home Analyzes Pathogenesis of alcoholic and non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease: why it occurs and how to treat it. Who is at risk

Pathogenesis of alcoholic and non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease: why it occurs and how to treat it. Who is at risk

What is it and is it possible to get rid of it? It all depends on the patient and his willpower. It’s not so easy to change your lifestyle and improve your diet. But these simple changes will bring the body back to normal and prevent the occurrence of liver disease.

If liver dysfunction is detected, the cause of the disease should be established, and treatment should begin based on it. Timely diagnosis will not hurt. The risk category includes women, as well as men who drink alcohol.

What is steatosis?

Fatty liver degeneration, or as it is also called steatosis, is a pathology. With this disease, fat, in the form of droplets, collects in hepatocytes. When a large amount of fat accumulates, the hepatocyte bursts and the fat gets into the space between the cells, thereby creating a cyst, which prevents the liver from functioning normally.

This disease occurs at any age, even in children. But it most often occurs after the age of forty-five. Individuals of the weaker sex are more susceptible to non-alcoholic steatosis. Representatives of the stronger sex – steatosis, which appeared as a consequence of regular intake of alcoholic beverages. Steatosis can be either an independent disease or a consequence of another disease (diabetes mellitus, etc.).

Diagnostics

To obtain reliable results, comprehensive diagnostics should be carried out. First of all, the following studies should be carried out to help avoid steapathogenesis:

Tests for the presence of steatosis, which help assess the condition of the liver and reliably establish a diagnosis. It is advised to take a biochemical blood test, which will assess the rate of iron metabolism. In combination with it, a genetic test is carried out in order to exclude hemochromatosis. They also donate blood for serology, which helps determine the presence of any form of viral hepatitis. In people with steatosis, normal levels of bilirubin, albumin and prothrombin are observed. But serum tragsaminase and alkaline phosphatases increase slightly. If the causative agent of the disease is alcohol, then the amount of enzyme g-glutamyl transpeptidase increases.
Ultrasound diagnostics is a necessary study for such a disease. It can be analyzed either independently or in combination with others. Determines the size of the liver and the occurrence of tumors. It is advised to conduct an ultrasound of the spleen, because with second and third degree disease, it increases in size.
A biopsy is a puncture in which the material taken is examined under a microscope and the presence of fat is determined.
Tomography helps to establish tissue density and determine all changes that have occurred in the liver.

First degree liver steatosis is the accumulation of fat in cells, which does not lead to destruction of their structure.

Second-degree steatosis is the occurrence of fatty tumors between tissue cells, which leads to serious consequences.

Moderate steatosis is the appearance of cysts based on neutral fats that do not destroy the cell structure.

Causes and symptoms of the disease

The main cause of steatosis is said to be metabolic disorders and imperfect hormonal levels. As a result, diabetes mellitus manifests itself and the amount of lipids in the blood increases. And this leads to heart problems.

Also, the causes of pathology can be:

Bad habits;
Overeating and excess weight;
Hepatitis viruses;
Poor nutrition;
Metabolic syndrome;
An increase in the amount of liver enzymes;
Genetics;
Use of non-steroidal anti-inflammatory drugs.

In some cases, symptoms of steatosis do not show themselves. Then it can only be detected during specialized diagnostics. The most common symptoms of the disease are weakness of the body, nausea, a sharp increase in the size of the liver, and pain under the right hypochondrium.
Very often, patients are exposed to various types of infections. This is due to low immunity.

Types of steatosis

Liver steatosis can manifest itself in the following forms:

Diffuse steatosis

It occurs when fatty deposits do not appear in the second and third lobes of the liver, but are distributed diffusely (over the entire surface of the organ).

Fatty steatosis

It affects not only the increase in liver size, but also its color. With this type of disease, it changes to yellowish or red-brown. The result is the death of liver cells. It is asymptomatic; fatty stetosis can be determined only after undergoing an ultrasound examination.

Alcoholic steatosis

Caused by alcohol intoxication. The second name is fatty liver degeneration. There are many reasons why the disease manifests itself in this form. The most important thing is the consumption of drinks containing alcohol. The progress of the disease is directly related to the dose of alcohol: the higher it is, the faster pathological processes occur.

The consequences are completely reversible and treatable. But if the recommendations are not followed, alcoholic steatosis becomes a serious disease. It occurs in two forms: macro- and microvesicular. The first is a chronic manifestation of the disease, the second is an acute form.

Non-alcoholic steatosis

They are called differently: infiltration, fatty degeneration or non-alcoholic fatty disease. If timely treatment is not carried out, this type of steatosis can develop into steatohepatitis, fibriosis or cirrhosis. Occurs due to excess weight, diabetes or anastomosis. Also, it can accompany people who are suddenly losing weight or are receiving parenteral nutrition.

Non-alcoholic steatosis can also occur as a result of a large number of bacteria in the intestines or taking certain medications. It is difficult to determine the disease using diagnostics. All indicators are normal, only slightly increased activity of serum transaminases. A reliable diagnosis can only be made after magnetic resonance imaging.

Focal steatosis

With it, the disease can be determined only in the case of a slight increase in the activity of the enzymes of cholestasis and cytolysis. Diagnosis can only be made through instrumental studies. If the tumor is benign, then it will have smooth and clear contours of different sizes.

Which doctor should I contact?

If pain occurs in the liver area, it is advised to first consult a therapist. After carrying out the necessary diagnostics, he will refer you to a more specialized specialist. If steatosis is in the initial stage, then the general practitioner is quite capable of prescribing treatment himself.

If the patient is quite sure that pain in the right hypochondrium is a problem with the liver, then you can safely go to a gastroenterologist. It treats not only pathologies of the gastrointestinal tract, but also the liver.

If it is impossible to establish a reliable diagnosis, you should contact a specialist such as a hepatologist. He has more in-depth knowledge of various treatment methods, which helps to reliably establish a diagnosis and choose a course of treatment. The downside is that not all clinics have such a doctor.

Drug treatment

The course of treatment for steatosis is selected individually for each patient, based on the causes and types of the disease. The cause can be determined by diagnosing the level of cholesterol, ceruloplasmin and the amount of enzymes. The following groups of drugs are prescribed:

Lipotropic, which affects metabolism. This includes folic acid, lipoic acid, and all B vitamins.
Hepatoprotectors that protect hepatocytes from damage. These are the drugs Hepa-Merz, Ursohol, Essentiale, Heptral, Karsil.
Statins and fibrates, which normalize lipid volume and prevent fat from accumulating on the walls of blood vessels.
Thiazolindiones, which regulate the amount of sugar in the blood. This group includes Prioglitazoline, Rosiglitazoline.

A remedy such as Metformin helps with fatty steatosis. The principle of its action is to prevent the production of glucose by cells. Based on this, sugar and fat metabolism is regulated.

It is very important to take products based on milk thistle: Karsil, Legalon, Gepabene and Silymarin. They relieve symptoms and lead to faster healing.

Treatment with folk remedies

There are many herbs that cleanse and restore the liver. The main ones are milk thistle and calendula. They are used in the form of oils, decoctions and infusions. Also, effective plants are:

If you have liver steatosis, it is advisable to eat several apricot kernels per day, since they contain a high level of vitamin B5.

To prepare a decoction of milk thistle, you need to take it and dandelion root in the same proportion (one spoon each). Steam half a liter of water in a thermos. Leave for twenty minutes. Take a glass twice a day.

This recipe will also help: cut off the top of the pumpkin and clear it of seeds. Pour honey inside. Infuse for fourteen days. Afterwards, drain the honey and take a spoonful of it three times a day.

Take the cocktail on an empty stomach. For it, you should mix milk and carrot juice (one hundred milliliters of each substance).

For steatosis, it is recommended to use a glass of rosehip decoction twenty minutes before meals.

Possible complications

Since the liver is an organ that leaves an imprint on the work of other systems, treatment of steatosis should begin as soon as possible.

First of all, the digestive system suffers, as bile stagnates and stones form. Unpleasant changes occur in the cardiovascular system. Blood pressure increases, shortness of breath and varicose veins occur. Vision and skin elasticity may decrease.

There is a violation of hormonal balance, as well as a decrease in immunity.

Diet

To create a recommended menu, it is advisable to visit a specialist. But first of all, you need to reduce the calorie content of your diet. The diet should be balanced, namely the food ratio is 1:1:4 (proteins, fats, carbohydrates). You need to eat three to four times a day with a five-hour break.

Products to be excluded:

With steatosis, the patient should include in his diet dairy products, stewed and boiled fish, vegetables, fruits and flour (not confectionery).

Prevention

Prevention of steatosis primarily involves revising your lifestyle. Food should be of high quality and healthy. Special attention should be paid to physical activity - walking, sports and gymnastics. Alcohol can be consumed in minimal quantities, or better yet, avoid it altogether.

And finally

For those who are interested in whether steatosis can be cured, there is only one answer - it all depends on the patient and his desire. To avoid problems with the liver, you need to reconsider your lifestyle, adjust your routine, activity and nutrition.

For those who suffer from a more severe stage. It is advised to completely abstain from alcohol and carry out timely diagnostics to determine at what stage the disease is. And don’t forget to visit the doctor periodically.

Be the first to comment!

Currently, non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases in hepatology, leading to a deterioration in the quality of life, disability and death. First of all, this is due to the high risk of progression of NAFLD with the development of non-alcoholic steatohepatitis (NASH), liver failure and hepatocellular carcinoma. The overall prevalence of NAFLD in the population ranges from 10 to 40%, while the incidence of NASH is 2-4%.

Epidemiology and pathogenesis of NAFLD

The concept of NAFLD combines a spectrum of clinical and morphological changes in the liver, represented by steatosis, NASH, fibrosis and cirrhosis, developing in patients who do not drink alcohol in hepatotoxic doses (no more than 40 g of ethanol per day for men and no more than 20 g for women). NAFLD occurs in all age groups, but women aged 40-60 years with signs of metabolic syndrome (MS) are at greatest risk of developing it.

The pathogenesis of NAFLD is closely related to the insulin resistance syndrome (IR), as a result of which triglycerides (TG) accumulate in the liver and fatty liver disease (FHL) is formed - the first stage or “push” of the disease. Subsequently, free fatty acids (FFA) are released from adipose tissue and synthesized de novo in hepatocytes, which contribute to the occurrence of oxidative stress, which is the second “push” of the disease and leads to the development of inflammatory-destructive changes in the liver in the form of steatohepatitis.

The maximum risk of developing NAFLD was observed in the group of people with MS - these are patients with type 2 diabetes mellitus (DM), obesity, and hypertriglyceridemia. The incidence of NAFLD in patients with type 2 diabetes and obesity, according to various studies, varies from 70 to 100%. At the same time, type 2 diabetes or impaired glucose tolerance (IGT) are observed in 10-75%, obesity - in 30-100%, hypertriglyceridemia - in 20-92% of patients with NAFLD. At the same time, signs of NAFLD are found in 10-15% of people without clinical manifestations of MS, which may be due to other pathogenetic mechanisms of NAFLD formation, for example, the syndrome of excessive proliferation of bacteria in the intestine or dysbiosis, as is commonly formulated in the domestic literature.

The main mechanisms for the development of NAFLD in intestinal dysbiosis are associated with impaired synthesis of apo-lipoproteins of classes A and C, which are the transport form for TG in the process of formation of very low-density lipoproteins (VLDL), as well as intestinal endotoxicosis, which allows us to consider this condition as an additional source of oxidative stress (Fig.).

The relationship between the pathogenesis of NAFLD and IR allows us to consider this disease as one of the independent components of MS, the clinical significance of which lies in the significant progression of atherosclerotic vascular damage.

A number of studies have shown that NAFLD increases the risk of cardiovascular diseases (CVD) regardless of other predictors and manifestations of MS. This is confirmed by several facts, which include the association of NAFLD with plasma adiponectin concentration. It is known that adiponectin has an antiatherogenic effect and, according to many prospective studies, a decrease in its level is an early predictor of CVD and MS. Patients with NAFLD had lower plasma adiponectin concentrations than healthy controls.

In addition, in this category of patients, compared with the control group, there is a significant increase in the intimal thickness (TI) of the carotid artery, which is also recognized as a reliable subclinical sign of atherosclerosis. It has been proven that a TI value of less than 0.86 mm is associated with a low risk of CVD, and more than 1.1 - with a high one. In patients with NAFLD, its value averages 1.14 mm.

Another subclinical sign of atherosclerosis found in patients with NAFLD is the identification of endothelial dysfunction, which is confirmed by a decrease in endothelium-dependent vasodilation of the brachial artery in patients with NAFLD. Moreover, a decrease in this indicator correlates with the degree of morphological changes in the liver, regardless of gender, age, IR and other components of MS.

Thus, the pathogenesis of NAFLD is inextricably linked with MS, and the very fact of the development of this pathology changes the prognosis for these patients, both in the form of progression of liver failure and in the form of a significant increase in the incidence of CVD complications.

Clinic and diagnostics

In general, NAFLD is characterized by an asymptomatic course, therefore, most often in practice, a doctor is faced with cytolysis syndrome accidentally discovered during a biochemical study. In this case, a patient with NAFLD, as a rule, either does not present complaints, or they are nonspecific in the form of asthenovegetative syndrome (weakness, fatigue) and discomfort in the right hypochondrium. The presence of skin itching, dyspeptic syndrome, along with the development of jaundice and portal hypertension, indicates an advanced stage of NAFLD.

During an objective examination of patients with NAFLD, attention is drawn to hepatomegaly, which occurs in 50-75%, and splenomegaly, detected in 25% of patients.

Laboratory tests for NAFLD are characterized by the following changes:

An increase in the activity of alanine (ALT) and aspartic (AST) aminotransferases by no more than 4-5 times, the AST/ALT index is no more than 2, more often the ALT activity is increased;

Increased activity of alkaline phosphatase (ALP) and g-glutamyl transpeptidase (GGTP);

Hypertriglyceridemia, hypercholesterolemia;

Hyperglycemia (IGT or type 2 diabetes);

Hypoalbuminemia, increased bilirubin levels, thrombocytopenia, increased prothrombin time in patients with advanced stage NAFLD.

The main differential difference between GC and NASH, available in clinical practice, may be the severity of the biochemical syndrome of cytolysis.

It should be noted, however, that the absence of changes in laboratory parameters characterizing the functional state of the liver (ALT, AST, ALP, GGTP) does not exclude the presence of an inflammatory-destructive process and fibrosis.

As mentioned above, a diagnostic search is carried out in connection with the identification of cytolysis syndrome in a patient, while the presence of type 2 diabetes, abdominal obesity, arterial hypertension and lipid metabolism disorders indicates a high probability of NAFLD. Making this diagnosis is quite difficult due to the need to exclude all other causes causing cytolysis, macrovesicular steatosis and inflammatory-destructive changes in the liver. The secondary nature of liver damage should be excluded (Table 1).

To clarify the diagnosis, instrumental methods can be used (ultrasound (ultrasound), computed tomography (CT), magnetic resonance imaging (MRI)), which make it possible to verify hepatomegaly, indirectly assess the degree of liver steatosis and register the formation of portal hypertension.

Ultrasound is an inexpensive and, according to some authors, a fairly informative instrumental method for diagnosing liver steatosis. There are 4 main ultrasound signs of liver steatosis:

Distal echo attenuation;

Diffuse hyperechogenicity of the liver (“bright liver”);

Increased echogenicity of the liver compared to the kidneys;

Blurred vascular pattern.

The advantages of ultrasound also include the ability to record the dynamics of signs of steatosis, including during treatment.

When performing a CT scan of the liver, the main signs indicating the presence of steatosis are:

Reducing the radiodensity of the liver, which is normally 50-75 units, to 3-5 units (when performing a CT scan without intravenous contrast enhancement, the density of the liver tissue with steatosis decreases by approximately 1.6 units for every milligram of TG contained in one gram of liver tissue) ;

The radiodensity of the liver with steatosis is less than the radiodensity of the spleen;

Visualization of intrahepatic vessels, portal and inferior vena cava as denser structures compared to liver tissue;

Crossing of areas of reduced radiocontrast by normal blood vessels of the liver (typical of focal fatty degeneration).

In general, CT is less informative than ultrasound for diffuse liver lesions, but it is the method of choice for focal diseases.

The advantages of modern high-field MRI compared to other imaging methods are: high tissue image contrast due to an advantageous signal-to-noise ratio, the ability to obtain a complete image of an organ in any projection, as well as large software resources used for differential diagnosis.

However, all visualization diagnostic methods, despite their fairly high information content, do not allow one to assess the presence of signs of steatohepatitis, the degree of its activity and the stage of fibrotic changes in the liver. Therefore, in order to verify the diagnosis, a puncture biopsy is necessary.

The value of liver puncture biopsy in clinical practice is controversial. On the one hand, only a liver biopsy makes it possible to make a differential diagnosis between steatosis and steatohepatitis, assess the stage of fibrosis and, based on histological data, predict the further course of the disease, as well as exclude other causes of liver damage. However, the lack of awareness among doctors about the feasibility and patients about the safety of the method is holding back the active introduction of puncture biopsy into practice.

In addition, the morphological criteria of NAFLD are still actively discussed. Until now, the classification proposed by Brunt E. (1999, 2001) has been widely used in practice, which subdivides NAFLD depending on the degree of steatosis, the activity of inflammation and the stage of liver fibrosis:

I. Degrees of large droplet steatosis:

Grade 0: no steatosis;
1st degree: steatosis up to 33% of hepatocytes;
Grade 2: steatosis 33-66% of hepatocytes;
Grade 3: steatosis more than 66%.

II. NASH grades:

1 degree (mild NASH) - steatosis of 1-2 degrees, minimal balloon degeneration in the 3rd zone of the acinus, lobular inflammation - scattered or minimal lymphoplasmacytic infiltration, portal inflammation is absent or minimal;
2nd degree (moderate NASH) - steatosis of any degree (large and small droplets), moderate balloon degeneration in the 3rd zone of the acinus, mild or moderate portal and lobular inflammation in the 3rd zone of the acinus, there may be perisinusoidal fibrosis;
3 degree NASH (severe NASH) - panacinar steatosis (mixed), severe balloon degeneration, severe lobular inflammation, mild or moderate portal inflammation.

III. Stages of fibrosis:

Stage 1 - perisinusoidal/pericellular fibrosis in zone 3 of the acinus, focal or widespread;
Stage 2 - perisinusoidal/pericellular fibrosis in zone 3 of the acinus, focal or widespread periportal fibrosis;
Stage 3 - focal or widespread bridging fibrosis;
Stage 4 - liver cirrhosis.

However, according to a number of authors, this classification does not reflect the whole range of morphological features detected in patients with NAFLD during histological examination. Recently, based on the existing classification, the NAFLD activity score (NAS) was developed and proposed, which represents a comprehensive assessment of morphological changes in scores and combines criteria such as steatosis (0-3), lobular inflammation (0-2) and balloon degeneration hepatocytes (0-2). A score of less than 3 allows us to exclude NASH, and a score of more than 5 indicates the presence of hepatitis in the patient. This scale is used primarily to assess the effectiveness of treatment for NAFLD, since it allows one to determine the reliability of the dynamics of morphological changes during therapy in a relatively short period of time.

In cases where a puncture biopsy is not possible, the diagnosis of NAFLD is established in accordance with an algorithm that allows step-by-step exclusion of other liver diseases (Table 2).

Due to the fact that all patients with MS are at risk for developing NAFLD, patients with obesity, type 2 diabetes or IGT, and lipid metabolism disorders require additional examination, including clinical, laboratory and instrumental methods for diagnosing NAFLD and, in particular, NASH. However, to date, NAFLD and its manifestations are not included either in the criteria for diagnosing MS or in the algorithm for examining patients suspected of having it (Table 3).

Screening of patients at the stage of preclinical manifestations of MS includes:

History (heredity, lifestyle, eating habits, physical activity);

Anthropometric measurements (body mass index (BMI), waist (WC) and hip (HC), WC/HC index);

Blood pressure (BP) monitoring, electrocardiographic study;

Assessment of lipid profile (TG, total cholesterol, high and low density lipoprotein cholesterol (HDL cholesterol, LDL cholesterol), plasma apo-B);

Determination of fasting glucose level, glucose tolerance test according to indications;

Fasting blood insulin.

Taking into account the frequency, role and significance of NAFLD, the algorithm for examining patients with MS should include clinical, laboratory and instrumental methods to assess the morphofunctional state of the liver:

Objective examination (assessment of hepatomegaly, splenomegaly, identification of telangiectasia, palmar erythema, etc.);

Clinical blood test (presence of thrombocytopenia, anemia);

Assessment of biochemical parameters reflecting the functional state of the liver (ALT, AST, GGTP, alkaline phosphatase, total bilirubin, prothrombin, proteinogram);

Ultrasound of the liver (degree of steatosis, hepatomegaly, portal hypertension);

Fibrogastroduodenoscopy (screening for varicose veins of the esophagus);

CT, MRI, radioisotope scan of the liver;

Liver puncture biopsy.

Mandatory indications for biopsy are:

Age over 45 years and chronic cytolysis of unknown etiology;

A combination of chronic cytolysis of unknown etiology with at least two manifestations of MS, regardless of age.

It is possible to assess the course of NAFLD based on histological examination of the liver. However, when a biopsy is not available, there are predictors that suggest a high risk of progression of NAFLD with the development of hepatitis and fibrosis, which were established during statistical processing of the results of a large number of observations.

These include:

Age over 45 years;

Female;

BMI more than 28 kg/m2;

Increase in ALT activity by 2 times or more;

TG level more than 1.7 mmol/l;

Presence of arterial hypertension;

Type 2 diabetes;

IR index (HOMA-IR) more than 5.

Identification of more than 2 criteria indicates a high risk of liver fibrosis.

To formulate a full-fledged clinical diagnosis, it is necessary to take into account the data of clinical, laboratory and instrumental examinations, identifying factors for the unfavorable course of the disease and other components of MS. Since the diagnosis of “non-alcoholic fatty liver disease” is not yet available in ICD-10 (WHO, 1998), its formulation by practitioners can be made taking into account the rules for diagnosing alcoholic liver disease and viral hepatitis. In the diagnosis, it is better to indicate in the first place the nosological unit against which NAFLD developed, followed by the form of the disease (hepatosis or NASH), the degree of steatosis (according to ultrasound), hepatitis activity and the stage of fibrotic changes in the liver in the case of hepatobiopsy. If a morphological study has not been performed, the acceptable conclusion, as with other liver diseases, is: unidentified fibrosis. Examples of diagnostic reports:

Obesity II degree. Non-alcoholic fatty liver disease: grade II steatosis (according to ultrasound), unknown fibrosis (no biopsy was performed).

Stage II hypertension. Stage I arterial hypertension, high risk. Secondary dyslipoproteinemia, combined. Diabetes mellitus, newly diagnosed. Obesity I degree. Non-alcoholic fatty liver disease: non-alcoholic steatohepatitis, moderate activity, stage 2 fibrotic changes (periportal fibrosis).

Diabetes mellitus type 2, compensated. Non-alcoholic fatty liver disease: non-alcoholic steatohepatitis, severe activity (severe course), severe (bridging) fibrosis.

Diabetes mellitus type 2, decompensated. Liver cirrhosis as a result of severe non-alcoholic steatohepatitis, subcompensated, Child class B, severe portal hypertension, ascites, grade II esophageal varices.

Treatment of NAFLD

Due to the high probability of an unfavorable course of NAFLD, especially in combination with other manifestations of MS, all patients, regardless of the severity of the disease, require dynamic monitoring and treatment. However, standardized therapeutic approaches to the management of patients with NAFLD have not yet been developed.

The used directions of therapy for patients with NAFLD are based on the mechanisms of disease development, which primarily include IR syndrome and oxidative stress, therefore the most important tasks for this category of patients are:

correction of metabolic disorders:

Losing body weight (diet and exercise);

Increasing the sensitivity of cellular receptors to insulin (metformin, thiazolidinediones);

Decrease in TG levels (fibrates, statins);

Reduced concentration of TNFa (pentoxifylline);

Antihypertensive therapy (angiotensin II receptor antagonists);

treatment of oxidative stress:

Antioxidants and hepatoprotectors (vitamin E, silibinin, betaine, N-acetylcysteine, ursodeoxycholic acid (UDC), a-lipoic acid (ALA));

restoration of intestinal microbiocenosis (eubiotics, probiotics, prebiotics).

Diet. Taking into account modern ideas about the etiology, pathogenesis and progression factors of NAFLD, the following dietary principles are recommended for patients:

For patients with overweight and obesity - a decrease in the total energy value of the diet. Daily caloric intake is selected individually depending on body weight, age, gender, level of physical activity using special formulas. First, calculate the number of calories needed for basal metabolism:

for women:

18-30 years: (0.06 × weight in kg + 2.037) × 240
31-60 years: (0.034 × weight in kg + 3.54) × 240
over 60 years old: (0.04 × weight in kg + 2.76) × 240

for men:

18-30 years: (0.06 × weight in kg + 2.9) × 240
31-60 years: (0.05 × weight in kg + 3.65) × 240
over 60 years old: (0.05 × weight in kg + 2.46) × 240.

The resulting value is multiplied by the coefficient of physical activity (1.1 - low activity, 1.3 - moderate, 1.5 - heavy physical work or active sports) and the calorie content of the daily diet is obtained. To reduce body weight, 500-700 kcal are subtracted from the calculated daily energy expenditure. However, the minimum daily calorie intake should be at least 1200 kcal for women and at least 1500 for men. It has been proven that a decrease in body weight by 5-10% is accompanied by a decrease in hepatosplenomegaly, ALT, AST activity and correlates with regression of liver steatosis. It should be taken into account that rapid weight loss can lead to the development of “acute” NASH with the formation of portal fibrosis, central necrosis against the background of a significant increase in inflammatory activity due to an increase in the flow of FFA into the liver against the background of peripheral lipolysis. For obese patients with NAFLD, it is safe and effective to reduce body weight by 500 g per week for children and by 1600 g per week for adults.

Limiting fats to 25-30% of the total energy value of food;

The ratio of polyunsaturated and saturated fatty acids (FA) in food is more than 1 (exclusion of butter, animal fat, hard margarine, etc., consumption of foods rich in polyunsaturated fatty acids - vegetable oil, seafood, fish, poultry, olives, nuts, taking into account energy needs);

Reducing the consumption of foods high in cholesterol (no more than 300 mg per day) - eliminating offal (liver, kidneys), caviar, egg yolk, raw smoked sausages, fatty meats and dairy products;

Exclusion of products prepared as a result of food processing such as frying, deep frying, etc.;

Enrichment of food with vitamins and natural prebiotics (fruits, Jerusalem artichoke, leeks, artichokes);

For patients with IGT and type 2 diabetes, a diet excluding simple carbohydrates and limiting complex carbohydrates is relevant, which helps achieve metabolic control.

. Physical activity is a mandatory condition for the treatment of patients with NAFLD. It has a positive effect on weight loss and insulin sensitivity, while increasing the supply of FFAs into muscle tissue, where they are oxidized, thereby reducing IR. The degree of reduction in IR, as a rule, correlates with the intensity of physical exercise, which is recommended to be performed at least 3-4 times a week, lasting 30-40 minutes.

Increased sensitivity of cellular receptors to insulin . Basic medications for the treatment of IR syndrome in patients with NAFLD may include insulin sensitizers - biguanides (metformin) and thiazolidinediones (pioglitazone, rosiglitazone) - drugs that increase the sensitivity of cellular receptors to insulin. Experience with the use of these drugs indicates a positive effect on the clinical and morphological manifestations of NAFLD in the form of a decrease in the activity of cytolytic syndrome indicators, the degree of steatosis and inflammation. But in general, the issue of using these drugs in patients with NAFLD requires further research, which is due to the lack of adequate methods for monitoring the effectiveness of treatment (hepatobiopsy) in the work performed.

Lipid-lowering drugs . Considering the pathogenesis of the disease, the use of lipid-lowering drugs from the group of fibrates may be effective in patients with NAFLD. However, the results of a study with the administration of clofibrate to patients with NAFLD showed its ineffectiveness. We should not forget about the possibility of developing fibrate-induced hepatitis. Statins also have a number of contraindications associated with their hepatotoxic effects. In general, the data from the work performed are contradictory and indicate the need for further study of the possibility of using these drugs in patients with NAFLD.

Pentoxifylline. A decrease in the concentration of tumor necrotizing factor-a (TNFa) is important for the progression of NAFLD. Possessing high biological activity, TNFa enhances IR and leads to the development of oxidative stress. A decrease in its level in the blood is associated with regression of clinical and morphological manifestations of NAFLD. A similar effect was found with pentoxifylline. The administration of this drug to patients with NASH at a daily dose of 1200 mg for 12 months was associated with a decrease in cytolytic syndrome and a significant improvement in histological parameters in 67% of patients.

Angiotensin II receptor antagonists. The formation of this approach is due to the role of angiotensin in the progression of NASH. It has been established that, by promoting the proliferation of myofibroblasts, cell migration, the synthesis of collagen and pro-inflammatory cytokines, it activates the processes of fibrogenesis in the liver. Therefore, the use of angiotensin receptor blockers in patients with NAFLD is currently being investigated. Thus, taking losartan in patients with NASH and arterial hypertension at a daily dose of 50 mg for 38 weeks led to a significant decrease in ALT and GGTP, which was combined with a decrease in the degree of steatosis and inflammatory activity.

Antioxidants. The use of antioxidants in patients with NAFLD is justified by the presence of oxidative stress, which is confirmed by an increase in the plasma of oxidative stress marker, thioredoxin, and a decrease in the concentration of antioxidant factors in patients with NASH. The possibility of using vitamin E is currently being actively studied, the effectiveness of which has been demonstrated in a number of studies. There are also a number of foreign and domestic works devoted to assessing the effect of UDC on the morphofunctional state of the liver. The mechanisms of action of this hydrophilic acid are related to the fact that, by normalizing the hepatoenteric circulation of bile acids and a number of biologically active substances, displacing toxic bile acids, it helps eliminate excess cholesterol in hepatocytes, by reducing its synthesis and absorption from the intestine. UDC also has a cytoprotective and antiapoptotic effect, preventing the development of oxidative stress, which makes it possible to use it at both stages of NAFLD.

With regard to ALA, it has been established that it has a pleiotropic effect on the entire body, having a positive effect on energy, lipid (inhibits cholesterol synthesis, suppressing the release of FFA from adipose tissue, which prevents the development of hepatocyte steatosis) and carbohydrate (reduces IR, enhances the uptake and utilization of glucose cell, increases the sensitivity of cellular receptors to insulin) types of exchanges.

In addition, ALA, having a low redox potential, has a powerful antioxidant effect, acting directly on the liver, helps to increase detoxifying substances in hepatocytes (restores glutathione) and improves morphological changes.

Restoration of intestinal microbiocenosis. Unfortunately, most of the studies confirming the pathogenetic role of intestinal dysbiosis in the formation of NAFLD and the effectiveness of antibacterial drugs in the treatment of this nosology date back to the 80-90s of the last century.

Therefore, the issue of intestinal sanitation with antibacterial drugs remains open. Antibiotics are recommended only in the presence of verified sensitive opportunistic flora in the intestine or the formation of a disease after surgical treatment in the abdominal cavity, for example, “adductor loop syndrome.” The advantage of choice in this case belongs to drugs that have the ability to accumulate well in bile with the effect of secondary passage through the gastrointestinal tract, which include first-generation fluoroquinolones (ciprofloxacin). Intestinal antiseptics, such as metronidazole or nifuroxazide, and drugs that are not absorbed in the intestine, such as rifaximin, may also be used.

In all other cases, when there are no indications for the use of antibiotics, intestinal sanitation in patients with NAFLD should be carried out with prebiotics, and the drug of choice in this case is Eubicor. Its advantage is its balanced composition, which includes dietary fiber and wine yeast ( S. vini). In addition to a powerful prebiotic effect, Eubicor has good sorption properties, which allows not only to restore normal microflora, but also to carry out detoxification. According to research results, taking Eubicor in this category of patients contributed to an additional reduction in dyslipoproteinemia and an increase in insulin sensitivity.

Treatment of non-alcoholic gastrointestinal tract

In general, the requirements for drugs used in the treatment of NAFLD are quite high. First of all, they should be as safe as possible from the point of view of hepatotoxicity; their positive effect on improving clinical, laboratory and morphological changes in the liver is also desirable.

Our own experience in treating patients with NAFLD at the stage of hepatosis consists of using a combination of ALA with Eubicor. ALA (drug "Berlition", manufacturer - Berlin-Chemie, Germany) was prescribed 600 units intravenously for 14 days, with a transition to oral administration in the same daily dose, once for 6 months. Eubicor was prescribed 2 sachets 3 times a day with meals. The results of the work showed a positive effect of Berlition and Eubicor not only on lipid and carbohydrate metabolism, but also on the degree of fatty degeneration in the liver according to the results of ultrasound and morphological studies. The positive dynamics of these changes is important both for the formation of systemic IR, which is the main cause of the development of MS, and for the course of NAFLD itself and the development of NASH. Therefore, these drugs, along with non-drug therapy, can be considered as a means of basic therapy for the first stage of NAFLD - GL.

Treatment of NASH

When NASH developed in patients, therapy for the disease was enhanced with an additional combination of metformin (the drug "Siofor", manufactured by Berlin-Chemie, Germany) at a dose of 1500 mg per day with UDC (the drug "Ursosan" from PRO.MED.CS Praha a.s.) at a dose of 15 mg per 1 kg of body weight, with a single dose one hour after dinner. The duration of treatment was selected individually; as a rule, it was at least 6 months, sometimes reaching 12 months or more. The duration of the course depended on the severity of clinical manifestations, compliance and dynamics of laboratory and instrumental parameters during treatment. The administration of these drugs was accompanied by a decrease not only in the clinical and laboratory manifestations of the disease, but also significantly contributed to the improvement of the histological picture of the liver. At the same time, combination therapy in this category of patients was the method of choice, since it was in the group receiving simultaneously Siofor, Berlition and Ursosan that the dynamics of indicators of the syndromes of cytolysis, cholestasis, as well as fat and carbohydrate metabolism were more significant. During treatment, patients with NASH also experienced a reverse development of fatty degeneration, a significant decrease in the severity of inflammatory changes, and no progression of the stage of fibrosis in the liver. Thus, combination therapy affects the main etiopathogenetic mechanisms of the formation of metabolic disorders, leads to an improvement in lipid and carbohydrate metabolism in the form of normalization of HDL, TG levels and the IR index in patients with NASH.

UDC (Ursosan) 15 mg/kg/day.

Lipid-lowering diet;

Physical activity - at least 3-4 times a week for 30-40 minutes;

Compensation for diabetes (against the background of a diet in combination with oral hypoglycemic drugs or insulin);

Eubicor 2 sachets 3 times a day;

Metformin (Siofor) in an individually selected dosage depending on the level of glycemia (do not prescribe to patients with advanced forms of NAFLD, with liver failure due to the risk of developing lactic acidosis);

ALA (Berlition) 600 units per day;

UDC (Ursosan) 15 mg/kg/day.

Arterial hypertension in patients with NAFLD is one of the risk factors for the progression of fibrosis, therefore, preference when choosing an antihypertensive drug for correcting blood pressure (BP) levels should be given to drugs from the group of angiotensin II receptor antagonists. Recommended algorithm for choosing therapy for patients with NAFLD and arterial hypertension:

Thus, timely diagnosis of NAFLD and identification of possible risk factors for the unfavorable course of the disease are important, since taking them into account makes it possible to select an adequate treatment method that prevents further progression of NAFLD. In this regard, all patients with MS who have a high probability of having NAFLD and especially NASH should be examined to assess the morphofunctional state of the liver. At the same time, despite the fact that the formation of standards for the diagnosis and treatment of NAFLD remains an unresolved issue, medical specialists, based on the existing need, can use the proposed algorithms in their practice.

For questions regarding literature, please contact the editor.

S. N. Mehdiev
V. B. Grinevich, Doctor of Medical Sciences, Professor
Yu. A. Kravchuk, Candidate of Medical Sciences
A. V. Braschenkova
VMA named after. S. M. Kirova, Saint Petersburg

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, which leads to decreased quality of life, disability and death. Around the world, about 10–40% of people suffer from NAFLD. The main danger is the transformation of the pathology into non-alcoholic steatohepatitis with the development of liver failure and malignancy of the process.

The term “NAFLD” refers to clinical and morphological changes in the structure of the liver such as steatosis, fibrosis and cirrhosis, which occur in patients who do not drink alcohol in toxic doses. The disease most often affects middle-aged women with metabolic syndrome.

Stages

NAFLD manifests itself in increased fat deposition in the liver, accompanied by a decrease in the sensitivity of peripheral tissues to insulin. The diagnosis is made when steatosis is detected in more than 5% of liver cells on a biopsy. Before making a diagnosis, it is necessary to exclude other causes of liver damage, primarily alcohol consumption in hepatotoxic doses (more than 30 g of ethanol per day for men and 20 g per day for women). Excessive consumption of ethanol-containing drinks indicates alcoholic liver disease.

The development of NAFLD is divided into 4 successive stages:

Liver steatosis (accumulation of adipocytes and fat droplets in hepatocytes and liver parenchyma). If NAFLD is suspected, steatosis should be confirmed. This stage can be identified using ultrasound, CT or MRI. Ultrasound is more readily available, but abdominal MRI can reliably diagnose moderate to severe steatosis and provides additional information about the hepatobiliary system.
Steatohepatitis (attachment of the inflammatory process to stage 1). Detection of steatohepatitis indicates an increased risk of progression of the disease to subsequent stages and serves as a reason for more careful and frequent monitoring and intensive treatment. Reliable diagnosis of steatohepatitis is possible by performing a liver biopsy.
Liver fibrosis (with a long-term, sluggish inflammatory process, hepatocytes begin to be replaced by connective tissue elements, and foci appear in the form of fibrous constrictions). The occurrence of fibrosis is an important factor influencing the prognosis, outcomes and mortality of patients with NAFLD. The presence of severe fibrosis is an indication for hospitalization, a thorough examination of the liver, including a biopsy, and the initiation of intensive drug therapy. Regular monitoring of fibrosis progression is necessary.
Liver cirrhosis (an increase in the amount of scar tissue in the liver parenchyma with the development of progressive liver failure). Cirrhosis is a terminal stage of the disease, irreversible damage to the liver parenchyma. The only effective treatment for this condition is liver transplantation.

Symptoms

The disease is asymptomatic and is most often detected by chance during an ultrasound of the abdominal cavity or when increased activity of liver enzymes is detected according to a biochemical blood test.

At the stage of fibrosis and cirrhosis, heaviness and discomfort in the right hypochondrium, weakness, fatigue, itching, yellowness of the skin, mucous membranes and sclera, bitterness and dry mouth may occur. Advanced liver failure manifests itself in the form of ascites, hydrothorax and hydropericardium (accumulation of non-inflammatory fluid in the abdominal cavity, chest and cardiac sac), dilation of the saphenous veins of the anterior abdominal wall, edema of the lower extremities, and enlarged spleen.

Causes of the disease

Poor lifestyle is the main cause of NAFLD. The most common risk factors are a diet consuming excess calories, saturated fats, easily digestible carbohydrates and fructose, and low physical activity.

In some cases (especially among children and adolescents), a hereditary predisposition to NAFLD may be confirmed, resulting from defects in the genetic material (PNPLA3 and TM6SF2 gene).

There is a close connection between NAFLD and impaired glucose utilization by hepatocytes, muscle and adipose tissue cells, as well as metabolic syndrome.

Metabolic syndrome is diagnosed when three of the five criteria associated with insulin resistance are met: type 2 diabetes mellitus or fasting hyperglycemia, an increase in plasma triglyceride levels of more than 1.7 mmol/l, a decrease in HDL cholesterol of less than 1.0 mmol/l in men or less 1.3 mmol/l in women (anti-atherogenic fraction of cholesterol), abdominal obesity (waist circumference more than 94 cm in men and more than 80 cm in women) and arterial hypertension.

If a patient has metabolic syndrome, NAFLD should be suspected. Deposition of triacylglycerols in the liver parenchyma leads to disturbances in energy metabolism and a decrease in insulin function, resulting in hyperglycemia, hypertriglyceridemia and hyperinsulinemia. Progression of liver damage leads to worsening insulin resistance. The HOMA-IR index is used to screen for insulin resistance.

Abdominal obesity (increased waist circumference) indicates the presence of NAFLD. The severity of the disease is also aggravated by diseases associated with obesity: polycystic ovary syndrome, obstructive sleep apnea, hypogonadism, diabetes mellitus.

Patients suffering from diabetes mellitus are characterized by atherogenic dyslipidemia, elevated levels of liver transaminases and accumulation of fatty droplets in the liver. On the other hand, diagnosed NAFLD is associated with a high risk of diabetes mellitus, therefore, such patients are recommended to undergo an oral glucose tolerance test to detect disorders of carbohydrate metabolism.

Possible complications

Main complications of NAFLD:

Cardiovascular diseases. Excess weight, diabetes mellitus, and dyslipidemia accompanying NAFLD are risk factors for cardiovascular pathology. Myocardial infarction and stroke are more common causes of death than liver failure in NAFLD.
Hepatocellular carcinoma is a malignant tumor into which cirrhosis can transform; the incidence is 7.6% over 5 years.
Concomitant diseases of other organs: chronic renal failure, colorectal cancer, osteoporosis, hypovitaminosis D, lipodystrophy.

Diagnostics

If NAFLD is suspected, the following standard diagnostic tests are performed:

In patients without signs of progression of liver failure, monitoring of laboratory and ultrasound parameters should be carried out every 2–3 years. Patients in the stage of fibrosis require annual monitoring, and in case of liver cirrhosis, the dynamics are assessed every 6 months.

The progression of the disease in the first stage is slow, corresponding to one stage every 14 years. Starting from the second stage, the disease progresses by one stage every 7 years, the rate doubles in the presence of arterial hypertension.

Treatment methods

The main goal of treatment is to slow the progression of NAFLD to cirrhotic disease. To do this, you need to take the following measures:

Changing your diet.
Normalization of body weight, possible use of drugs that reduce appetite (orlistat).
Quitting bad habits or reducing the intensity of smoking and drinking alcohol.
Aerobic exercise and strength training. With active exercise, the supply and utilization of free fatty acids in muscle tissue increases, which leads to a decrease in insulin resistance and weight loss. It is recommended to carry out training 3-5 times a week for at least 30 minutes.
Treatment of diabetes mellitus (drug of choice - metformin).
Antioxidants (tocopherol - vitamin E 800 mg per day).
Cytoprotectors (ursodeoxycholic acid 500–750 mg per day, obeticholic acid, omega-3-polyunsaturated fatty acids 1000 mg per day).
Lipid-lowering therapy (statins: Atorvastatin, Rosuvastatin, Simvastatin, bile acid sequestrants, Ezetimibe).
Treatment of arterial hypertension with angiotensin-converting enzyme inhibitors: Enalapril, Perindopril, Ramipril; angiotensinogen receptor blockers: Losartan, Valsartan, Telmisartan).
Bariatric surgery (surgeries aimed at reducing the mass of adipose tissue are indicated for morbid obesity with a body mass index of more than 50 kg/m2).
Liver transplantation is performed in the terminal stages of cirrhotic lesions refractory to drug treatment.

Antihyperglycemic, lipid-lowering and antihypertensive drugs are prescribed for life.

The duration of therapy with cytoprotectors and antioxidants is discussed individually.

Most patients are treated on an outpatient basis. The indication for hospitalization is a liver biopsy to clarify the diagnosis, severe liver failure, complicated liver cirrhosis.

Diet

Meals are fractional, in small portions 4–5 times a day. Principles and recommendations of therapeutic nutrition for NAFLD:

reducing the consumption of saturated fats to 25–30% of total food;
replacing quickly digestible carbohydrates (sweets, wheat flour, pasta, white bread) with complex ones (whole grain bread, cereals, porridges);
polyunsaturated fatty acids (nuts, olives, fatty sea fish and seafood, vegetable oils) should prevail over saturated ones (fatty meat, butter, lard, margarine);
a diet with reduced cholesterol (refusal to consume animal fats, egg yolks);
refusal of sweet carbonated drinks, fruit juices;
Preferred food processing methods: boiling, baking, steaming.

Prognosis and prevention

With the initial stages of the disease and timely treatment, the prognosis is favorable.

Monitoring patients with NAFLD:

consultation with a gastroenterologist to assess the progression of the disease - every 6 months;
general blood test, biochemical blood test, lipid spectrum - every 6 months;
observation by an endocrinologist, study of fasting blood glucose levels, glycated hemoglobin, correction of glucose-lowering therapy - every 6 months;
Ultrasound of the abdominal organs - every 6 months;
indirect elastography of the liver for hidden fibrosis - once a year;
measuring blood pressure, weighing, calculating body mass index - at every medical consultation.

Prevention consists of maintaining a healthy lifestyle, maintaining normal body weight, and treating concomitant diseases.

is a descriptive term used to identify the accumulation of fat droplets in the liver cells and includes a set of specific symptoms that characterize the accumulation of fat and inflammation of the liver tissue.

Most often, this process is diffuse in nature, i.e. covers the entire liver, but there may also be a local detection of the process (lipoma) - during ultrasound examination of the abdominal organs (ultrasound). In the presence of non-alcoholic steatohepatitis a diagnosis can be made - fatty liver degeneration, chronic hepatitis of unspecified etiology, unspecified cirrhosis of the liver. The prevalence ranges from 10 to 40%.

Risk groups for liver steatosis

Patients with metabolic syndrome (type 2 diabetes mellitus, obesity, increased cholesterol and triglycerides).
Patients with type 2 diabetes mellitus (in 70-100% of cases).
Obese patients (in 30-100% of cases).
Patients with elevated cholesterol and triglyceride levels (20-90%).
Patients with diabetes mellitus and obesity (steatohepatitis is detected in 50% of cases, liver cirrhosis in 19-20% of cases).

Most often, patients aged 40-60 years are susceptible to the disease, but in children with normal body weight non-alcoholic fat disease detected in 2.6%, in obese children - in 22.5-52.8%.

Depending on gender, the disease predominates in women - 53-85%. First stage – fatty liver disease– 5 times more common in men, and steatohepatitis– 3 times more often in women.

Causes of non-alcoholic steatohepatitis

Taking certain medications (hormones (glucocorticosteroids), estrogens, nefidipine, methotrexate, aspirin, diltiazem).
Eating disorders (fasting, rapid weight loss, low protein diet).
Surgical interventions (stomach and intestinal operations).
External exposure to toxic substances (organic solvents, phosphorus, poisonous mushrooms).
Intestinal diseases (inflammatory diseases, malabsorption, excessive growth of bacteria in the intestines).
Insulin resistance is a decrease in the biological response to one or more effects of insulin.

The development of insulin resistance is facilitated by a hereditary factor - a predisposition to diabetes mellitus, detection of diabetes mellitus in close relatives, as well as excess caloric nutrition and low physical activity. These factors themselves contribute to increased obesity and fat accumulation in liver tissue. In approximately 42% of patients, risk factors for developing the disease cannot be identified.

Symptoms of non-alcoholic fatty liver disease

Most patients have no complaints. There may be discomfort and heaviness in the abdomen, weakness, increased fatigue, heaviness in the right hypochondrium, nausea, belching, and loss of appetite.

Upon examination, an increase in the size of the liver is revealed. Often there is suspicion of non-alcoholic fatty liver disease Diagnosed by performing an ultrasound of the abdominal organs or a biochemical blood test.

Diagnosis of non-alcoholic fatty liver disease

IN biochemical blood test There is an increase in liver enzymes ALT and AST to 4 norms, alkaline phosphatase to 2 norms.

At ultrasound examination (ultrasound) The information content of the method decreases in obese patients.

Computed tomography (CT) – allows you to accurately assess the degree steatosis, the sensitivity and specificity of the method is 93-100%.

Magnetic resonance imaging (MRI) – provides a complete image of the organ in any projection, has a high agreement with the data of histological examination.

Liver elastography – has higher accuracy in advanced stages of liver damage (fibrosis).

Prognosis for non-alcoholic fatty liver disease

With progression non-alcoholic fatty liver disease There is a higher risk of developing cardiovascular diseases, atherosclerosis, metabolic syndrome, and type 2 diabetes.

Overall for non-alcoholic fatty liver disease characterized by a benign course. The development of liver cirrhosis is observed in only 5% of cases. The prognosis of the disease is influenced by such factors as the presence of concomitant pathology, primarily obesity, diabetes mellitus, dyslipidemia, arterial hypertension and adequate correction of metabolic disorders.

Treatment of liver steatosis

Weight loss, lifestyle changes (diet and exercise).
Treatment of metabolic syndrome.
Use of hepatoprotectors.
Restoration of intestinal microflora.
Correction of lipid metabolism.

When the doctor and patient work together, treatment liver steatosis goes well. GUTA CLINIC has its own extensive diagnostic base for identifying non-alcoholic fatty liver disease at any stage. We use expert-level equipment from the world's leading manufacturers - leaders in the production of medical devices. Highly qualified doctors of GUTA CLINIC, candidates and doctors of medical sciences, using their rich clinical experience, will prescribe an individual regimen treatment of liver steatosis and help you stay healthy!