Acute alcoholic hepatitis: causes, symptoms, diagnosis, treatment

Alcoholic hepatitis is detected in approximately 35% of patients with chronic alcoholism. Clinically, it is proposed to isolate acute and chronic alcoholic hepatitis.

Acute alcoholic hepatitis (OAH) - acute degenerative and inflammatory liver damage caused by alcohol intoxication, morphologically characterized mainly by centrally glossy necrosis, inflammatory reaction with portal field infiltration mainly by polynucleated leukocytes and detection of alcoholic hyaline (Mallory corpuscles) in hepatocytes.

The disease develops mainly in men who abuse alcohol for at least 5 years. However, if you consume large amounts of alcohol, acute alcoholic hepatitis can develop very quickly (within a few days of drinking alcohol, especially if it repeatedly repeats). To acute alcoholic hepatitis predisposes insufficient, irrational nutrition, as well as genetic burden in terms of alcoholism and alcoholic liver damage.

As a rule, alcoholic hepatitis begins acutely after the previous binge, quickly there are pains in the liver, jaundice, nausea, vomiting.

[1], [2], [3], [4]

Histological manifestations

For acute alcoholic hepatitis, the following histological manifestations are characteristic:

• periveneular centrolobular lesion of hepatocytes (balloon dystrophy of hepatocytes in the form of their swelling with increase in size, clarification of the cytoplasm and karyopicnosis, hepatocyte necrosis mainly in the center of the hepatic lobules);
• presence in hepatocytes of alcoholic hyaline (Mallory corpuscles). It is supposed that it is synthesized by a granular endoplasmic reticulum, it is detected centrally by means of a special three-color color according to Mallory. Alcoholic hyaline reflects the severity of liver damage and has antigenic properties, includes immune mechanisms for the further progression of alcoholic liver disease;
• As alcohol alcoholic hepatitis decreases, alcoholic hyaline is less likely to be detected;
• inflammatory infiltration of segmented leukocytes and, to a lesser extent, lymphocytes of hepatic lobules (in foci of necrosis and around hepatocytes containing inclusions of alcoholic hyaline) and portal tracts;
• pericellular fibrosis - the development of fibrous tissue along the sinusoids and around the hepatocytes.

Symptoms of acute alcoholic hepatitis

Distinguish the following clinical variants of acute alcoholic hepatitis: latent, icteric, cholestatic, fulminant and variant with severe portal hypertension.

Latent variant

The latent variant of acute alcoholic hepatitis proceeds asymptomatically. However, many patients have complaints of poor appetite, low-intensity pain in the liver, a liver enlargement, a moderate increase in serum aminotransferase activity, possibly anemia, leukocytosis. To accurately diagnose a latent variant of acute alcoholic hepatitis, puncture liver biopsy and a histological analysis of the biopsy are needed.

Jaundice variant

The icteric variant is the most frequent variant of acute alcoholic hepatitis. It is characterized by the following clinical and laboratory symptoms:

• patients complain of a pronounced general weakness, a complete lack of appetite, a fairly intense pain in the right hypochondrium of a permanent nature, nausea, vomiting, a significant decrease in body weight;
• there is severe jaundice, not accompanied by pruritus;
• body temperature rises, fever lasts at least two weeks;
• in some patients, splenomegaly, palmar erythema are defined, in some cases ascites develops;
• in severe cases, the appearance of symptoms of hepatic encephalopathy;
• laboratory data: leukocytosis with an increase in the number of neutrophilic leukocytes and a stab-shift, an increase in ESR; hyperbilirubinemia with a predominance of the convoy fraction, an increase in serum aminotransferase activity (predominantly aspartic), alkaline phosphatase, y-glutamyltranspeptidase, a decrease in albumin content, and an increase in y-globulin.

The icteric variant of acute alcoholic hepatitis must be differentiated with acute viral hepatitis.

Cholestatic variant

This variant of acute alcoholic hepatitis is characterized by the appearance of clinical and laboratory signs of intrahepatic cholestasis:

• intense itching;
• jaundice;
• dark urine;
• light feces (acholia);
• in the blood, the bilirubin content is significantly increased mainly due to the conjugated fraction, cholesterol, triglycerides, alkaline phosphatase, y-glutamyltranspeptidase; In addition, the increase in aminotransferase activity is small.

[5], [6], [7], [8], [9], [10], [11]

Fulminant variant

The fulminant variant of acute alcoholic hepatitis is characterized by a severe, rapid, progressive course. Patients are worried about a pronounced general weakness, complete lack of appetite, intense pain in the liver and epigastrium, high body temperature, jaundice is rapidly increasing, ascites, hepatic encephalopathy, renal failure, hemorrhagic phenomena are possible. The laboratory data reflect the pronounced cytolysis syndrome of hepatocytes (an increase in the activity of aminotransferases, fructose-1-phosphatalvdolase, ornithine carbamoyltransferase in the serum of blood), hepatocellular insufficiency (decrease in albumin blood, prolongation of prothrombin time), inflammation (significant increase in ESR, leukocytosis with shift of leukocyte formula to the left ).

The fulminant variant of acute alcoholic hepatitis can result in a fatal outcome within 2-3 weeks from the beginning. Death comes from hepatic or hepatic renal failure.

Diagnosis of acute alcoholic hepatitis

• General blood test: leukocytosis (10-30x109 / l) with an increase in the number of neutrophils, with a stab shift, an increase in ESR; some patients develop anemia;
• Biochemical blood test: increase of bilirubin in the blood to 150-300 μmol / l with a predominance of conjugated fraction; an increase in the activity of aminotransferases with a predominance of aspartic, y-glutamyltanespeptidase; hypoalbuminemia; hypoprothrombinemia.

The activity of serum transaminases is increased, but rarely exceeds 300 IU / L. The very high activity of transaminases indicates hepatitis, complicated by the use of paracetamol. The ASAT / ALAT ratio is greater than 2/1. As a rule, the activity of alkaline phosphatase is increased.

The severity of the disease is best indicated by the serum bilirubin level and prothrombin time (PT), determined after the appointment of vitamin K. The serum IgA level is markedly increased; concentrations of IgG and IgM increase much less; IgG level decreases as the condition improves. In the serum, the albumin content is reduced, which rises as the patient's condition improves, and the cholesterol level is usually elevated.

The level of potassium in the serum is low, which is largely due to insufficient intake of food proteins, diarrhea and secondary hyperaldosteronism, if there is fluid retention. The serum content of albumin-bound zinc is reduced, which in turn is due to low zinc concentration in the liver. This symptom is not found in patients with non-alcoholic liver damage. The blood level of urea and creatinine, which reflects the severity of the condition. These indicators are predictors of the development of hepatorenal syndrome.

Accordingly, the severity of alcoholic hepatitis shows an increase in the number of neutrophils, usually reaching 15-20 × 10 ⁹ / L.

The function of platelets is lowered when there is no thrombocytopenia or alcohol in the blood.

[12], [13], [14], [15],

Treatment of acute alcoholic hepatitis

• Cessation of alcohol use
• Identification of aggravating factors (infection, bleeding, etc.)
• Prevention of the development of alcohol withdrawal syndrome
• Intramuscular administration of vitamins
• Treatment of ascites and encephalopathy
• Addition of potassium and zinc
• Maintaining the intake of nitrogen-containing substances orally or enterally
• Consideration of the possibility of the appointment of corticosteroids in severe disease with encephalopathy, but without gastrointestinal bleeding

Care should be taken in the treatment of ascites, as there is a possibility of developing functional renal failure.

The results of the use of corticosteroids are extremely controversial. In 7 clinical trials involving patients with acute alcoholic hepatitis of mild or moderate severity, corticosteroids did not affect clinical recovery, biochemical indices or progression of morphological changes. However, in a randomized, multicenter study, more favorable results were obtained. The study involved patients with both spontaneous hepatic encephalopathy and with a discriminant function above 32. Seven days after admission, patients were prescribed methylprednisolone (30 mg / day) or placebo; such doses were applied for 28 days, and then for 2 weeks they gradually decreased, after which the reception ceased. Mortality among the 31 patients receiving placebo was 35%, and among the 35 patients taking prednisolone, -6% (P = 0.006). Thus, prednisolone reduced early mortality. This drug seems particularly effective in patients with hepatic encephalopathy. In the group of patients treated, the reduction in serum bilirubin and the decrease in PV were more significant. Randomized studies and a meta-analysis of all studies have confirmed the efficacy of corticosteroids for early survival. These results are difficult to reconcile with the negative results of the previous 12 studies, many of which, however, involved only a small number of patients. Perhaps, mistakes of type I were made (the control group and the group of patients receiving corticosteroids were not comparable) or type II (inclusion of too many patients who did not face death). Perhaps the patients who participated in the latest studies were less severe than the patients in previous studies. Apparently, corticosteroids are indicated to patients with hepatic encephalopathy, but without bleeding, systemic infections or renal insufficiency. Only about 25% of hospitalized patients with alcoholic hepatitis meet all of the above criteria for the use of corticosteroids.

The minimum nutritional and energy value of the daily diet of alcoholics

Chemical composition and energy value	Amount	Notes
Proteins	1 g per 1 kg of body weight	Eggs, lean meat, cheese, chicken, liver
Calories	2000 kcal	Varied food, fruits and vegetables
Vitamins
A	One tablet of multivitamins	Or one carrot
Group B		Or yeast
FROM		Or one orange
D		Sunlight
Folates		A full varied diet
K1		A full varied diet

Testosterone is ineffective. Oxandrolone (anabolic steroid) is useful for patients with moderate severity of the disease, but is ineffective in patients with malnutrition and low caloric intake.

Heavy protein deficiency contributes to a decrease in immunity and the occurrence of infectious diseases, exacerbates hypoalbuminemia and ascites. In this regard, the importance of adequate nutrition is evident, especially in the first few days of hospital stay. Most patients can receive an adequate amount of natural proteins with food. Improvement of the patient's condition can be accelerated after using supplementary nutrition in the form of casein, which is injected with a nasode-duodenal probe (1.5 g protein per 1 kg body weight). However, the increase in the survival rate of such patients is only a trend in nature.

Controlled studies with intravenous administration of amino acid supplements produced conflicting results. In one study, daily administration of 70-85 g of amino acids reduced mortality and improved bilirubin and albumin levels in serum, while in another, the effect of such treatment was short-term and insignificant. In the next study, the incidence of sepsis and fluid retention increased in patients receiving this treatment, although the serum bilirubin level decreased. It is shown that the enrichment of food with branched-chain amino acids does not affect the mortality rate. Oral or intravenous administration of amino acid supplements should be reserved for a very small number of patients with jaundice and severe malnutrition.

Colchicine did not improve the early survival of patients with alcoholic hepatitis.

Propylthiouracil. Increased metabolism caused by alcohol potentiates hypoxic liver damage in zone 3. Propylthiouracil weakens hypoxic liver damage in animals with hypermetabolic condition; This drug was used to treat patients with alcoholic liver disease, mainly at the stage of cirrhosis. A controlled study confirmed the efficacy of this drug, especially at a later date, in those patients who continued to consume less alcohol. Nevertheless, Propylthiouracil has never been approved for the treatment of alcoholic liver disease.

Forecast for acute alcoholic hepatitis

The prognosis for acute alcoholic hepatitis depends on the severity of its course, as well as on the severity of abstinence from alcohol. Severe forms of acute alcoholic hepatitis can lead to death (lethal outcome is observed in 10-30% of cases). Relapses of acute alcoholic hepatitis against the background of previously formed cirrhosis lead to its steady progression, decompensation and development of severe complications (severe portal hypertension, gastrointestinal bleeding, hepatic renal failure).

Acute alcoholic hepatitis is characterized by a high incidence of its transition to cirrhosis of the liver (in 38% of patients for 5 years), complete recovery in acute alcoholic hepatitis is observed only in 10% of patients with complete cessation of alcohol intake, but, unfortunately, in some patients Abstinence does not prevent the development of cirrhosis. Probably, in this situation, the mechanisms of self-progressive cirrhosis of the liver are included.

[16], [17],