Alcohol abuse, or chronic alcohol intoxication (CAI), is a severe social and medical problem of global importance. In the 2nd half of the 20th century. In all countries of the world, there has been a significant increase in the consumption of alcoholic beverages, leading to an increase in associated pathologies of internal organs. For example, in Germany, the prevalence of alcoholic cirrhosis (AL) increased by 225% between 1978 and 1985. In Russia, on the last 10th anniversary of the 20th century. Alcohol abuse has become a national disaster. Among European countries, Russia has become the absolute leader in alcohol consumption per capita. One working adult consumed about 25 liters of ethanol per year in 1998, with a significant share coming from spirits and products with high levels of toxic alcohol substitutes. Over the last 10 years, specific alcohol consumption in Russia has decreased slightly and in 2012 amounted to less than 14 liters per capita. However, in the structure of alcohol consumed, the share of strong alcohol remains the largest among European countries. In most European countries, with the exception of Ireland, Finland and the UK, no more than 3.5 liters of ethanol per capita per year is consumed with strong alcoholic beverages (Fig. 1).
However, in the European Union, alcohol abuse is the third most common cause of loss of health after cardiovascular diseases and smoking; damage to internal organs due to CAI is much more likely than in the world to cause death (4.6 and 3.8% of all lethal deaths, respectively). outcomes) or disability (11.5 and 6.5% of DALYs (disability-adjusted life year), respectively. About 10% of DALYs due to alcohol abuse are due to alcoholic liver disease (ALD). However, in a number of countries, for example, in Portugal, this figure is significantly higher and amounts to 31.5% of alcohol-related disability.
The active implementation of socio-economic methods of combating CAI (increasing the cost of alcohol, promoting weak alcohol, banning sales to minors, etc.), as well as promoting a healthy lifestyle, have led over the past 30 years to a significant decrease in the frequency of lethal ALD in many countries Europe, for example in France and Italy. Between 1970 and 2004, mortality associated with ALD in Europe decreased by 60% (from 13.8 to 8.01 per 100 thousand people under 65 years of age). At the same time, the incidence of fatal ALD is steadily increasing in the UK, Ireland, Finland, Eastern Europe and Russia. This growth, in addition to the also widespread habit of strong alcohol in these countries, is facilitated by the global economic crisis of recent years, social problems and unemployment in Eastern Europe for more than 20 years. It has been proven that a 3% increase in unemployment leads to a 28% increase in mortality from diseases associated with alcohol abuse.
Since the highest mortality rate is characteristic of alcoholic cirrhosis, this indicator serves as a kind of indicator of alcohol consumption in each specific country. Among European countries, the highest mortality from cirrhosis was recorded in 1997-2001. in Great Britain - 14.1 per 100 thousand adult population. In Russia, the mortality rate from alcoholic cirrhosis was and remains significantly higher - in 2010 in large cities it reached 50 per 100 thousand population. It is known that the road to cirrhosis begins with the development of potentially reversible steatosis (80-90% of patients with CAI) and chronic steatohepatitis (30-40% of patients with CAI), against the background of which fibrosis and cirrhosis gradually form, chronic liver failure and portal hypertension develop (15-20% of patients with CAI).
In CAI, the progression of ALD from steatosis to cirrhosis is a process that correlates with the amount, duration and nature of alcohol consumption. However, consistent scientific data regarding the dose of alcohol directly associated with the risk of developing cirrhosis or death has not yet been obtained: a dangerous dose varies from 25 to 100 g of pure ethanol per day. On average, taking 60-80 g of ethanol per day for men and more than 20 g per day for women for more than 10 years is associated with a high risk of developing ALD. The relative risk of ALD and death from cirrhosis increases with increasing alcohol dose: at 50 g/day it increases 2 times, and at 100 g/day it increases 5 times in both men and women, regardless of age and presence or the absence of comorbid pathology of internal organs. On the other hand, regular consumption of small doses of ethanol (up to 15 g/day for men and up to 10 g/day for women), according to a number of researchers, protects against the development of CVD, especially in old age. Moreover, a number of studies have shown that such “light” alcohol consumption can prevent the development of insulin resistance, incl. in obese patients.
The mechanism of formation of systemic metabolic disorders
and pathologies of internal organs
with alcohol abuse
The high incidence of ALD in alcohol abuse is due to the fact that the liver is an organ that metabolizes 75-98% of ethanol entering the body. In hepatocytes and cells of other tissues, ethanol is oxidized to acetaldehyde under the action of the cytosolic enzyme alcohol dehydrogenase (ADH) and the microsomal enzyme cytochrome P-450 2E1. Acetaldehyde is converted to acetate by the enzyme acetaldehyde dehydrogenase. Both of these reactions produce reduced NADH (NAD+H: C2H5OH+2NAD→ C2H4O+2NAD+H) and reduce the oxidative potential of the hepatocyte - with daily intake of large doses, oxidative stress and hypoxia of the hepatocyte develop, which disrupt the entire biochemistry of the cell. Next, acetate is metabolized in the carboxylic acid cycle, resulting in the formation of carbon dioxide and energy: C2H4O→CO2+H2O+energy (Fig. 2).
With rare consumption of large amounts of ethanol, metabolic acidosis, electrolyte disturbances, as well as the neurotropic and vascular effects of alcohol as a universal vasodilator and sedative agent are most “responsible” for direct tissue damage and intoxication (hangover).
With CAI, disorders of tissue biochemistry become permanent (Table 1) - the center of metabolic disorders are the consequences of the oxidation of large amounts of ethanol, acidosis and accumulation of acetaldehyde. An excess of “light” alcoholic carbohydrates leads to an increase in the synthesis of free fatty acids, and the accumulation of acetaldehyde and oxidative stress leads to a slowdown in β-oxidation of fatty acids. Both processes result in the accumulation of toxic fatty acids, which the hepatocyte converts into triglycerides, as well as cholesterol - steatosis develops. Steatohepatitis and deep stereotypical disturbances in the biochemistry of hepatocytes and cells of other target organs (cardiomyocytes, neurons, striated muscle cells) develop with “severe” CAI. Due to an imbalance between the formation and degradation of acetaldehyde and its accumulation in the cytosol, the destruction of polyunsaturated fatty acids that make up the phospholipids of cell membranes occurs. As a result, the activity of the associated Na+- and Ca++-dependent transport enzyme systems is disrupted, and the structure and antigenic properties of membrane receptors change.
The constant need to oxidize large amounts of ethanol leads to the induction of P-450 2E1 and stimulation of oxidative stress with the formation of large amounts of reactive oxygen species. Under conditions of deficiency of intracellular antioxidant systems (glutathione peroxidase, superoxide dismutase and catalase), oxygen radicals activate lipid peroxidation, reduce the activity of proteasomes, which disrupts the catabolism of damaged proteins and promotes the accumulation of cytokeratin - the formation of Mallory bodies. Toxic products of LPO (malondialdehyde) further increase glutathione deficiency - abnormal mitochondria are formed. Homocysteine ​​accumulates in the cell, further potentiating the degradation of the endoplasmic reticulum. Under the influence of LPO, complement and TNF receptor 1 (TNF-R1) are activated, which activates caspases that trigger hepatocyte apoptosis. Reactive oxygen species and LPO products participate in the formation of protein carbonyls and react with DNA and structural proteins, converting them into antigens that activate immune inflammation (Fig. 3).
Initially, inflammation in the liver parenchyma is aseptic. In response to damage to hepatocytes and the formation of antigens in them, the innate immune system triggers inflammation, and then fibrogenesis through humoral factors (complement, interferons) and the activity of various phagocytic leukocytes - neutrophils, monocytes, lymphocytes and specialized macrophages that provide the secretion of inflammatory mediators (Kupffer cells ). Recent studies have convincingly shown that the immune response in the liver parenchyma is also powerfully stimulated by lipopolysaccharides of bacterial origin entering the liver from the intestine. Through stimulation of pattern recognition receptors (PRRs) and toll-like receptors (TLRs) on the surface of Kupffer cells, lipopolysaccharides activate the secretion of pro-inflammatory mediators: cytokines (the most active are TNFα and IL-1) and chemokines (IL-8, MCP-1. CXC) . Activation of Kupffer cells also occurs under the direct influence of the complement system (mainly its C3 and C5 components). Sensitized Kupffer cells regulate another immune link involved in maintaining both inflammation and regeneration of liver cells - the IL-1 and IL-6 they secrete regulate the differentiation of CD4+/CD8 T-helper lymphocytes (cellular immunity of the intestinal mucosa). These lymphocytes in turn secrete IL-17 and IL-22. IL-17 activates stellate cells that produce chemoattractants for neutrophils actively migrating into the liver parenchyma during steatohepatitis - the number of neutrophils in the portal tracts serves as a histological marker of the activity of alcoholic hepatitis. Bacterial lipopolysaccharides can also promote fibrogenesis by stimulating the secretion of platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-β) by stellate cells.
In addition to pro-inflammatory, sensitized Kupffer cells also secrete protective anti-inflammatory and antifibrotic cytokines IL-6, IL-10, IL-22, which contact the STAT protein system, which stimulates DNA repair and hepatocyte proliferation.
The most characteristic histological signs of alcoholic hepatitis are the presence of Mallory bodies against the background of balloon dystrophy, steatosis and necrosis of hepatocytes located mainly in the center of the hepatic lobule (zone III). Characteristic features include infiltration of the hepatic lobule by macrophages and segmented leukocytes, zone III edema, steatosis and collagen deposition with a predominantly perisinusoidal arrangement of fibers. In all cases, even against the background of severe fibrosis, with CAI, histological preparations show signs of steatosis and intrahepatic cholestasis of varying severity (Fig. 4-7).
The most severe disturbances in the biochemistry and structure of the liver parenchyma develop with “severe” CAI. First of all, it includes one of the most toxic scenarios for the liver of alcohol abuse - frequent drinking (binge-drinking, too much too fast), during which during the first two hours >70 ml of ethanol is taken for men and >55 ml for women - dose that creates a toxic concentration of ethanol in the blood (≥0.08). This mode of alcoholization becomes especially dangerous when drinking alcohol on an empty stomach, since it leads to metabolic disorders that are traumatic for the cells of the liver, central nervous system (CNS) and myocardium: hypoglycemia, glycogenolysis, metabolic acidosis and a hypermetabolic state - the main triggers of oxidative stress and inflammation. Frequent episodes of hypoglycemia during drinking are particularly strongly associated with the risk of developing insulin resistance and metabolic syndrome.
The second stereotype of “severe” CAI and the most common cause of active alcoholic hepatitis is regular heavy intoxication (drinking too much too often), or drinking >70-80 g of ethanol per day more than 3 times a week. . In patients who have stopped drinking alcohol, the progression of ALD is due to the progression of chronic hepatitis due to disruption of the intestinal biocenosis, intercurrent infections, as well as the influence of comorbid factors (obesity, chronic heart failure, cor pulmonale, drug and other toxic load). In those who continue to take alcohol, the main cause of decompensation of ALD and death is exacerbation of chronic hepatitis with decompensation of hepatic cellular function (acute-on-chronic liver failure). Another cause of death in cirrhosis is portal hypertension, which leads to massive bleeding from varicose veins.
Comorbidity in patients with ALD
CAI is a systemic disease that forms a stereotypical pathology of target organs on the basis of universal dose-dependent metabolic and immune-inflammatory disorders. However, target organ damage, which correlates with the severity of ALD, also has some organ specificity. Thus, for the functioning of “excitable” cells of the central nervous system, skeletal muscles and cardiomyocytes, already in the early stages of CAI, disruption of the conduction of impulses through the damaged outer cell membrane and in the cytosol (degradation of phospholipids, disruption of ion channels, changes in the number and structure of receptors) is of great importance, and also dysfunction of mitochondrial membranes, sarcoplasmic reticulum and sarcomeres. Clinically significant alcoholic myopathy with diffuse damage to the skeletal muscles develops in more than 50% of patients with cirrhosis. The formation of myopathy, like alcoholic cardiopathy, begins at the very beginning of CAI and remains completely reversible for a long time if alcohol is stopped. The development of persistent muscle weakness and irreversible atrophy occurs at approximately the level of total consumption of 20 g of ethanol per 1 kg of body weight. Alcoholic cardiopathy, like ALD, is also a “dose-dependent” pathology, despite the fact that the total risk of heart damage in CAI is higher in women and people with genetic defects in the activity of acetaldehyde dehydrogenase. In 30% of patients with CAI, diastolic cardiac dysfunction develops at an ethanol level of 5 g/kg body weight, and systolic dysfunction occurs in 13% of patients who took ethanol >9 g/kg body weight. According to autopsies, alcoholic cardiopathy develops in all those who died from CAI and has stereotypical pathological and anatomical signs: cardiomegaly, fat deposition under the epicardium, flabbiness and “clayey” appearance of the myocardium, thickening of the wall of the left ventricle, dilation of the cavities of the heart, thickening of the endocardium, atherosclerosis of the coronary arteries and branches of the aorta.
Microscopy typically reveals perivascular fibrosis, diffuse small-focal cardiosclerosis, myocardial lipofibrosis, alternating hypertrophy and atrophy of cardiomyocytes with their fatty degeneration and the deposition of lipofuscin in them (Fig. 8-11).
Clinically, diastolic cardiac dysfunction leads to arterial hypertension, and systolic dysfunction leads to the development of dilated cardiopathy and systolic heart failure, the frequency of which is steadily increasing in Russia. Both types of cardiopathy cause various cardiac arrhythmias and sudden death (Fig. 12). All histological manifestations and symptoms of alcoholic cardiopathy are potentiated by chronic cocaine use and heavy smoking.
CAI dose-dependently causes damage to the central nervous system: in those taking more than 60 g of ethanol per day, it increases the risk of hemorrhagic cerebral infarction by 2.18 times. Alcohol-induced dementia develops in 70% of patients, and cerebellar degeneration in 30% of patients with CAI with a total alcohol dose of >4 g/kg body weight. Clinically significant peripheral and autonomic neuropathy develops in 20% of women consuming >40 g/day and men consuming >60 g/day. Other specific CNS lesions closely associated with nutritional, electrolyte and vitamin imbalances include Korsakoff-Wernicke encephalopathy (vitamin B1), central pontine myelinolysis, and pellagra (nicotinamide). According to autopsy data, brain lesions in CAI are characterized by: fibrosis of the pia mater, pinpoint hemorrhages in the subcortex, caudate and lenticular nuclei, hypothalamus, calcifications in the choroid plexuses of the ventricles of the brain. The convolutions of the brain are smoothed, the furrows are widened, mainly in the frontal and temporal lobes. The walls of the arteries of the brain are sclerotic, there are foci of fibrinoid necrosis. It is characteristic that in the brain the consequences of CAI-induced apoptosis and impaired cellular regeneration are most pronounced - in the frontal and temporal cortex, in the cerebellum and hypothalamus, there is a depletion of cellular elements, a significant increase in the number of decaying neurons compared to the norm (Fig. 13, 14).
For “quiet” cells of the glands, intestines and others, as well as for the liver, metabolic, hormonal, immunological and inflammatory damage associated with CAI is more important. Considering the critical role of translocation of bacterial lipopolysaccharides from the intestine to the liver for the development and progression of ALD, it is necessary to actively identify and treat gastrointestinal pathology in patients with CAI. Gastrointestinal tract damage associated with CAI is formed under the direct toxic effects of ethanol and acetaldehyde, as well as due to systemic intoxication, electrolyte imbalance, and activation of the local neuroendocrine and immune systems. The combined influence of these factors reduces the density of intercellular contacts, increases the secretion of antibodies and cytokines on the surface of the epithelium - leads to high vulnerability of the mucous membrane, increases the amount of microflora and disrupts the microbial landscape. It has been proven that patients with CAI always develop bacterial overgrowth with an increase in the proportion of opportunistic gram-negative rods and displacement of indigenous bacterial flora (Fig. 15).
Alcohol-associated intestinal damage is characterized by a decrease in general (immunological, toxic and mechanical) tolerance of the mucous membrane. As already mentioned, this leads to the translocation of bacterial lipopolysaccharides into the liver, which plays an activating role in the development of inflammation in the liver parenchyma, fibrogenesis, as well as in the formation of a systemic humoral and cellular inflammatory response. In this case, tissue damage occurs not only locally, as in the liver, but also due to systemic immune disorders and through CD4+/CD8+ lymphocytes sensitized in the intestine. Immunity disorders associated with CAI reduce the body's resistance to infections, which plays a key role in the development of respiratory diseases. According to pathological and anatomical studies, all those who died with CAI had chronic bronchitis with pronounced perivascular and peribronchial fibrosis (Fig. 16, 17). Microscopic examination revealed a higher than normal frequency of multiple bilateral pulmonary microatelectasis, which is one of the most important reasons for the high incidence of severe lobar or focal confluent multifocal pneumonia in patients with CAI.
All those who died from CAI had pronounced changes in the pancreas - compaction and fibrosis of the stroma with a violation of its lobular structure and the presence of petrification in 90% of cases. On microscopy, finely focal periductal sclerosis with large fields of parenchymal sclerosis and atrophy of acinar cells was present in all cases. In 69% of cases, the lobular ducts were dilated and contained protein precipitates; in 28% of cases, lymphohistiocytic infiltration was noted in the parenchyma. Thus, in patients with CAI, even at the stage of compensated alcoholic polyvisceropathy, there was a clear stereotypical lesion of almost all internal organs. Its distinctive features are fatty degeneration of internal organs, primarily the liver and heart; fibrosis and sclerosis in the stroma of the heart, liver, lungs and pancreas, death of neurons in the brain, hyalinosis and severe sclerosis of the arteries, as well as systemic microangiopathy with increased vascular permeability of the microvasculature, reflecting both intoxication and a high level of systemic inflammation.
Risk factors and progression of ALD
Drinking risky amounts of alcohol, according to epidemiological studies, leads to the development of ALD only in 6-41% of patients and mainly in frequent drinkers. With the same CAI scenario, forms of ALD that differ in severity and progression potential develop. This individual variability is determined by a combination of genetic factors, environmental influences and the patient’s comorbid status (Table 2).
Women are 2 times more predisposed to ALD: they are prone to developing more severe lesions under the influence of low doses of alcohol and a shorter duration of CAI. This is explained by slower estrogen-dependent hepatic and extrahepatic metabolism of alcohol, higher adipose tissue content, less resistance to oxidative stress and a certain activating effect of estrogens on various parts of the innate immunity and inflammatory cascade in the liver parenchyma.
The course of ALD is significantly aggravated by obesity (especially visceral), which is also the cause of non-alcoholic fatty liver disease (NAFLD). The pathogenetic mechanisms common to ALD and NAFLD (induction of CYP 450 2E1, oxidative stress and lipid peroxidation, active production of proinflammatory cytokines and fibrogenesis factors by adipose tissue) increase the activity of hepatitis, promotes the early formation of cirrhosis and increases mortality from all forms of ALD. According to C. Hart et al. (2010), the combination of obesity and alcohol abuse exponentially increases the risk of death from liver disease compared with non-drinkers or people of normal weight. For those who drink more than 15 doses of ethanol per week with normal weight, the risk of death from any form of liver pathology is 3.16 times higher (95% confidence interval 1.28 to 7.8), for drinkers and those who are overweight - 7.01 ( 3.02 to 16.3), in drinking obese patients - 18.9 (6.84 to 52.4) times. In obese people and light drinkers (1-14 drinks per week), the relative risk of death was slightly lower - 5.3 (1.36 to 20.7) (Fig. 18).
Obesity actively potentiates the inflammatory cascade and especially fatally increases the risk of cirrhosis in women consuming more than 150 g of ethanol per week (Fig. 19). According to B. Liu et al., obesity increases the incidence of non-alcoholic cirrhosis by 17% and the incidence of alcoholic cirrhosis by 42%. It is characteristic that in general medical practice, metabolic obesity and overweight often prevent the timely diagnosis of alcoholic cirrhosis, which is empirically associated with underweight. In fact, fatty infiltration of the liver and other internal target organs: heart, brain and skeletal muscle during alcohol abuse is a highly specific and, initially, reversible marker of regular heavy alcohol consumption.
Contrary to the common perception of excess body weight, visceral obesity in patients with ALD does not at all indicate a nutritious and high-calorie diet. On the contrary, as the violations of hepatic cellular function deepen in patients, profound disturbances in nutrient status increase, primarily in relation to essential protein (methionine, cysteine) and micronutrients (manganese, lithium, selenium, zinc), essential phospholipids (EPL) (polyunsaturated fatty acids ) and vitamins (thiamine, folic acid, carotenes, tocopherol, riboflavin, nicotinamide, vitamin K). Assimilation disorders, characteristic of liver failure, are aggravated by the addition of malabsorption due to insufficiency of external and endocrine pancreatic secretion, biliary insufficiency and excessive bacterial growth in the gastrointestinal tract. Malabsorption predominantly impairs the absorption of fats and manifests a deficiency of fat-soluble vitamins and essential lipids, and also accelerates osteoporosis. Violation of nutritional status, like obesity, significantly reduces tolerance to the toxic effects of alcohol and potentiates pathological metabolic immune-inflammatory processes caused by CAI, and therefore requires active identification and correction.
Diagnosis and treatment of alcoholic polyvisceropathy
Timely treatment of alcoholic polyvisceropathy is significantly difficult, primarily because 90% of patients with early forms of alcoholic polyvisceropathy for many years do not develop nosologically defined lesions of internal organs that can be correlated with alcohol abuse. In a therapeutic clinic, such patients are usually diagnosed with exacerbation of cardiovascular diseases, more often - arterial hypertension or chronic obstructive pulmonary disease, less often - chronic pancreatitis or exacerbation of peptic ulcer disease. The main reasons for hospitalization of patients are acute pancreatitis, complicated peptic ulcer, “alcohol injury” and pneumonia. In Russia, as in other large countries with a similar social structure and standard of living of the urban population, for example in Brazil, patients with exacerbation of alcoholic polyvisceropathy account for up to 80% of urgent hospitalizations of non-surgical patients in the intensive care unit of a multidisciplinary hospital. In clinical practice, such patients are usually empirically diagnosed with CAI, but close attention to their alcohol history occurs almost exclusively when emergency surgical interventions are necessary - to predict withdrawal syndrome in the early postoperative period. In fact, in these patients, the “preclinical” stage should be considered as the first stage of alcoholic polyvisceropathy, since specific multi-organ lesions of the internal organs not only already exist, but also often cause death.
To identify the fact and nature of CAI, it is customary to use standardized tests CAGE, AUDIT, and to identify, in particular, its somatic equivalents, the “LeGo Grid” questionnaire (P.M. LeGo, 1976), standardized and modified for use in Russia. A combination of 7 or more signs indicates the presence of chronic alcoholic polyvisceropathy (Table 3). Application of the test in a study undertaken in 2005-2006. in one of the multidisciplinary hospitals in Moscow, made it possible to diagnose alcoholic polyvisceropathy in 44% of patients of various genders and ages hospitalized in the cardiology and therapeutic departments of the hospital.
To identify alcoholic polyvisceropathy, it is advisable to perform a minimum amount of research, which will allow us to establish the severity and indications for treatment (Table 4).
International and Russian clinical guidelines for the treatment of ALD strictly regulate the algorithms of action and the volume of drug therapy for potentially lethal forms of ALD: withdrawal syndrome, severe acute alcoholic hepatitis and decompensated cirrhosis. Among the pharmacological interventions that are the focus of these clinical recommendations are:
. benzodiazepines to treat withdrawal symptoms;
. terlipressin for the treatment and prevention of hepatorenal syndrome and bleeding from esophageal varices;
. prednisolone in the treatment of histologically verified severe acute hepatitis;
. N-acetylcysteine ​​as an antioxidant;
. refusal of empirical antibiotics;
. parenteral nutrition.
At the same time, almost all aspects of long-term anti-inflammatory and antifibrotic treatment of metabolic disorders and pathology of internal organs that are specific but comorbid for ALD remain outside the scope of clinical recommendations. Active influence on these pathogenetic mechanisms, without a doubt, could significantly improve the prognosis: slow down the progression of ALD and multiple organ failure, reduce mortality and improve the quality of life of patients. One of the attempts to use new molecular technologies for anti-inflammatory effects was the use, however, in an experiment of IL-6 and IL-22 in acute alcoholic hepatitis. For the purpose of antifibrotic effects, an attempt was made to use pentoxifylline as an antagonist of TNFα, a mediator associated with CAI liver damage and fibrosis. Pentoxifylline therapy was successful against markers of inflammation and fibrosis, but resulted in increased mortality in patients with severe alcoholic hepatitis due to an increased incidence of infectious complications.
In general, the treatment of stable forms of ALD with relatively preserved hepatic cellular function in practice is classified as symptomatic therapy, should be carried out in outpatient practice and therefore is in the scope of activity not so much of a gastroenterologist as of a general practitioner, family doctor or local therapist. The priorities in this direction should be the treatment of obesity and insulin resistance, correction of other metabolic disorders (hypoproteinemia, dyslipidemia, osteoporosis, deficiency of macro- and micronutrients), excessive bacterial growth in the intestine, aspects of adverse drug interactions during polypharmacotherapy and all resources of anti-inflammatory treatment, including hepatoprotectors.
In this class of drugs, the use of EPL as anti-inflammatory and antifibrotic agents is promising (taking into account extensive clinical experience and expert approval). In recent years, a number of controlled clinical studies have shown that treatment of EPL in ALD leads to an improvement in the laboratory profile and increases tolerance to CAI, and has a direct antifibrotic effect. The experiment showed that this anti-inflammatory and antifibrotic effect is realized through a dose-dependent decrease in lipid peroxidation caused by oxidative stress, as well as a decrease in TGF-α dependent activation of stellate cells. According to a meta-analysis, the effectiveness of EPL in ALD is 83.5%.
EPLs are especially effective against fatty diseases of both alcoholic and non-alcoholic nature, since through the polyunsaturated fatty acids they contain at the molecular level they directly activate the oxidation of free fatty acids in cell peroxisomes. In addition to hepatoprotective activity, EPL therapy significantly improves the lipid profile (reduces LDL and triglyceride titers), and also normalizes the structure and functional state of other tissues with a high content of phospholipids: brain, blood cells, gastric mucosa.
Some EPL drugs have advantages in the treatment of alcoholic steatohepatitis and cirrhosis, since they contribute to the correction of the deficiency of essential amino acids and protein characteristic of ALD. Methionine and EPL enhance each other's effects, improve the functional state of liver cells and have a hepatoprotective effect.
Thus, while a detailed deciphering of the molecular mechanisms of ALD has not yet led to the creation of new effective treatment methods, the arsenal of an experienced doctor already has reliable drugs for planned long-term therapy of alcoholic polyvisceropathy.

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38. National Clinical Guideline Center for Acute and Chronic Conditions. Alcohol-use disorders. Diagnosis and clinical management of alcohol-related physical complications. London (UK): National Institute for Health and Clinical Excellence (NICE); 2010 Jun. 30 p. http://www.guideline.gov.
39. O'Shea R.S., Dasarathy S., McCullough A.J., Practice Guideline Committee of the American Association for the Study of Liver. Alcoholic liver disease // Hepatology. 2010 Jan. Vol. 51 (1), pp. 307-328.
40. Mathurin P., Hadengue A., Bataller R. et al. EASL Clinical Practical Guidelines: Management of Alcoholic Liver Disease // J Hepatol. 2012. Vol. 57. R. 399-420.
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Key messages from the updated clinical guidelines of the European Association for the Study of the Liver

1. Standard dose of alcohol The one recommended by WHO and containing 10 grams of pure alcohol was chosen. Heavy episodic use is equivalent to taking more than 60 grams of pure alcohol at one time. Excessive alcohol consumption - taking 4 or more standard doses within two hours for women, 5 or more for men.

2. Alcohol is a recognized carcinogen, its consumption is associated with an increased risk of developing several types of cancer, starting with doses exceeding the standard dose of alcohol per day.

3. There is convincing evidence that drinking alcohol in large quantities increases the risk

• cardiomyopathy,
• arterial hypertension,
• atrial arrhythmias and
• hemorrhagic stroke.

4. Alcohol is a risk factor for cirrhosis, however, it is unclear whether there is an intake threshold at which risk arises.

5. Moderate drinkers reduce the risk of coronary artery disease.

• Instead of “alcoholic”, “alcohol addiction” it is proposed to use the term “ alcohol use disorder"(RSUA);
• The AUDIT or AUDIT-C should be used to screen for alcohol use disorders (AUD);
• Patients with MSAD should be screened for mental disorders and other addictions;
• Benzodiazepines should be used to treat alcohol withdrawal syndrome, but not for more than 10-14 days due to the potential for abuse and/or encephalopathy;
• Pharmacotherapy should be considered in patients with RSAD and alcohol-related liver disease;
• liver biopsy is required in cases of diagnostic uncertainty, when it is necessary to clarify the stage of fibrosis;
• Screening of patients with RSAD should include liver tests and determination of the degree of liver fibrosis;
• Alcohol withdrawal is suggested to be monitored by measuring ethyl glucuronide (EtG) in urine or hair.

Alcoholic hepatitis (AH)

The recent onset of jaundice with excessive alcohol consumption should prompt clinicians to suspect alcoholic hepatitis (AH).

In the absence of active infection, corticosteroids (prednisolone 40 mg/day or methylprednisolone 32 mg/day) should be considered in patients with severe hypertension to reduce short-term mortality.

However, corticosteroids do not affect mid- and long-term survival. N-acetylcysteine ​​(intravenous over five days) can be combined with corticosteroids in patients with severe hypertension. Daily oral intake of ≥ 35–40 kcal/kg body weight and 1.2–1.5 g/kg protein is required as a first-line intervention.

Routine screening for infections should be performed prior to initiation, during treatment with corticosteroids, and during the observation period.

It is necessary to identify early (on the seventh day) lack of response to corticosteroid therapy and adhere to strict rules for stopping therapy.

Fibrosis and cirrhosis of the liver caused by alcohol abuse

Patients with cirrhosis caused by excessive alcohol consumption should be advised to completely abstain from alcohol to reduce the risk of complications and mortality.

Changes in the structure of the liver under the influence of ethanol with persistent impairment of organ function - alcoholic liver disease (ALD): ICD 10 - K70. Clinical manifestations of the pathology are typical for diseases of the digestive system: lack of appetite, nausea, aching pain under the ribs on the right, yellowness of the skin and sclera, dyspepsia. The structure of the liver progressively degenerates with the development of hepatic encephalopathy and the outcome of cirrhosis. In order to correctly establish a diagnosis, a complete clinical and laboratory examination of the patient is necessary, including organ biopsy. Treatment is based on stopping contact with ethanol, taking a complex of medications, including hepatoprotectors, and sometimes transplantation is required.

In almost all developed countries, wine drinking is at a fairly serious level: on average, up to 10 liters of pure alcohol per year per person. Russia is in 4th place in terms of alcoholism. In the world, about 20 million are dependent on ethanol, the share of ABP reaches 40%. It should be taken into account that cirrhosis makes up only 10% of liver pathology; for its development it takes at least 10 years of alcohol abuse.

Development factors

The liver is the main organ that metabolizes ethanol (85%). The rest comes from the stomach. Two enzymes are involved in the utilization of alcohol: alcohol dehydrogenase and acetate dehydrogenase. Their ability to break down ethanol is inherited. The more a person drinks, the more actively enzymes work, and a catabolic accumulation of toxic substances occurs in the liver and stomach. They begin to destroy hepatocytes, which are immediately replaced by connective tissue. This is how cirrhosis with liver hypoxia is formed. The following points aggravate the situation:

• Gender factor: women get sick faster and suffer pathological changes very hard.
• Genetic inability to produce enzymes that destroy alcohol, which leads to the destruction of hepatocytes even with small doses of alcohol.
• Impaired metabolism (diabetes mellitus, extra pounds).
• Viral hepatitis and other liver infections.

The development of pathology occurs against the background of excessive use of ethanol.

Forms of pathology

Structural changes in liver hepatopathy are usually classified.

There are:

• Fatty hepatosis is the displacement of the cytoplasm of hepatocytes by a lipid vacuole. Develops in 100% of cases and is asymptomatic.
• Lipid hepatitis is a type of disease associated with inflammation of hepatocytes with parallel fat deposition. It always has a subacute course and is characterized by the appearance in the liver cells of giant mitochondria - the energy stations of cells trying to digest fat. This is, in fact, the debut of fatty liver degeneration.
• Hepatofibrosis is the replacement of liver cells with connective tissue elements within the organ. The mitochondria of hepatocytes cannot cope with the excessive load, and the cell dies and is immediately replaced by connective tissue. At this stage, the liver capillaries are involved in the process, they are destroyed, internal bleeding occurs, varicose veins of the hepatic vessels are formed, and the coagulation process begins with the development of spontaneous peritonitis. This is a bad prognostic sign.
• Cirrhosis is wrinkling of liver tissue due to the almost complete replacement of hepatocytes with connective tissue, disrupting the normal functioning of the organ and changing its size. Portal hypertension develops.
• Liver failure (LF), occurring acutely or chronically and leading to complete depletion of organ function.

Pathogenesis

The mechanism of development of alcoholic disease is gradual. The liver undergoes a number of general, sequential transformations:

• Utilization of methanol by liver enzymes through the oxidation of primary acetaldehyde to acetate. This causes oxidative stress to the organ and triggers liver destruction. All biochemical transformations occur at the microsomal level.
• The destruction of liver cells contributes to the disruption of mitochondrial (energy) functions, blocking the DNA of hepatocytes and the impossibility of their reproduction. The remaining liver cells interact with the proteins of the dermis. Hepatocollagen complexes are formed, which impair liver immunity. The constant intake of alcohol in the body provokes the formation of free radicals, which selectively associate with hepatocytes, destroying them, while leaving collagen intact. Thus, liver tissue is pathomorphologically and pathoanatomically replaced by fibrosis.
• The immune system produces toxic lymphocytes (CD4 and CD8), which accompany the acute version of alcoholic hepatitis. They inhibit immunocompetent cells and indirectly encourage intoxication, which manifests itself in jaundice of the skin, weight loss, fever, and dyspepsia.

Symptoms

The first symptoms appear after years of alcohol abuse; latent steatosis provides this opportunity. But as it develops, like everything else in alcoholic illness, it is subject to temporary stages:

• The latent initial stage of the disease is replaced by inflammation (hepatitis). Characteristic symptoms during this period are: dull pain in the right hypochondrium, jaundice of the skin, intoxication. Sometimes all this is so strongly expressed, it develops so rapidly that it instantly affects the kidneys, heart, hematopoiesis, and central nervous system, leading to death. Doctors do not have time to provide appropriate assistance. If the acute phase becomes chronic, then if you give up alcohol, the process can be stopped.
• Cirrhosis is the final stage of ALD, manifested by a variety of syndromes associated with damage to internal organs and tissues; the changes are not reversible. Symptoms of chronic intoxication are primarily visualized by red palms and the appearance of many superficially located varicose vessels. This is how coagulation disorders manifest in the blood clotting system and changes in the capillary wall under the influence of toxins.

Patients' nails become deformed, fingers resemble drumsticks, women notice enlarged mammary glands, and men's testicles become smaller. The body undergoes systemic changes under the influence of alcohol toxins: muscles lose their tone, myalgia occurs, the volume of muscle mass is lost, nerve endings and trunks are deformed, and the coordination connection with the brain and spinal cord is disrupted. Shortness of breath, tachycardia increases, movements are limited (the joints are fibrously changed). The outcome is unfavorable. With cirrhosis, life expectancy is limited to five years.

Diagnostics

Making a clinical diagnosis of alcoholic illness requires scrupulousness and a complete instrumental and laboratory examination of the patient. The algorithm of actions includes:

• Collecting anamnesis (time of alcohol abuse, heredity is important).
• Physical examination (multi-colored symptoms of skin changes, organ boundaries) and assessment of the psycho-emotional state to exclude encephalopathy.
• CBC (blood flow screening to diagnose hypoxia, inflammation, platelet count).
• Blood biochemistry (monitoring the function of internal organs, water and electrolyte metabolism).
• Fibrosis markers (prothrombin (P), glutamyl transpeptidase (G) - liver tissue enzyme, A1 (A) - alipoprotein that prevents vasoconstriction). When PGA is above 7, complications are predicted in 90% of cases.
• Serum markers: hyaluronic acid, collagen and procollagen, matrix enzymes. Their presence indicates fibrosis.
• Coagulogram – screening of the blood clotting system.
• Lipid spectrum – increased triglycerides.
• Liver tumor marker (alpha-fetoprotein) – presence confirms cancer.
• Markers of viral hepatitis.
• Biochemical testers for the duration of alcohol abuse (Ig A, AST, ALT, transferrin.
• OAM for assessing kidney potential.
• Coprogram – screening of the digestive system.
• Ultrasound of the liver and spleen.
• EGD is performed to visualize varicose veins of the upper digestive system.
• Liver biopsy if malignancy is suspected or it is impossible to establish an accurate diagnosis in any other way. An alternative is elastography, which determines the degree of fibrosis using a hardware technique for compressing the liver with ultrasound.
• CT, MSCT, MRI.
• Contrast cholangiography - identifies the cause of the obstruction of bile outflow.

Treatment

ALD therapy has two goals: to stop the progression of the pathology and to prevent the development of complications.

Non-drug therapy

The basis is abstinence from alcohol. In this case, steatosis disappears spontaneously after a month. Prescribing a diet speeds up the process. Protein is included in the diet in large quantities (dysproteinemia of alcoholics) and calorie content is calculated. Vitamins and microelements enter the body with food (replacement with multivitamin complexes is possible). For anorexia - feeding through a tube.

Medications

Drug treatment involves a set of measures:

• Detoxification: solutions of Essentiale and Glucose, Pyrodoxin, Thiamine, Cocarboxylase, Nootropil, Hemodez. The course is five days, intravenously.
• Hormones (in the absence of bleeding and for health reasons): Metipred, Prednisolone, Kenacort, Urbazon, Celeston in a monthly course of 32 mg per day.
• Uro acids that stabilize hepatocyte membranes and improve liver enzyme parameters: Ursosan, Ursofalk, Exchol according to an individual scheme.
• Essential phospholipids are drugs that restore the hepatocyte membrane, exhibit antioxidant properties, have antifibrotic and antidepressant activity: Essentiale, Phosphonciale, Antraliv, intravenously, infusion.
• The Ademetionine group disinfects toxins, participates in regeneration, and provides their protection from ethanol: Heptor, Heptralite.
• Tissue protease blockers - prevent scarring: Ingiprol, Aprotinin, Antagozan.
• Vitamins A, E, C, B, PP.
• ACE inhibitors - prevent fibrosis: Capozide, Enzix, Accuside.
• Hepatoprotectors: Karsil, Gepabene, Silimar.

Physiotherapy

For ALD, it is reduced to reflexology, electrophoresis of drugs, massage and exercise therapy.

Surgery

It is methodologically justified and is used for complications of ALD. In case of cirrhosis, organ transplantation is indicated. You must first avoid alcohol for six months. The operation prolongs life by 5 years in 50% of cases.

Herbal Recipes

Traditional medicine recommends hawthorn, knotweed, oats, and nettle in the form of decoctions. The following recipe is popular: 100 g of honey per half liter of water. Boil on the stove to 1/3 of the original volume. Pour this hot solution into a mixture of herbs (5 g each) of chamomile, tansy, yarrow, dandelion, calamus. Infuse, filter, drink a third of a glass per day.

Complications

It is necessary to note the risk of bleeding, chronic renal failure, bacteritonitis, encephalopathy of hepatic origin, transformation of fibrosis into carcinoma.

Prognosis and prevention

The patient's future depends on the stage of the process and the severity of ALD. The prognosis for steatosis is certainly favorable. Everything returns to normal within a month when contact with ethanol is stopped. Women are at risk.

Prevention

Taking more than 50 g of pure alcohol per day by men and more than 15 g by women is a sure way to cirrhosis (1 ml of any alcohol contains 0.8 g of ethanol). Apart from giving up alcohol, there are no other recommendations. A dose of 40 g for men and 20 g for women per day is sufficient for the development of ALD.

Scientists at the University of Exeter have discovered a surprising fact: alcohol also has a positive effect on the body. It turns out that it can stimulate memory and increase learning ability. In moderate doses, of course. If you have received new, valuable information that you urgently need to remember, a sip of quality alcohol will help with this. The drinker will retain the data in memory and, most importantly, will help to accurately reproduce it. But if you go too far with the dose, the opposite reaction will occur: no matter how much you remember later, nothing will happen. Reviews about the opening are only good. Photo verified.

Version: MedElement Disease Directory

general information

Short description

Classification

Most clinicians distinguish between acute and chronic alcoholic hepatitis.

2. Acute alcoholic hepatitis (acute alcoholic liver necrosis):
- in combination with chronic alcoholic hepatopathy;
— developed in an intact liver;
- with intrahepatic cholestasis;
- mild (anicteric) form;
- moderate form;
- severe form.

Etiology and pathogenesis

1. Acute alcoholic hepatitis. Histological manifestations:
1.1 Structural changes in the liver required for alcoholic hepatitis:
- perivenular damage to hepatocytes;
— balloon dystrophy and necrosis;
— presence of Mallory bodies (alcoholic hyaline);
- leukocyte infiltration;
- pericellular fibrosis.
1.2 Symptoms that are not necessary for the diagnosis of alcoholic hepatitis:
- fatty liver;
— identification of giant mitochondria, acidophilic bodies, oxyphilic hepatocytes;
— fibrosis of the hepatic veins;
- proliferation of bile ducts;
- cholestasis.

Perivenular damage to hepatocytes
Acute alcoholic hepatitis is characterized by perivenular damage to hepatocytes or the third zone (microcirculatory periphery) of Rappoport's hepatic acini. During the metabolism of alcohol, a more noticeable decrease in oxygen tension is observed in comparison with the norm in the direction from the hepatic artery and portal vein to the hepatic vein. Perivenular hypoxia promotes the development of hepatocellular necrosis, which is found mainly in the center of the hepatic hexagonal lobes.

Inflammatory infiltration of polynuclear leukocytes with a small admixture of lymphocytes is determined inside the lobule and in the portal tracts. Inside the lobule, leukocytes are detected in foci of hepatocyte necrosis and around cells that contain alcoholic hyaline, which is associated with the leukotoxic effect of alcoholic hyaline. When the disease subsides, alcoholic hyaline is less common.

Pericellular fibrosis is an important feature of alcoholic hepatitis, and its prevalence is a key indicator in predicting the disease. Alcohol and its metabolites (especially acetaldehyde) can have a direct fibrogenic effect. Fibrous tissue is deposited along the sinusoids and around hepatocytes in the early stages of alcoholic hepatitis. Ito cells, fibroblasts, myofibroblasts and hepatocytes synthesize various types of collagen and non-collagenous proteins.

2. Chronic alcoholic hepatitis:

2.2 Chronic active hepatitis: histological picture of alcoholic hepatitis in combination with active fibrogenesis. Along with significant fibrosis, sclerosing hyaline necrosis is noted in the third zone of the lobule. After 3-5 months of abstinence, morphological changes resemble the picture of chronic aggressive non-alcoholic hepatitis.

In chronic alcoholic hepatitis, progression of the process in some cases is observed even after stopping the use of alcoholic beverages as a result of the addition of an autoimmune destructive reaction.

Epidemiology

Sign of prevalence: Common

Risk factors and groups

Clinical picture

Clinical diagnostic criteria

Symptoms, course

Anamnesis
Diagnosis of alcoholic hepatitis is associated with certain difficulties, since it is not always possible to obtain sufficiently complete information about the patient.

Alcohol abuse(detected by the presence of one or two signs):

Types of clinical course of alcoholic hepatitis:

Source http://diseases.medelement.com/disease/%D0%B0%D0%BB%D0%BA%D0%BE%D0%B3%D0%BE%D0%BB%D1%8C%D0%BD% D1%8B%D0%B9-%D0%B3%D0%B5%D0%BF%D0%B0%D1%82%D0%B8%D1%82-k70-1/4785

Alcoholic hepatitis is an acute liver disease resulting from the destructive effect of alcohol breakdown products on hepatocytes. This pathology develops in both men and women, although it occurs several times more often in men. With a long course, it turns into more severe pathologies: steatosis, fibrosis, steatohepatitis or cirrhosis of the liver. The disease may occur in acute or chronic form.

Characteristics of the disease

Hepatotoxic doses of alcohol differ for males and females. For men – 40-80 g/day in terms of pure ethanol. This amount contains 100-200 ml of vodka, 0.5 liters of wine, 1.5 liters of beer. For the weaker sex, this dose is 2 times less.

How it manifests itself

When examining the patient, you can see bright signs pathognomonic for this pathology. For example, these are bright telangiectasia, Dupuytren's contracture, hypertrophy of the parotid glands, a decrease in the volume and strength of the muscles of the upper extremities, and easy bruising. As well as minor hemorrhages on the mucous membranes, gastrointestinal bleeding, peripheral neuropathy.

Alcoholic hepatitis has two forms: persistent and progressive. The persistent form is characterized by a stable course. With complete abstinence, hepatocytes tend to recover.

With a progressive form, more severe pathologies develop. Finely focal liver necrosis occurs, progressing to cirrhosis. Symptoms will be more specific.

The disease begins with diarrhea and vomiting. Later, fever, yellowness of the skin and sclera, and pain in the right hypochondrium develop.

Laboratory tests show bilirubinemia and immunoglobulinemia A. An increase in gammaglutamyl transpeptidase and transaminases is observed.

The clinical course of the disease depends on risk factors, which can be divided into two groups: external and internal.

External factors include the type of alcoholic drink, duration of use and dose. In addition, the severity of symptoms is influenced by gender (it is known that symptoms of alcoholic hepatitis appear earlier in women than in men), nationality, and concomitant diseases.

Internal factors include a person’s genetic predisposition to inflammatory liver diseases. There is also a certain pattern between the daily dose and the form of alcoholic liver disease. It is known that the higher the dose of alcohol consumed daily, the more pronounced the degenerative changes.

How to treat

To begin with, the patient must stop drinking alcohol and follow a protein diet with a daily calorie content of an average of 2000 kcal. Without this prerequisite, effective therapy can be forgotten.

Basic therapy includes essential phospholipids or hepatoprotectors - Essentiale Forte, Gepagard Active. Detoxification therapy is carried out - the most accessible remedy is saline solution. Vitamin therapy is carried out: thiamine, vitamin A, vitamin D are administered intramuscularly and folic acid and zinc are administered orally.

In severe cases, they resort to liver transplantation, but this method of treatment is not available to everyone, however, after a liver transplant it is noted that patients are much less likely to return to alcohol.

Sometimes surgeons resort to removing the affected part of the liver. This occurs when drug therapy is ineffective. Before the operation, careful preparation is required, and the volume of intervention is determined individually and depends on the severity of liver damage, concomitant diseases and age.

The first signs develop quite late, so it is not always possible to diagnose the disease on time.

Many studies show that women develop inflammation in the liver faster due to alcohol abuse. This is explained by the different activity of the alcohol dehydrogenase enzyme in men and women.

It is known that in women the activity of this enzyme is lower. This affects the rate of breakdown of ethanol in the female body. Therefore, the first signs in women appear much earlier.

Thus, asthenovegetative syndrome manifests itself first. Next comes fever. Icterus of the skin and mucous membranes gives way to icterus.

Symptoms specific to men include gynecomastia - enlargement of the mammary glands.

In addition, asthenovegetative syndrome is added: loss of appetite (due to the high calorie content of alcohol), general fatigue and weakness. As in women, in men obesity is an additional risk factor for the development of degenerative changes.

1. Refusal to take alcohol and alcohol-containing substances.
2. Patients who abuse alcohol must undergo an examination to promptly suspect and diagnose alcoholic hepatitis.
3. Increased protein content in food – 1g per kg of body weight.
4. Taking vitamins A, D, folic acid, thiamine, zinc.
5. Drug therapy prescribed by a doctor.
6. When diagnosed with alcoholic liver disease, careful monitoring of kidney function is necessary, as well as examination to identify infectious diseases, since there is a high probability of development against the background of the underlying disease.

Having learned about the diagnosis of Alcoholic Hepatitis, patients are concerned about how long they will live with it. The prognosis is very variable and depends on many factors. Thus, the stage of hepatitis is of great importance, whether the patient has given up alcohol, is following a diet, and whether complications are observed against the background of the underlying disease.


On average, if the patient completely abstains from alcohol, and the severity of the damage is moderate or mild, he can live quite a long time. Accordingly, the chances decrease if the degree of liver damage is severe and the patient does not limit alcohol consumption. In this case, the count is not in years and months, but in weeks.

Chronic form

Chronic hepatitis manifests itself in moderate expression of clinical and laboratory symptoms; it can go unnoticed for a long time, so it cannot always be noticed immediately. The AST and ALT indicators gradually increase, and the ratio of AST to ALT will be positive. Moderate cholestasis syndrome.

• bursting pain due to tension of the Glissonian capsule due to edema and infiltration of the liver,
• yellowness of the skin and sclera due to the death of hepatocytes and the release of bilirubin pigment;
• discoloration of feces due to the binding of stercobilin;
• darkening of urine.

Acute form

Acute hepatitis progresses rapidly and occurs in the following forms:

• latent;
• cholestatic;
• fulminant;
• icteric.

The latent form does not have a specific clinic. General symptoms prevail: dyspeptic (nausea, vomiting, heartburn, diarrhea) and pain, which is characterized by bursting pain and a feeling of heaviness in the right hypochondrium.

The fulminant form is manifested by a sharp change in laboratory blood parameters, hemorrhagic and hepatorenal syndrome. This is the most severe form, as the mortality rate is high.

The icteric form is manifested by icterus of the skin and sclera, anorexia, dyspeptic disorders, and fever. The liver is enlarged and painful.

Blood analysis

Alcoholic hepatitis can be suspected already at the stage of obtaining the results of blood tests. With prolonged use of alcohol, a general blood test will change the ESR indicator towards its increase.

The number of reticulocytes increases, and hemoglobin, on the contrary, decreases. Slight thrombocytopenia is possible.

In a biochemical blood test, the results of liver tests pay attention. There is a significant increase in total bilirubin and a decrease in direct bilirubin.

There is an increase in the amount of AST, ALT, alkaline phosphatase, LDH and thymol test. If you analyze the lipid profile, you will notice that its indicators for alcoholic hepatitis are at the lower limit of normal.

A general urine test will show an alkaline environment (normal urine is slightly acidic). Urine will contain increased amounts of protein, leukocytes, epithelium and red blood cells.

Hair loss

Before answering how hepatitis affects hair loss, let's remember what functions the liver performs. First of all, it is a barrier and detoxification function. It takes upon itself the neutralization of toxins and damaging elements that enter the body.

With this disease, the cells of the liver tissue are destroyed, the organ is not able to cleanse the body in full. This affects the hormonal system, which is responsible for the production of hormones by the endocrine glands.

Destruction of the liver affects the sebaceous glands located at the hair follicle of each hair. Due to hypersecretion of the sebaceous glands, you have to wash your hair much more often. Hair becomes brittle and breaks and begins to fall out.

Prescribed drugs

In addition to the general recommendations that we described above, drug therapy is indicated for a patient diagnosed with alcoholic hepatitis. In severe cases, corticosteroids are prescribed: prednisolone or budesonide. The latter has fewer side effects.

After 7 days, the Lille index is calculated - an indicator demonstrating the effectiveness of steroid therapy. If the Lille index is less than 0.45, then the drug is continued for 28 days, followed by its discontinuation within 2 weeks.

If the index is more than 0.45, prednisolone is discontinued due to its ineffectiveness. It is important to screen for infection before prescribing prednisolone, since this drug suppresses the immune system, and the patient, along with eliminating the symptoms of alcoholic hepatitis, runs the risk of acquiring a secondary infection.

If the patient does not tolerate glucocorticosteroids, the drug pentoxifylline is prescribed. This is a second line drug. However, during experiments it was found that it has a better effect on relieving hepatorenal symptoms.

With moderate severity, the patient does not need steroid therapy. Its treatment begins with complete abstinence and adherence to a high-protein diet.

The following medications are prescribed:

1. Ademetionine. It reduces the level of AST and total bilirubin, and is relatively safe. In addition, this drug has an antidepressant effect and is prescribed in a double course.
2. Essential phospholipids – Evalar, Hepatrin. These drugs inhibit the accumulation of fat and have a lipolytic effect, that is, they break down fats in the liver. Neutralize toxins and promote the synthesis of new phospholipids.

For mild cases, it is enough to give up alcohol, follow a protein diet and take a course of hepatoprotectors.

Source http://zemed.ru/gepatit/alkogolnyj-simptomy-lechenie.html

For citation: Adzhigaitkanova S.K. Alcoholic hepatitis, basic principles of treatment // Breast cancer. 2008. No. 1. P. 15

“Alcoholic hepatitis” is a term adopted in the International Classification of Diseases (Tenth Revision of WHO, 1995) and in the standardization of nomenclature, diagnostic criteria and prognosis of diseases of the liver and biliary tract. It is used to refer to acute degenerative and inflammatory liver lesions caused by alcohol and which can, in a large number of cases, progress to cirrhosis. Alcoholic hepatitis is one of the main types of alcoholic liver disease; along with alcoholic fibrosis, it is considered a harbinger or the initial and obligatory stage of cirrhosis. This designation does not indicate the time duration of the process. It is advisable to separately consider acute and chronic alcoholic hepatitis.

Digestion is a set of processes that ensure the processing and transformation of food.

Source http://www.rmj.ru/articles/bolezni_organov_pishchevareniya/Alkogolynyy_gepatit_osnovnye_principy_lecheniya/

For quotation: Adzhigaitkanova S.K. Alcoholic hepatitis, basic principles of treatment // Breast cancer. 2008. No. 1. P. 15

“Alcoholic hepatitis” is a term adopted in the International Classification of Diseases (Tenth Revision of WHO, 1995) and in the standardization of nomenclature, diagnostic criteria and prognosis of diseases of the liver and biliary tract. It is used to refer to acute degenerative and inflammatory liver lesions caused by alcohol and which can, in a large number of cases, progress to cirrhosis. Alcoholic hepatitis is one of the main types of alcoholic liver disease; along with alcoholic fibrosis, it is considered a harbinger or the initial and obligatory stage of cirrhosis. This designation does not indicate the time duration of the process. It is advisable to separately consider acute and chronic alcoholic hepatitis.

When taken orally, about 90% of alcohol is metabolized in the liver to form acetaldehyde, a substance that affects liver cells - hepatocytes. Alcohol and its metabolites trigger a cascade of chemical reactions in the body, leading to hypoxia of hepatocytes and, ultimately, necrosis of liver cells.
Alcoholic hepatitis is a diffuse inflammatory process in the liver tissue, resulting from toxic damage to the liver by alcohol and its breakdown products. This is usually a chronic disease that develops 5-7 years after the start of regular alcohol consumption.
The severity of alcoholic hepatitis is directly related to the dose, quality of alcohol and duration of its use.
Alcoholic hepatitis manifests itself in two forms:
. Persistent form. A relatively stable form of the disease, the ability to reversible the inflammatory process is retained, subject to the cessation of alcoholism. With continued alcohol consumption, it can develop into a progressive form of alcoholic hepatitis.
. The progressive form (mild, moderate, severe active) is a small-focal necrotic liver lesion, the outcome of which is often liver cirrhosis. Accounts for 15-20% of cases of alcoholic hepatitis. With timely treatment of alcoholism, it is possible to stabilize inflammatory processes while maintaining residual effects.
In mild cases, alcoholic hepatitis is detected only through laboratory tests. There are no specific symptoms: periodically patients feel heaviness in the right hypochondrium, belching, mild nausea, and a feeling of fullness in the stomach. Chronic persistent hepatitis is histomorphologically manifested by pericellular and subsinusoidal fibrosis, Mallory bodies, balloon degeneration of hepatocytes. A similar picture without progression of fibrosis can persist for 5-10 years, even with moderate alcohol consumption.
The progressive form of alcoholic hepatitis may be accompanied by vomiting and diarrhea. Moderate and severe degrees of the course are manifested by jaundice, fever, bleeding, pain in the right hypochondrium, and death from liver failure is possible. Bilirubin, gammaglutamyl transpeptidase, immunoglobulin A, moderate thymol test and blood transaminase activity increase significantly.
Chronic active hepatitis has the above-described histomorphological picture of alcoholic hepatitis with the presence of active fibrosis and sclerosing hyaline necrosis to a greater or lesser extent. Abstain from alcohol for 3-6 months. leads to an improvement in the morphological picture of the type of chronic non-alcoholic hepatitis. Chronic active hepatitis in the presence of autoimmune destruction of the liver parenchyma is characterized by progression of the process with transition to cirrhosis. There are no direct morphological markers of the alcoholic etiology of liver diseases, but there are changes that are quite characteristic of the effects of ethanol on the liver. This is alcoholic hyaline (Mallory bodies), characteristic ultrastructural changes in hepatocytes and stellate reticuloepitheliocytes.
Characteristic ultrastructural changes in hepatocytes and stellate reticuloendotheliocytes reflect the toxic effects of ethanol on the body.
An important diagnostic value for chronic hepatitis (alcoholic, as well as any other etiology) is an ultrasound of the abdominal organs (liver, spleen and other organs), as well as to identify ascites and the size of the portal vein. Doppler ultrasound should be performed to exclude or establish the severity of portal hypertension. Traditionally, radionuclide hepatosplenoscintigraphy continues to be used for diagnostic purposes.
According to the course, acute and chronic alcoholic hepatitis are distinguished.
Acute alcoholic hepatitis (AAH) is an acute progressive degenerative-inflammatory liver disease. Clinically, OAS can be represented by four variants of its course: latent, icteric, cholestatic, fulminant. Long-term alcohol abuse leads to the formation of OAS in 60-70% of cases. In 4%, it relatively quickly transforms into alcoholic cirrhosis of the liver. The course and prognosis of acute alcoholic hepatitis depend on the severity of liver dysfunction. The most severe course of acute alcoholic hepatitis develops after alcoholic excesses against the background of formed alcoholic cirrhosis of the liver.
Clinical variants of acute alcoholic hepatitis usually develop after heavy drinking in patients with pre-existing liver cirrhosis, which causes aggregation of symptoms and significantly worsens the prognosis.
The latent variant, as its name suggests, does not provide an independent clinical picture and is diagnosed by an increase in transaminases in a patient who abuses alcohol. A liver biopsy is required to confirm the diagnosis.
The icteric variant is the most common. Patients experience severe weakness, anorexia, dull pain in the right hypochondrium, nausea, vomiting, diarrhea, weight loss, jaundice; the latter is not accompanied by skin itching. Approximately half of patients have remitting or persistent fever, often reaching febrile levels. The liver is enlarged in almost all cases, compacted, with a smooth surface (lumpy in cirrhosis), and painful. Detection of severe splenomegaly, ascites, telangiectasia, palmar erythema, and asterixis indicate the presence of background cirrhosis. Concomitant bacterial infections often develop: pneumonia, urinary infection, spontaneous bacterial peritonitis, septicemia. The latter, along with hepatorenal syndrome, often act as the direct cause of death.
The cholestatic variant is observed in 5-13% of cases and is accompanied by severe itching, jaundice, discoloration of stool, and dark urine. In the presence of fever and pain in the right hypochondrium, the clinical picture is difficult to distinguish from acute cholangitis. Cholestatic OAS is characterized by a protracted course.
Fulminant OAS is characterized by rapid progression of symptoms: jaundice, hemorrhagic syndrome, hepatic encephalopathy, and renal failure. Hepatic coma or hepatorenal syndrome usually leads to death.
Laboratory indicators. Neutrophilic leukocytosis is characteristic, reaching 20-40 thousand in 1 μl, an increase in ESR to 40-50 mm/h. Changes in red blood usually manifest as macrocytosis. Bilirubin increases mainly due to the direct fraction, reaching especially high levels in the cholestatic form. The activity of transaminases can increase both several times and tens of times, while the AST/ALT ratio exceeds 2. The activity of g-glutamyl-trans-peptidase increases many times, in the cholestatic form, together with alkaline phosphatase. IgA concentrations are usually elevated. In the presence of cirrhosis and severe OAS, biochemical signs of liver failure increase: an increase in prothrombin time (decreased prothrombin index), a decrease in serum albumin concentration, hyperammonemia. At the advanced stage of OAS, as a rule, there are contraindications to liver puncture biopsy. If the latter is nevertheless performed, then histological examination visualizes hepatocytes in a state of ballooning and fatty degeneration. Sometimes you can detect Mallory bodies, which, when stained with hematoxylin-eosin, are purple-red cytoplasmic inclusions consisting of condensed intermediate microfilaments of the cytoskeleton. There is more or less pronounced fibrosis with a perisinusoidal arrangement of collagen fibers. The typical sign is massive lobular infiltration with a predominance of polymorphonuclear leukocytes and areas of focal necrosis. Intrahepatic cholestasis is expressed to varying degrees.
Chronic alcoholic hepatitis. Clinical manifestations are the same as with ASP: a moderate increase in transaminase activity with a characteristic predominance of AST over ALT; in some cases, a moderate increase in indicators of cholestasis syndrome is possible. There are no signs of portal hypertension. The diagnosis is verified morphologically - characteristic histological changes corresponding to inflammation in the absence of signs of cirrhotic transformation.
Diagnosis of alcoholic liver damage and, in particular, alcoholic hepatitis is somewhat difficult. It is not always possible to obtain sufficiently complete information about the patient. Therefore, the doctor must know what is included in the concepts of “alcohol dependence” and “alcohol abuse.” The criteria for alcohol dependence are:
. the patient’s consumption of alcoholic beverages in large quantities and a constant desire to drink them;
. spending most of the time purchasing alcohol and drinking it;
. drinking alcohol in life-threatening situations or when it violates the patient's obligations to society;
. alcohol consumption, accompanied by a decrease or cessation of the patient’s social and professional activity;
. continued drinking alcohol, despite the worsening of the patient’s psychological and physical problems;
. increasing the amount of alcohol consumed to achieve the desired effect; the appearance of withdrawal symptoms;
. the need to drink alcohol to reduce withdrawal symptoms.
Alcohol dependence is diagnosed based on three of the above signs. Alcohol abuse is detected when one or two of the following signs are present:
. alcohol consumption, despite the patient’s increasing social, psychological and professional problems;
. repeated use of alcohol in life-threatening situations.
Treatment
Complex treatment of alcoholic hepatitis includes: elimination of the etiological factor, high-energy diet high in protein, drug treatment, surgical treatment. Treatment of any form of alcoholic hepatitis involves stopping drinking alcohol. However, it should be taken into account that no more than one third of patients actually completely give up alcohol after reporting the diagnosis; Approximately the same number significantly reduce the amount of alcohol they drink, while about 30% completely ignore the doctor’s recommendations. The last category is mainly represented by patients with alcoholism, who require the joint work of a hepatologist and a narcologist. Their unfavorable prognosis is determined by the inability to convince the patient of the need for abstinence due to alcohol addiction, on the one hand, and the presence of contraindications to the prescription recommended by a narcologist. neuroleptics due to liver failure, on the other. When abstaining from alcohol, jaundice, ascites and encephalopathy may disappear, but if the patient continues to drink alcohol and eat poorly, alcoholic hepatitis may recur. Sometimes these relapses end in death, but more often the symptoms disappear after a few weeks or months.
Endogenous depletion, caused by a decrease in glycogen reserves in the liver, is aggravated by exogenous depletion of patients who replenish the energy deficit with “empty” alcohol calories in conditions of increased need for nutrients, vitamins and microelements. A study carried out in the USA revealed some degree of nutritional deficiency in almost every patient with alcoholic hepatitis, while the severity of liver damage correlated with the severity of trophological deficiency. It should be noted that the average alcohol consumption in the study group was 228 g/day. (almost 50% of the energy received came from alcohol). Therefore, adequate nutritional intake is an important component of treatment.
The energy value of the diet should be at least 2000 calories per day, with a protein content of 1 g per 1 kg of body weight and a sufficient amount of vitamins (especially group B and folic acid, the deficiency of which is most often observed in alcoholics). For anorexia, enteral tube or parenteral nutrition is used. In the large group of patients with OAS mentioned above, a correlation of caloric intake with survival was demonstrated. Among patients who voluntarily took more than 3000 kcal per day, there were practically no deaths, while in the subgroup who consumed less than 1000 kcal/day, they amounted to more than 80%.
The positive clinical effect of parenteral infusions of amino acids is due, in addition to normalizing the ratio of amino acids, to a decrease in protein catabolism in the liver and muscles, as well as an improvement in metabolic processes in the brain. It should also be taken into account that branched chain amino acids are an important source of protein for patients with hepatic encephalopathy who require dietary protein restriction.
In severe forms of alcoholic hepatitis, in order to reduce endotoxemia and prevent bacterial infection, it is advisable to prescribe short courses of antibacterial drugs (preferably fluoroquinolones).
The range of drugs used in the complex treatment of diseases of the hepatobiliary system includes more than a thousand items. Among such a variety of drugs, there is a relatively small group of drugs that have a selective effect on the liver. These are hepatoprotectors. Their action is aimed at restoring homeostasis in the liver, increasing the organ’s resistance to the action of pathogenic factors, normalizing functional activity and stimulating reparative and regenerative processes in the liver.
Polyunsaturated (“essential”) phospholipids have the ability to reduce fatty liver changes, eliminate free radicals and suppress the activation of hepatic stellate cells. These properties have been demonstrated both in animal models and in patients with ALD.
Phospholipids (or phosphoglycerides) belong to the class of highly specialized lipids and are esters of glycerophosphoric acid. Phospholipids are also called essential, which shows their importance for the body as irreplaceable growth and development factors necessary for the functioning of all cells without exception. Their main purpose is that, along with cholesterol, they are the structural basis of cell membranes and organelle membranes. Phospholipids are important components of surfactant in the alveoli of the lungs, lipoproteins in blood plasma and bile. They take part in the functioning of the nervous system - without them the function of excitability and transmission of nerve impulses is impossible. Phospholipids in platelet membranes are essential in the blood clotting process to stop bleeding.
Phospholipids are the basis of biological membranes. Thus, phospholipids perform many functions in the body, but the main one is the formation of a double lipid layer in cell membranes. Biological membranes are the basis on which the most important life processes occur. Impaired functioning of biomembranes can be not only a cause, but also a consequence of the development of pathological processes. According to the currently generally accepted liquid mosaic model, the structure of biomembranes is a liquid crystalline bimolecular layer of lipids with hydrophobic groups on the outside and hydrophilic groups on the inside, in which peripheral and integral proteins move freely. The most common membrane lipids belong to the class of phospholipids; their double layer is stabilized by cholesterol molecules, proteins and glycolipids.
It is known that the role of the lipid component in the system is to create a certain hydrophobic matrix for enzymes, and the liquid state of the membrane itself makes it dynamic. If the enzyme is deprived of the lipid phase, it becomes unstable, aggregates and quickly loses activity, which depends largely on the physicochemical state of the lipid phase of the membrane. Consequently, the viscosity of the lipid bimolecular layer and the composition of lipids are the most important factors on which the activity of enzymes built into membranes depends. Cell membranes are associated with various enzyme systems - adenylate cyclase (cell membrane), cytochrome oxidase (mitochondrial membrane), as well as triglyceride lipase, lipoprotein lipase, cholesterol acyltransferase.
The hepatoprotective effect of essential phospholipids is also based on the inhibition of lipid peroxidation (LPO), which is considered one of the leading pathogenetic mechanisms for the development of liver damage. By restoring the “packaging” of polyunsaturated fatty acids in the hepatocyte membrane, essential phospholipids reduce the access of oxygen to them, thereby reducing the rate of formation of free radicals.
Several drugs of this group are registered on the Russian market, one of the most frequently prescribed is Essliver® Forte. A special feature of the drug is its combined composition: a combination of essential phospholipids and a complex of vitamins, which is especially important in conditions of vitamin deficiency in patients with alcoholic liver disease. In addition, the drug contains not only phospho-ti-dylcholine but also other types of phospholipids that play a great role in the formation of the cell cytoskeleton. Essliver® Forte contains vitamins B1, B2, B6, B12, tocopherol and nicotinamide. Vitamin B1 protects cell membranes from the toxic effects of peroxidation products, i.e. acts as an antioxidant and immunomodulator. Vitamin B2 is involved in the regulation of higher nervous activity. Vitamin B6 is a coenzyme for amino acid decarboxylases and transaminases that regulate protein metabolism. Vitamin B12 ensures the formation of the enzyme necessary for the production of lipoprotein in myelin tissue. Tocopherol is a natural antioxidant that protects polyunsaturated fatty acids and cell membrane lipids from peroxidation and free radical damage. It can perform a structural function by interacting with phospholipids of biological membranes. This composition provides Essliver® Forte with a wide range of therapeutic properties.
The literature describes a comparative multicenter study of the effectiveness of Essli-vera® Forte in patients with alcoholic liver disease in the stage of fatty degeneration and hepatitis. A statistically and clinically significant decrease in the severity of astheno-vegetative syndrome, normalization of the levels of ALT, AST, albumin, GGTP, globulins, total protein, prothrombin and alkaline phosphatase and an improvement in the ultrasound picture (decreased liver size, decreased its echogenicity and the height of the “sound attenuation column” in the liver). Statistically significant positive dynamics were also observed for glucose, total bilirubin and indirect bilirubin fraction, amylase; restoration of the protein-synthetic function of the liver and the synthesis of blood coagulation factors was noted. There was a significant improvement in quality of life assessments. Thus, the fairly high clinical effectiveness of Essliver® Forte is undeniable [Salikhov I.G., 2002].
It has been established that drugs of this group significantly accelerate liver recovery under toxic influences, slow down fibrosis and fatty infiltration of liver tissue, increase the synthesis of RNA and protein by cells, and accelerate regeneration. Phospholipids provide hepatoprotective and epidermis-targeted effects.
Essential phospholipid preparations are compatible with other pharmaceuticals and nutrients. The bioavailability of phospholipids is approximately 90% of the administered amount. In addition, phosphatidylcholine increases the bioavailability of nutrients with which it is coadministered.
Ademetionine - has a detoxifying, regenerating, antioxidant, antifibrinizing, neuroprotective effect, acts as a metabolic substrate for the most important biochemical reactions in the body. The therapeutic effect of ademetionine lies in the intracellular reaction of glutathione synthesis. Glutathione is known to prevent liver damage. With a sufficient amount of glutathione, the hepatocyte is least susceptible to the toxic effects of ethanol metabolites, and under certain conditions even their detoxification can occur. Synthesis of glutathione with the introduction of ademetionine in a daily dose of 800 mg intravenously for 7-14 days, with a transition to administration in tablet form of 400-800 mg (1-2 tablets) for 14 days leads to the restoration of liver function and normalization of clinical symptoms. laboratory signs. Ademetionine, which restores the structure and properties of cell membranes, as well as restoring intracellular glutathione reserves, according to some data, increases survival and delays the timing of liver transplantation in severe forms of acute alcoholic hepatitis.
Plant-based preparations (active principle - silymarin) stabilize the cell membrane, restoring damaged liver cells.
The use of ursodeoxycholic acid is pathogenetically justified, especially in the cholestatic variant of acute alcoholic hepatitis, but there is currently insufficient data on its clinical effectiveness.
The attitude towards glucocorticoids in alcoholic hepatitis remains ambiguous. Data from a meta-analysis of 13 randomized controlled trials indicate a significant increase in immediate survival of patients with severe OAS (with a Maddrey index >32 and/or hepatic encephalopathy). The standard course is 40 mg of prednisolone or 32 mg of methylprednisolone per os per day for 4 weeks. It is important to note that these data relate to survival during the current hospitalization, since the differences between the main and control groups level out after 1-2 years, which is due to decompensation of background cirrhosis and/or repeated episodes of acute alcoholic hepatitis. When prescribing prednisolone, careful monitoring of the patient is necessary due to the increased risk of infectious complications, gastrointestinal bleeding, hyperglycemia and renal failure.
In recent years, accumulated data on the role of pro-inflammatory cytokines in the pathogenesis of alcoholic hepatitis have served as the basis for the introduction of drugs with anti-cytokine properties into clinical practice.
Thus, at present, for the treatment of alcoholic hepatitis, there are modern, highly effective means that can cure the disease or stabilize the condition of the diseased organ and the body as a whole for a long time, preventing the development of cirrhosis of the liver or a tumor process.

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