Acute alcoholic hepatitis: causes, symptoms, diagnosis, treatment

Alcoholic hepatitis is detected in approximately 35% of patients with chronic alcoholism. In clinical terms, it is proposed to distinguish acute and chronic alcoholic hepatitis.

Acute alcoholic hepatitis (AAH) is an acute degenerative and inflammatory liver disease caused by alcohol intoxication, morphologically characterized mainly by centripetal necrosis, an inflammatory reaction with infiltration of the portal fields mainly by polynuclear leukocytes and the detection of alcoholic hyaline (Mallory bodies) in hepatocytes.

The disease develops mainly in men who abuse alcohol for at least 5 years. However, when consuming large amounts of alcohol, acute alcoholic hepatitis can develop very quickly (within a few days of binge drinking, especially if it is repeated several times). Acute alcoholic hepatitis is predisposed by insufficient, unhealthy nutrition, as well as a genetic predisposition to alcoholism and alcoholic liver disease.

As a rule, alcoholic hepatitis begins acutely after a previous binge, pain in the liver area, jaundice, nausea, and vomiting quickly appear.

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Histological manifestations

Acute alcoholic hepatitis is characterized by the following histological manifestations:

• perivenular centrilobular hepatocyte damage (balloon dystrophy of hepatocytes in the form of their swelling with an increase in size, clearing of the cytoplasm and karyopyknosis; necrosis of hepatocytes mainly in the center of the liver lobules);
• the presence of alcoholic hyaline (Mallory bodies) in hepatocytes. It is assumed that it is synthesized by the granular endoplasmic reticulum and is detected centrilobularly using a special three-color stain according to Mallory. Alcoholic hyaline reflects the severity of liver damage and has antigenic properties, includes immune mechanisms for further progression of alcoholic liver disease;
• as alcoholic hepatitis subsides, alcoholic hyaline is detected less frequently;
• inflammatory infiltration by segmented leukocytes and, to a lesser extent, lymphocytes of the liver 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 hepatocytes.

Symptoms of acute alcoholic hepatitis

The following clinical variants of acute alcoholic hepatitis are distinguished: latent, icteric, cholestatic, fulminant and a variant with severe portal hypertension.

Latent variant

The latent variant of acute alcoholic hepatitis is asymptomatic. However, many patients complain of poor appetite, mild pain in the liver, an enlarged liver, moderate increase in aminotransferase activity in the blood serum, and possible development of anemia and leukocytosis. For accurate diagnosis of the latent variant of acute alcoholic hepatitis, a puncture liver biopsy and histological analysis of the biopsy are necessary.

Jaundice variant

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

• patients complain of severe general weakness, complete loss of appetite, fairly intense pain in the right hypochondrium of a constant nature, nausea, vomiting, and significant weight loss;
• severe jaundice appears, not accompanied by itching of the skin;
• body temperature rises, the fever lasts for at least two weeks;
• In some patients, splenomegaly and palmar erythema are detected, and in some cases ascites develops;
• in severe cases of the disease, symptoms of hepatic encephalopathy may appear;
• laboratory data: leukocytosis with an increase in the number of neutrophilic leukocytes and a band shift, an increase in ESR; hyperbilirubinemia with a predominance of the escorted fraction, an increase in the activity of aminotransferases (mainly aspartic), alkaline phosphatase, y-glutamyl transpeptidase in the blood serum, a decrease in the content of albumins and an increase in y-globulins.

The icteric variant of acute alcoholic hepatitis must be differentiated from 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 of the skin;
• jaundice;
• dark urine;
• light-colored feces (acholia);
• The blood bilirubin content is significantly increased, mainly due to the conjugated fraction, cholesterol, triglycerides, alkaline phosphatase, and y-glutamyl transpeptidase; however, the increase in aminotransferase activity is small.

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Fulminant variant

The fulminant variant of acute alcoholic hepatitis is characterized by a severe, rapid, progressive course. Patients are concerned about pronounced general weakness, complete loss of appetite, intense pain in the liver and epigastrium, high body temperature, rapidly increasing jaundice, developing ascites, hepatic encephalopathy, renal failure, and possible hemorrhagic phenomena. Laboratory data reflect a pronounced syndrome of hepatocyte cytolysis (increased serum activity of aminotransferases, fructose-1-phosphate albdolase, ornithine carbamoyltransferase), hepatocellular insufficiency (decreased blood albumin levels, prolonged prothrombin time), inflammation (significant increase in ESR, leukocytosis with a left shift in the leukocyte formula).

The fulminant variant of acute alcoholic hepatitis can end in death within 2-3 weeks from the onset. Death occurs from liver or liver-renal failure.

Diagnosis of acute alcoholic hepatitis

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

Serum transaminase activity is elevated, but rarely exceeds 300 IU/L. Very high transaminase activity indicates hepatitis complicated by paracetamol intake. The AST/ALT ratio exceeds 2/1. Alkaline phosphatase activity is usually elevated.

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

The serum potassium level is low, largely due to inadequate dietary protein intake, diarrhea, and secondary hyperaldosteronism if fluid retention is present. The serum albumin-bound zinc level is reduced, which in turn is due to low liver zinc concentrations. This feature is not found in patients with nonalcoholic liver disease. Blood urea and creatinine levels are elevated, reflecting the severity of the condition. These indicators are predictors of the development of hepatorenal syndrome.

According to the severity of alcoholic hepatitis, an increase in the number of neutrophils is observed, usually reaching 15–20•10 ⁹ /l.

Platelet function is reduced even in the absence of thrombocytopenia or alcohol in the blood.

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Treatment of acute alcoholic hepatitis

• Stopping drinking alcohol
• Identification of aggravating factors (infections, bleeding, etc.)
• Prevention of the development of acute alcohol withdrawal syndrome
• Intramuscular administration of vitamins
• Treatment of ascites and encephalopathy
• Adding potassium and zinc
• Maintenance of nitrogen-containing substances intake orally or enterally
• Consideration of corticosteroids in severe disease with encephalopathy but without gastrointestinal bleeding

Caution should be exercised when treating ascites, as there is a risk of developing functional renal failure.

The results of corticosteroid use are extremely contradictory. In seven clinical studies involving patients with mild to moderate acute alcoholic hepatitis, corticosteroids did not affect clinical recovery, biochemical parameters, or progression of morphologic changes. However, more favorable results were obtained in a randomized multicenter study. The study included patients with both spontaneous hepatic encephalopathy and with a discriminant function greater than 32. Seven days after admission, patients were given methylprednisolone (30 mg/day) or placebo; these doses were used for 28 days, and then gradually tapered over 2 weeks, after which administration was stopped. Mortality among 31 patients receiving placebo was 35%, and among 35 patients taking prednisolone, it was 6% (P = 0.006). Thus, prednisolone reduced early mortality. This drug seems to be particularly effective in patients with hepatic encephalopathy. In the treated group, the reduction in serum bilirubin and the decrease in PT were greater. Randomized trials and a meta-analysis of all trials have confirmed the effectiveness of corticosteroids in terms of early survival. These results are difficult to reconcile with the negative results of the previous 12 trials, many of which, however, included only small numbers of patients. They may have been subject to type I (control and corticosteroid groups were not comparable) or type II (inclusion of too many patients who were not at risk of death) errors. It is possible that the patients in the latter trials were less severely ill than those in the earlier trials. Corticosteroids appear to be indicated in patients with hepatic encephalopathy but without bleeding, systemic infections, or renal failure. Only approximately 25% of hospitalized patients with alcoholic hepatitis meet all of the above criteria for corticosteroid use.

Minimum nutritional and energy value of the daily diet of patients with alcoholism

Chemical composition and energy value	Quantity	Notes
Squirrels	1 g per 1 kg of body weight	Eggs, lean meats, cheese, chicken, liver
Calories	2000 kcal	A variety of foods, fruits and vegetables
Vitamins
A	One tablet of multivitamin	Or one carrot
Group B		Or yeast
WITH		Or one orange
D		Sunlight
Folates		A complete and varied diet
K1		A complete and varied diet

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

Severe protein deficiency contributes to decreased immunity and the development of infectious diseases, aggravates hypoalbuminemia and ascites. In this regard, the importance of adequate nutrition is obvious, especially in the first few days of hospital stay. Most patients can receive an adequate amount of natural proteins with food. The improvement of the patient's condition can be accelerated by the use of additional nutrition in the form of casein, which is administered using a nasoduodenal tube (1.5 g of protein per 1 kg of body weight). However, the increase in the survival rate of such patients is only a tendency.

Controlled studies with intravenous amino acid supplementation have yielded conflicting results. In one study, daily administration of 70–85 g amino acids reduced mortality and improved serum bilirubin and albumin levels; in another, the effect was short-lived and modest. In a subsequent study, patients receiving this treatment had an increased incidence of sepsis and fluid retention, although serum bilirubin levels were reduced. Supplementation with branched-chain amino acids has not been shown to affect mortality. Oral or intravenous amino acid supplementation should be reserved for a very small number of patients with jaundice and severe malnutrition.

Colchicine did not improve early survival in patients with alcoholic hepatitis.

Propylthiouracil. Alcohol-induced metabolic enhancement potentiates hypoxic liver injury in zone 3. Propylthiouracil attenuates hypoxic liver injury in animals with a hypermetabolic state; the drug has been used to treat patients with alcoholic liver disease, primarily at the cirrhotic stage. A controlled study confirmed the efficacy of the drug, especially at a late stage, in patients who continued to drink alcohol in smaller quantities. However, propylthiouracil has never been approved for the treatment of alcoholic liver disease.

Prognosis for acute alcoholic hepatitis

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

Acute alcoholic hepatitis is characterized by a high frequency of its transition to liver cirrhosis (in 38% of patients over 5 years), complete recovery from acute alcoholic hepatitis is observed only in 10% of patients, provided that alcohol intake is completely stopped, but, unfortunately, in some patients, abstinence does not prevent the development of liver cirrhosis. Probably, in this situation, the mechanisms of self-progression of liver cirrhosis are activated.

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