  (hemochromatosis)

• Alpha-1 antitrypsin
  (alpha-1-antitrypsin deficiency)

Other tests to check the liver

The tests below may be done to
check the liver’s condition or function. These tests can also check related organs,
such as the gallbladder or bile ducts.

• Liver biopsy. This is a test to look for damage in
  liver tissue. A needle is used to take a small amount of tissue from the liver.
  The tissue is sent to a lab, where it is checked for signs of inflammation,
  scarring, or other problems.

• CT scan. A CT scan is a series of X-rays that make a
  3-D picture of the liver and gallbladder. This can show gallstones, abscesses,
  abnormal blood vessels, or tumors.

• ERCP (endoscopic retrograde cholangiopancreatography).

  This test can show if the bile ducts are blocked or narrowed. It can also
  take pictures of the gallbladder. During this test, a small flexible tube
  (endoscope) is put into the mouth. The tube is moved down the esophagus and
  stomach to the top of the small intestine. This is where the bile ducts are. Dye
  is released through the tube to make the bile ducts show up on an X-ray. The
  healthcare provider may also use small tools to take tiny samples of tissue or
  fluid. These are sent to a lab to be studied.

• HIDA scan. This test checks gallbladder and liver
  function. A small amount of radioactive fluid is put into the body. This fluid
  will be seen on a scan as it travels through the liver to the gallbladder and into
  the intestine. It can show if bile ducts are missing or blocked. It can show if
  the gallbladder is working properly. It can also show other problems in the bile
  ducts.

• MRI. This test uses magnets, radio waves, and a
  computer to create an image of the organs and tissues in your body.

• MRCP (magnetic resonance cholangiopancreatography).
  This is a type of MRI that is more detailed than a standard MRI. It can show
  abnormal or narrow bile ducts, tumors, gallstones, or all three.

• Ultrasound (sonogram). This test uses harmless sound
  waves and a computer to create a picture of the liver, gallbladder, and bile
  ducts. It can show gallstones, tumors, or fat in the liver. It is also used to
  check the condition of the blood vessels and look for bile collections where bile
  may leak out of the liver. A special ultrasound called elastography gives more
  information about scarring in the liver (cirrhosis).

First symptoms and signs of liver disease in men

Contents

• 1 Signs and first symptoms of liver disease in men: pay attention urgently
  • 1. 1 What is the liver and how does it function
  • 1.2 Liver diseases: main forms and symptoms
    9000 5 1.2.1 Cirrhosis of the liver
    • 1.2.2 Hepatitis
    • 1.2.3 Fatty liver disease
    • 1.2.4 Liver failure
  • 1.3 Why are men more likely to suffer from liver disease?
  • 1.4 What are the symptoms of liver disease
  • 1.5 Why is early detection and treatment of liver disease important in men?
  • 1.6 Necessary tests for suspected liver disease
    • 1.6.1 Which tests are needed first:
  • 1.7 Methods for diagnosing liver disease in men
    • 1.7.1 Clinical signs
    • 1.7.2 Blood tests
    • 1.7 .3 Ultrasound diagnostics
    • 1.7.4 Liver biopsy
  • 1.8 What treatment methods are used for liver diseases?
    • 1.8.1 Drug treatment
    • 1.8.2 Diet
    • 1.8.3 Surgery
    • 1.8.4 Alternative medicine
  • men
    • 1.9. 1 Nutrition
    • 1.9.2 Physical activity
    • 1.9.3 Check-ups
  • 1.10 How to keep your liver healthy
    • 1.10.1 Dietary changes:
    • 1.10.2 Healthy lifestyle:
  • 1.11 Video on the topic:
  • 1.12 Question-answer:
    • • 1.12.0.1 What are the symptoms of liver disease in men?
      • 1.12.0.2 What factors can contribute to liver disease in men?
      • 1.12.0.3 What diagnostic methods are used to detect liver disease in men?
      • 1.12.0.4 Which liver diseases are most common among men?
      • 1.12.0.5 How can liver disease be prevented in men?
      • 1.12.0.6 How is liver disease treated in men?

Learn about the first symptoms and signs of liver disease in men: fatigue, pain in the right side, nausea, jaundice and other symptoms. It is important to see a doctor on time and undergo regular examinations to prevent serious consequences and maintain liver health.

The liver is an important organ in the human body that performs a number of functions, such as removing toxins from the blood, producing bile, and processing nutrients. However, if its functions are violated, men may experience various diseases that need to be detected in a timely manner.

Liver disease in men can manifest itself in very different ways, but there are a number of signs that should be considered in order to identify health problems in a timely manner and prescribe appropriate treatment. In this article, we will look at the first symptoms of liver disease in men and what should be done if they appear.

Knowing the signs of liver disease is important to prevent serious complications and keep a person healthy. But do not forget that early detection and treatment of liver disease can prevent its development and maintain health for many years.

What is the liver and how does it function

The liver is the largest internal human organ, located in the right upper quadrant of the abdomen. The main function of the liver is to filter the blood and remove harmful substances that enter the body through food, drink or air. In addition, the liver performs a number of other functions that support the normal functioning of the body.

The processes that take place in the liver can be divided into several categories. One of the most important functions of the liver is metabolism. The liver breaks down food from the stomach and intestines into nutrients and other substances that can be used in the body. In addition, the liver is involved in the metabolism of drugs and other chemicals. Another important function of the liver is the production of bile, which allows the digestion of fatty foods.

If liver function is impaired, it can lead to various diseases, including metabolic disorders, bile insufficiency and other problems. Therefore, it is important to take care of the health of the liver and monitor its condition.

Liver diseases: main forms and symptoms

Liver cirrhosis

Liver cirrhosis is one of the most severe liver diseases, which is characterized by a change in the structure of the organ. The main signs of liver cirrhosis are jaundice, swelling, increased urine output, and the formation of spider veins on the skin.

Hepatitis

Hepatitis is an inflammatory disease of the liver that can lead to malaise, fever and jaundice. Depending on the cause of hepatitis, there are several types: A, B, C, D and E.

Fatty liver disease

Fatty liver disease is a metabolic disorder in which fat begins to accumulate in the liver cells. The main symptoms are an increase in the size of the liver, heaviness and discomfort in the right hypochondrium, increased fatigue and drowsiness.

Liver failure

Liver failure is a condition in which the liver cannot perform its functions. Among the main symptoms of liver failure are nausea, vomiting, abdominal enlargement, itchy skin and general weakness.

• The liver is an important organ that performs many functions in the human body;
• Most of the liver diseases develop unalloyed and manifest themselves for a long time dimly;
• The main causes of liver diseases are malnutrition, alcoholism, medication;
• Due to the fact that liver diseases can be hidden, it is important to have regular medical examinations and check the condition of this organ.

Why are men more likely to suffer from liver disease?

Liver disease is on the rise all over the world and it is a problem not only for women but also for men. However, statistics show that men are at risk of liver disease more than women.

Also, men are less concerned about their health and do not go to the doctor in the early stages of liver disease, which leads to the progression of the disease and the development of complications.

• It is important to note that some liver diseases can be hereditary, so men who have a parent with liver disease are at higher risk of the disease.
• Another reason for the high risk of liver disease in men is professional activity associated with exposure to toxic substances on the liver. This may be due to work in the chemical industry, the production of non-ferrous metals or agriculture.

Therefore, men should pay special attention to their health, and mature men should have regular liver examinations. Leading a healthy lifestyle can significantly reduce the risk of liver disease.

What are the symptoms of liver disease

In the early stages of liver disease, men may not show any symptoms, but as the disease progresses, the body begins to give signals. In particular, one of the first signs may be fatigue, which does not go away even after normal rest or sleep. This is due to the fact that the liver cannot cope with its functions normally and partially “lags behind” other organs, which affects the overall performance of a person.

• Headache and fatigue
• Indigestion and metabolism
• Pain in the abdominal cavity

Other symptoms of liver disease in men can be pain in the right side or in the liver area, as well as the appearance of gallstones. In addition, liver disorders can lead to jaundice and itching of the skin.

It is important to note that the symptoms of liver disease can also occur with other diseases, so for an accurate diagnosis, you need to see a doctor and conduct the necessary studies.

Why is early detection and treatment of liver disease in men important?

The liver is one of the most important organs in a man’s body, performing many functions: blood purification, protein synthesis, glycogen storage, etc. However, liver problems can lead to serious consequences, even death.

Consideration by a specialist of indicators of a biochemical blood test will allow timely detection of certain liver pathologies, such as cirrhosis or hepatitis. By not contacting a medical institution, you can miss the onset of the development of the disease and bring your health to an extreme degree of danger.

Modern medicine has the ability to carry out a very effective treatment of liver diseases, especially in the initial stage. In addition, a disease detected in time has a higher chance of a full recovery of the body.

Timely visit to a doctor and diagnosis of liver diseases is a step towards a healthy lifestyle and longevity.

Necessary tests for suspected liver disease

When the first signs of liver disease in men, such as fatigue, jaundice, pain in the right hypochondrium, it is necessary to consult a doctor and undergo the necessary tests. The doctor, paying attention to the test results, will be able to make an accurate diagnosis and prescribe the appropriate treatment.

What tests should be done first:

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) blood tests – These enzyme levels may indicate damage to liver cells.
• Complete Blood Count – This test shows your general health and can help your doctor detect inflammation.
• Blood for the presence of viral markers of hepatitis B and C – these viruses can lead to cirrhosis of the liver if they stay in the body for a long time.

In addition to these tests, your doctor may order other tests, such as a biochemical blood test, tumor markers, and liver ultrasound. It is important not to delay visiting a doctor in order to detect liver disease in a timely manner and prevent the development of complications.

Methods of diagnosing liver disease in men

Clinical features

Some liver diseases may initially present with persistent fatigue, general weakness, unexplained weight loss, anorexia, nausea, or right upper quadrant tenderness. If they occur, you should seek advice from a gastroenterologist or hepatologist.

Blood tests

Certain changes in blood tests may indicate liver problems. A blood test may show abnormally high levels of aminotransferases (ALT, AST), alkaline phosphatase, or bilirubin, which may indicate damage to the liver cells and difficulty in performing its functions.

Ultrasound

Ultrasound can help the doctor see the size, shape, and structure of the liver. It may also show the presence of fatty infiltration, tumors, enlarged lymph nodes, or portal hypertension. This method is very safe, does not require special training and is economically available.

Liver biopsy

Liver biopsy may be required if the situation is not clear or if other tests are difficult to pass. This process consists of taking a small sample of liver tissue and testing it in the laboratory. It can help diagnose liver disease, evaluate tissue damage, respond to therapy, and help plan the right treatment.

What treatment methods are used for liver diseases?

Drug treatment

Drug treatment is the main treatment for liver diseases. The doctor prescribes an individual course of treatment, which can be taken in the form of tablets or injections. The main groups of drugs include:

• Hepatoprotectors – restore liver cells and protect them from damage;
• Cholagogue – improve the secretion of bile and remove it from the body;
• Antiviral – used for viral liver disease;
• Anti-cancer – used for liver cancer;
• Antibiotics – fight infections that cause liver disease.

Diet

Proper nutrition is an integral part of the treatment of liver diseases. The doctor recommends limiting the consumption of animal fats, canned food, sweets, starchy foods and fried foods. The diet should contain fruits, vegetables, herbs, dairy products, as well as white meat broth, lean meat and fish.

Surgery

Surgery is used for severe cases of liver disease that require tumor removal or organ transplantation. These operations are carried out only in specialized medical centers with strict medical indications.

Alternative Medicine

Alternative therapies may be used in conjunction with primary care, but cannot replace it. Such methods include herbal medicine, acupuncture, homeopathy, yoga and meditation. Before using any of these methods, you should consult your doctor.

Prevention of liver diseases in men

Liver diseases are a serious problem for men, as they are often provoked by an unhealthy lifestyle. However, a number of preventive measures can be taken to prevent the development of liver disease.

Nutrition

The main effect on the liver is food, so it is important to monitor the diet and eat foods rich in vitamins and microelements. Avoid fatty, fried, spicy and smoked foods, alcohol, fast food and sugary carbonated drinks. Include more vegetables, fruits, herbs, fish, dairy products, water, and green tea in your diet.

Physical activity

Regular exercise will not only help you avoid being overweight, which contributes to liver disease, but will also improve blood circulation and metabolism in the body. It is not necessary to play professional sports, it is enough to do morning exercises, run or basketball with friends.

Preventive check-ups

Try to have general check-ups with a doctor every year and do the necessary tests in order to detect possible liver diseases in time and start their treatment.

• Conclusion: Remember that liver disease can be prevented by maintaining a healthy lifestyle, exercising, visiting doctors for preventive check-ups, and eating right. Heed the advice and keep your liver healthy for years to come!

How to keep your liver healthy

Diet changes:

Eating a lot of fatty and fried foods negatively affects liver health. To reduce the load on the body, you need to give up fatty foods and increase the amount of vegetables and fruits in the diet. It is also worth giving up alcohol and sweets.

• Drink more water . It helps to clear toxins from the liver and reduce the burden on the body, so a minimum of 8 glasses of water should be consumed daily.
• Reduce the amount of salt . Excess salt can cause swelling and damage the liver, so you should reduce your dietary intake.

Healthy lifestyle:

In addition to dietary changes, some lifestyle changes can be made.

1. Exercise – This will help you lose weight, reduce liver stress and improve overall well-being.
2. Get enough rest – give the body time to rest and recover.
3. Watch your weight – being overweight can impair liver function, so you should watch your weight and control it constantly.

Following these guidelines will help keep your liver healthy and reduce your risk of developing various diseases.

Related videos:

Q&A:

What are the symptoms of liver disease in men?

Liver disease in men can cause various symptoms such as pain or discomfort in the right upper quadrant of the abdomen, fatigue, loss of appetite, nausea, jaundice, itching, swelling and others. However, not all symptoms are specific to liver disease and may also indicate other health problems.

What factors can contribute to liver disease in men?

Factors that can contribute to liver disease in men include alcohol and drug abuse, viral infections such as hepatitis B and C, obesity, diabetes, and certain drugs and toxins.

What diagnostic methods are used to detect liver diseases in men?

Various methods can be used to diagnose liver disease in men, such as blood tests to detect liver enzyme levels, ultrasound, computed tomography, magnetic resonance imaging, and laparoscopy. Sometimes a liver biopsy may be needed to confirm the diagnosis.

Which liver disease is most common among men?

Among the liver diseases that are most common among men, it should be noted cirrhosis of the liver, viral hepatitis (especially hepatitis C), fatty liver, alcoholic liver disease, liver cancer and others.

How can liver disease be prevented in men?

To prevent liver disease in men, it is recommended to maintain a healthy lifestyle, avoid alcohol and drugs, maintain good hygiene, get vaccinated against viral infections, control weight and diabetes, limit the use of drugs and toxins, and regularly check with a doctor.

How is liver disease treated in men?

Treatment of liver disease in men depends on the type and extent of the disease and may include medication, lifestyle changes, diet, surgery, and liver transplantation. It is important to consult a doctor to prescribe the correct treatment in each case.

Drug-induced liver injury

00:00

Oksana Mikhailovna Drapkina , 0352

– Professor Shirokova Elena Nikolaevna. “Medicated Liver Injuries”.

Elena Nikolaevna Shirokova , Doctor of Medical Sciences, Professor:

– Drug-induced liver damage is a variety of clinical and morphological variants of liver damage that develop in response to medication.

This topic is becoming more and more relevant due to the fact that a huge number of new drugs appear on the market, effective, needed by our patients. At the same time, we are increasingly experiencing reactions to these drugs.

The difficulty in diagnosing drug-induced liver lesions lies in the fact that they often occur under the guise of various hepatopathy. They do not have a characteristic clinical picture.

Drug-induced liver injury occurs with a frequency of one case per 1000 patients to one case per 100,000 patients who take drugs at therapeutic doses. Currently, more than 1000 drugs have been registered that have the ability to cause liver damage.

Drug-induced liver injury does not have a characteristic clinical picture. It can be a completely asymptomatic lesion, or a vivid clinical manifestation up to the development of liver failure. As a rule, patients may complain of itching, lack of appetite, watery eyes, nausea, and in some cases diarrhea.

The following indicators come to our aid from laboratory data. It is gamma-glutamyl transpeptidase. Its increase indicates that the biotransformation system was involved, activated, as a rule, within a few weeks before this indicator increased. Naturally, other reasons for the increase in gamma-HT should be excluded.

It should be noted that this indicator remains normal against the background of taking “Glotala”. In some cases, contraceptives. Alanine transaminase is elevated, usually in association with aspartic transaminase, and indicates an inflammatory liver lesion. The de Ritis coefficient (the ratio of the level of aspartic transaminase to the level of alanine transaminase), as a rule, is less than one (inflammatory type of response).

Decreased cholinesterase indicates that the patient has decreased synthetic liver function as a result of toxicity. An increase in the level of alkaline phosphatase indicates the development of cholestasis.

It is believed that the determination of the first three parameters of the level of gamma-HT, alanine transaminase, cholinesterase is a fairly rational test with 95% sensitivity in the diagnosis of drug-induced liver damage. Research also the level of the fourth parameter (alkaline phosphatase) increases the sensitivity to 96%.

03:00

Currently, it is customary to operate with a classification of drug-induced liver lesions, which is based on an increase in the level of basic biochemical samples. Allocate hepatocellular, cholestatic and mixed drug-induced liver injury.

If the level of alanine transaminase is increased by more than 5 times the upper limit of normal, and the index R, which is defined as the ratio of the level of alanine transaminase to the level of alkaline phosphatase, is greater than or equal to 5, it is customary to talk about hepatocellular liver damage.

If the level of alkaline phosphatase is increased by more than 2 times, and the R index is less than or equal to 2, we are talking about cholestatic liver damage.

If both alanine transaminase and alkaline phosphatase increase more than 2 times from the upper limit of the norm, and the R index is in the range from 2 to 5, then we are talking about mixed liver damage.

It should be said that cholestatic liver lesions take longer, that is, they resolve more slowly than hepatocellular ones. At the same time, the severity of hepatocellular damage is higher than that of cholestatic ones.

Registry data from American and Spanish authors who analyzed patients with drug-induced liver injury. In both cases (in the American registry, the medical records of 300 patients were analyzed, in the Spanish registry – more than 600 patients), hepatocellular lesions dominate.

In the US study, their share is 57%, while in the Spanish study it is 55%. Cholestatic lesions are presented more modestly. This is 23% in the American study and 25% in the Spanish one. Mixed lesions – 20% and 21%, respectively.

05:02

Interestingly, the age of the patient influences the phenotype of drug-induced liver injury. According to Spanish authors published in the journal Hepatology in 2005, it was shown that cholestatic lesions are more likely to develop in men over 60 years of age. At the same time, hepatocellular lesions often develop in women under 60 years of age.

The severity and outcome of drug-induced liver injury is largely determined by the type of injury. The cumulative survival rate in cholestatic and mixed drug-induced liver lesions is significantly and significantly higher than the survival rate of patients suffering from hepatocellular liver lesions.

Mortality in the study of Spanish authors in hepatocellular liver damage was 7%. While with cholestatic – 5%, with mixed lesions – 2%.

A similar distribution was obtained according to Swedish authors: 12.7% for hepatocellular lesions, and 7.8% for cholestatic lesions.

A Spanish study identified predictors for the development of fulminant liver failure in the development of drug-induced injury. They turned out to be: a high level of bilirubin, the presence of hepatocellular lesions and female sex.

Different ratio. These are data from the American Register of Study of Drug-Related Liver Injuries. Here, lethality mainly prevailed among cholestatic lesions – 14.3 versus 7.5 in hepatocellular lesions.

But in fairness it must be said that this group of patients with cholestatic liver damage had lethal outcomes that were not associated with the development of liver failure, but with a number of other reasons. Although with the development of liver failure (naturally, an excess of bilirubin), the risk of developing both renal failure and the addition of infectious complications increases. It also worsens the patient’s prognosis.

According to Swedish authors, an independent predictor of poor prognosis in both hepatocellular and cholestatic drug-induced liver injury determined the level of bilirubin in the blood serum.

07:46

Until now, there is no clear answer to the question of which drug-induced liver injury should be considered chronic. It has been shown that already 3 months after the onset of drug-induced liver damage, fibrosis can develop. So it is logical to consider 3 months as the time interval after which we can talk about the development of chronic drug-induced liver damage.

At the same time, it has been shown that cholestatic lesions proceed much more slowly and resolve more slowly. Here the terms are longer – 6 months or more. Currently, it is considered that persistent liver disease (in the case of hepatocellular) should be considered: if the increase in the level of liver tests exceeds the interval of 3 months. 6 months – persistence for cholestatic lesions.

Chronic drug-induced liver injury should be considered when changes in liver function tests have been recorded for more than 12 months.

Data from a Spanish study with long-term follow-up of patients with drug-induced liver injury. A total of 258 patients took part in the study. A cure was observed in half of the patients (53%), a chronic course of drug-induced liver injury took place in 47%. Of these, resolution within a period of up to a year was observed in 35% of patients. Persistence for more than a year – in a larger number (65%). Long-term resolution of them was observed in 48%, and long-term persistence – in more than half of the patients (52%).

Interesting results: of these 52% (out of 38 people), 10 were diagnosed with autoimmune hepatitis. Apparently, the drug lesion, taking the drug acted as a trigger factor for the manifestation of autoimmune hepatitis. Among the remaining 28, 10 were diagnosed with hepatocellular lesions, 18 with cholestatic or mixed lesions.

10:12

There are two types of drug reactions in response to taking a drug. Type A – these are dose-dependent, predictable reactions, characterized by a direct damaging effect. As an example, exposure to alcohol substitutes or paracetamol (in fact, the only drug for which a toxic dose-dependent effect has been described).

The second type of reaction B is dose-independent reactions, unpredictable. As a rule, we encounter in our histological practice type B reactions, hypersensitivity reactions. They, in turn, are divided into allergic reactions, pseudo-allergic reactions and reactions that proceed according to the type of idiosyncrasy. The last two most common reactions in the practice of the therapist.

As for the morphological equivalent of drug-induced liver injury, as a result of direct hepatotoxicity, we can observe the development of necrosis, steatosis and cholestasis. In some cases, we are faced with the development of a tumor process. With idiosyncratic reactions, we are faced with the development of cholestasis and necrosis, or necrosis and steatosis.

In practice, it is often difficult to isolate any one type of liver damage. As a rule, we are faced with a combined lesion.

As an illustration, I give a histological preparation of the development of cholestatic hepatitis. Degenerative changes in the epithelium of the bile ducts are presented. But if we appeal to the opinion of only a morphologist, then, of course, we will not get an answer to the question: what was the trigger factor for the development of these liver changes.

What happens when a drug enters the hepatocyte? By diffusion of sinusoids through the membrane, the drug enters the liver. It is transported by proteins to the endoplasmic reticulum, where biotransformation processes take place.

They are usually divided into two phases. The first phase is the hydroxylation oxidation reaction. As a result, intermediate metabolites are formed. Some of them may be toxic.

Second phase reactions are reactions associated with glucuronic acid, sulfate, glutathione. Sulfation reactions, glucuronidation, that is, the transfer of drugs into non-toxic substances, into substances that are already easily excreted into the blood or bile. Moreover, the activity of transporters on the biliary polis of the hepatocyte depends on the degree of saturation with the transported substance and occurs with the participation of ATP.

13:02

(Slide show).

This diagram illustrates a number of hepatocyte apical membrane transporters that mediate the excretion of various substances from the hepatocyte into the bile ducts. Top left is the bile acid export pump (called BSEP), which is encoded by the ABCB11 gene. It is responsible for the transport of bile acids.

If the function of this carrier is disturbed, then there is an accumulation of bile acids, cholestasis, damage to the hepatocyte. The multidrug resistance transporter MRP2 is mainly responsible for the transport of conjugated conjugated bilirubin. It also transports a number of organic anions and hepatocytes in the bile duct.

MDR3 vector – multidrug resistance vector. Act as an intermediate phase for phosphatidylcholine. Carries phosphatidylcholine, which forms mixed micelles of cholesterol bile.

Drugs, predominantly cations, are carried by a multidrug resistance vector called MDR1. If there is some kind of genetic predisposition, which is represented by nonsense or missense mutations, then under the influence of xenobiotics, violations of the work of these transporters are detected. This, accordingly, leads to the accumulation of toxic components in the hepatocyte and to the death of the hepatocyte.

In case of accumulation of toxic components, drug metabolites, bile acids in the hepatocyte, alternative excretion routes are switched on. On the basolateral membrane there are representatives of multidrug resistance proteins. In particular, these are MRP3, MRP4.

Under normal conditions, when the liver functions normally and nothing threatens it, they are actually not active. But if the work of other carriers of the apical membrane is disturbed, then they take on new functions. They begin to work with triple strength.

15:08

As for the direct toxicity effects of various drug metabolites that occur in the liver, hepatocyte. They carry out their action. They can damage DNA. They can damage lipids and proteins. They can activate the process of lipid peroxidation, deplete ATP reserves, promote the formation of free radicals, disrupt the normal cytoskeleton, and so on.

How do these reactions of direct toxicity of reactive metabolites occur? There is a destruction of cross-links between the protein, there is a splitting of microfilaments, which disrupts the transport of cell division. DNA fragmentation triggers the Caspase cascade, which leads to apoptosis, to programmed cell death.

In addition to the actions of toxic metabolites presented, other mechanisms of drug-induced liver injury have been described. In particular, due to a violation of calcium homeostasis, there is a violation of the assembly of fibrylactin on the surface of the hepatocyte membrane. Air bubbles form. Air bubbles in the cell membrane lead to disruption of its integrity, which leads to cell lysis.

The letter B denotes the processes that occur on the apical polis of the hepatocyte. Transport membranes, multidrug resistance proteins can be damaged. This contributes to the accumulation of toxic elements, bile acids in the hepatocyte and also leads to liver damage.

Cytochrome P450-formed toxic metabolites are transported by endoplasmic reticulum transporters to the hepatocyte surface. They can act as antigenic targets for various cytokines.

Interaction with tumor necrosis factor receptors IFAZ leads to the launch of the Caspase cascade and to programmed cell death (apoptosis). A number of drugs can affect the function of mitochondria – inhibit beta-oxidation. Violation of the metabolism of free fatty acids leads to the accumulation of lactate and free radicals. This disrupts the function of mitochondria.

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Mechanisms that influence the development of oxidative stress. On the one hand, this is a pharmacological effect. These are reactive oxygen species that are produced by reactive metabolites of drugs. On the other hand, a reactive form of oxygen that can be produced by bile acids.

In addition, genetic characteristics also matter. Mitochondria contain an enzyme called superoxide dismutase. This is the main scavenger of superoxide, the main protector of the cell from destruction. There is also peroxidase, which promotes the conversion of hydrogen peroxide, reduction with the formation of water. It is the second main protector of the cell’s mitochondria.

If there are some genetic features that lead to disruption of the work of these enzymes, then in combination with pharmacological influences and the influence of external factors, this leads to cell damage.

What to do in case of drug-induced liver injury? Of course, immediate withdrawal of the drug is necessary. In the presence of a hypersensitivity reaction, glucocorticosteroids are indicated. If cholestasis develops, then Ursodeoxycholic acid is the undisputed leader here.

Based on what we have now learned about the possible mechanisms for the development of drug-induced liver damage, the use of drugs that have, respectively, an antioxidant, metabolic effect, including essential phospholipids, is pathogenetically justified.

I would like to dwell on this part in more detail. It is known that hepatocytes, other cells and various organelles have membranes that mainly consist of lipids (by 52–54%). 42 – 46% are proteins. Carbohydrates act as antennas for tissue-specific receptors.

The surface area of ​​the hepatocyte membrane and organelles is 33,000 square kilometers. This is 5 times the area of ​​a football field. Moreover, the share of the basalothermal membrane accounts for 85%. The rest is the apical membrane.

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The main component of the membrane are phospholipids. 65% are accounted for by them. Phospholipids have a different structure. Basically, these are phosphate esters of glycerol. Depending on the composition, choline-containing phospholipids are located on the outer layer of the membrane. The inner layer is amine-containing phospholipids.

This ratio ensures the flexibility of the membrane, its fluidity, which allows the membrane to exercise its properties. Phospholipids form the backbone of the membrane, which is necessary for normal functioning. Phospholipids are known to form a double layer in an aqueous medium. Moreover, the hydrophilic parts of the molecule are located on the outer and inner sides of the membrane. Inside are hydrophobic parts.

This ensures continuity and fluidity of the membrane. Provides both lateral movement of phospholipids and proteins, and movement by the “flip-flop” mechanism between the outer and inner layers of the membrane.

How do essential phospholipids work? Why are these drugs attractive for the treatment of drug-induced liver injury?

Essential phospholipids are known to have membrane-protective properties. They normalize the fluidity of cell membranes. They contribute to the repair of hepatocytes, restoring damaged structures so that the diseased liver does not expend its energy (this is an energy-intensive process) on restoring damaged cell membranes.

In addition, essential phospholipids normalize redox processes, that is, they have an antioxidant effect. Protect cells from oxidative stress. This is actually the cornerstone of the development of drug-induced liver injury – damage to hepatocytes.

Importantly, essential phospholipids have an antifibrotic effect by acting on stellate cells and procollagen production.

22:31

Respiratory mitochondrial enzymes that are designed to protect the cell from damage. Their activity, their activity is directly related to the level of phospholipids. The level of enzyme activity is also directly dependent on the content of polyunsaturated fatty acids in phospholipid molecules.

It is important that the intake of essential phospholipids allows you to quickly cope with pathological changes in biochemical parameters. In addition, these drugs may be given prophylactically along with drugs that often cause drug-induced liver injury.

As you well know, in some cases we cannot refuse to prescribe anti-tuberculosis, anti-tumor therapy. Here we need helpers – drugs that could neutralize the toxic effects of these drugs. Essential phospholipids work well in this situation as well.

In conclusion, I would like to emphasize once again that a systematic approach is needed to determine the causes of hepatotoxicity. A thorough analysis of clinical and anamnestic laboratory and instrumental data is necessary in order to judge what caused liver damage.

A number of universal molecular mechanisms for the development of drug-induced liver injury have now been identified. In practice, it is advisable for a doctor to use the biochemical classification of drug-induced liver lesions.

Drug-induced cholestasis is milder but resolves much more slowly than hepatocellular liver disease.

As a therapeutic tactic (of course, if possible), stop the drug that caused the drug-induced liver injury.