Mario Tanno and Hugo Tanno
Liver damage from alcohol encompasses a broad spectrum of clinicopathological entities, ranging from simple steatosis to decompensated cirrhosis. A subset of patients, mainly those who ingest large amounts of alcohol, develop an acute form, with severe liver damage. This clinical syndrome is called alcoholic hepatitis and is characterized by the presence of fever, hepatomegaly, and leukocytosis that are associated with clinical and laboratory findings typical of liver failure.
Ethanol is rapidly absorbed from the gastrointestinal tract and most of it is metabolized in the liver.
Classically, three metabolic pathways are described: 1) alcohol dehydrogenase, 2) cytochrome P-450 and 3) catalases.
In the first pathway, ethanol is oxidized to acetaldehyde in the cytosol of the hepatocyte by the enzyme alcohol dehydrogenase (ADH). Acetaldehyde is a highly toxic molecule for the body, being rapidly oxidized in the mitochondria, producing acetate. This process is mediated by the enzyme aldehyde dehydrogenase (ALDH)
The second pathway involves an enzyme complex located in the smooth endoplasmic reticulum membrane, known as cytochrome P-450 reductase (Fig 1). This microsomal complex has a portion with alcohol-inducible activity and as consumption increases, the ability to metabolize it also increases. This enzyme complex is called the microsomal oxidative system of ethanol (SOME).
The third pathway, that of catalases, has an irrelevant role in human pathophysiology.
Mechanisms of cellular injury.
When the microsomal activity increases, the leakage of reactive oxygen species occurs, which are free radicals capable of damaging proteins, nucleic acids and organelles of the liver cell. The increase in free radicals leads to the activation of the Kupffer cell which begins to produce different cytokines. These produce inflammation and apoptosis in the liver parenchyma with an increase in polymorphonuclear cells, whose infiltrate is characteristic of alcoholic hepatitis.
Lipopolysaccharides are products that constitute the capsule of the Gram negative bacilli of the intestinal flora, they are increased in the portal circulation of alcoholic patients, due to an increase in intestinal permeability. These polysaccharides have the ability to activate the Kupffer cell producing effects similar to free radicals.
The stellate cell is activated by mechanisms very similar to that of the Kuppfer cell, with the consequent production of fibrosis. This explains the evolution to cirrhosis in those patients who continue with alcohol intake.
Signs and symptoms
Patients with alcoholic hepatitis may present with fever, jaundice, hepatomegaly, and occasionally signs of decompensated chronic liver disease such as ascites, gastrointestinal bleeding, and hepatic encephalopathy. Asthenia, anorexia, nausea, and vomiting are common. However, there are completely asymptomatic patients with alcoholic hepatitis.
The presence of fever makes it necessary to rule out other origins, such as the existence of an infection or the development of delirium tremens after the abrupt suspension of alcohol intake. The cutaneous stigmata of advanced chronic disease suggest the presence of cirrhosis. 70% of patients with laboratory moderate or severe hepatitis are already cirrhotic at the time of diagnosis.
One of the most common alterations in the laboratory is the presence of leukocytosis with significant neutrophilia. Alanine aminotransferase (ALT) and aspartate aminotransaferase (AST) are moderately increased, with a predominance of the latter. An AST / ALT ratio greater than 2 helps differentiate liver damage caused by alcohol from that caused by viral hepatitis in which ALT predominates. Gamma-glutamyltranspeptidase (GGT) is very high, due in part to cell damage and its induction by the action of alcohol. Cholestasis with conjugated hyperbilirubinemia and elevated alkaline phosphatase are common. Macrocytic anemia is secondary to alcoholism and nutritional deficiencies, with thrombocytopenia being frequently observed. Laboratory parameters are useful to establish prognosis, The so-called Madrey discriminant function can calculate short-term mortality. Its formula is simple and easy to apply in clinical practice:
Discriminant function = 4.6 x (Patient prothrombin time - Control prothrombin time) + serum bilirubin in mg / dL
If the value obtained is greater than 32, the short-term mortality is 50%
Ultrasound, Tomography and Magnetic Resonance are useful to evaluate the presence of cirrhosis and rule out venous obstructions, or the presence of hepatocarcinoma.
Liver biopsy is limited by the coagulatory abnormalities that these patients often present. The characteristic findings are infiltration with a predominance of neutrophils, perivenular fibrosis, hepatocellular necroapoptosis, and the presence of Mallory's hyaline bodies.