| disease | Alcoholic Hepatitis |
| alias | Alcoholic Hepatitis |
Alcoholic Hepatitis refers to a liver disease caused by long-term excessive alcohol consumption. Its main clinical features include nausea, vomiting, jaundice, liver enlargement, and tenderness. It may be complicated by liver failure and upper gastrointestinal bleeding.
bubble_chart Etiology
The incidence of alcoholic hepatitis and the severity of liver damage are linearly and positively correlated with both the duration of heavy drinking and the dose. In developed countries in Europe and America, the incidence is significantly higher than in China, and there is an increasing trend of severe alcoholic liver damage among women. Approximately 10–20% of heavy drinkers have varying degrees of alcoholic liver disease. Over 90% of ethanol is oxidized and metabolized in the liver to produce acetaldehyde and acetic acid. During the oxidation of ethanol by alcohol dehydrogenase and microsomal enzymes, as well as the oxidation of acetaldehyde to acetate or acetyl-CoA, NAD+ is reduced to NADH, causing the intracellular environment to become reduced. This interferes with the metabolism of carbohydrates, lipids, and some intermediate metabolic pathways. Reduced gluconeogenesis, increased synthesis of fatty acids and triglycerides, and the reduction of oxaloacetate to malate, which weakens the activity of the citric acid cycle, can lead to hypoglycemia, hypertriglyceridemia, fat accumulation in the liver, and disruption of energy metabolism. The reduction of pyruvate to lactate can promote the occurrence of hyperuricemia and acidosis. Ethanol and acetaldehyde have direct toxic effects on the liver. Long-term heavy drinking can enhance the hepatotoxicity of commonly used drugs, certain vitamins, environmental hepatotoxic substances, and carcinogens.
bubble_chart Pathological ChangesAlcoholic liver disease pathologically manifests as a trilogy: fatty liver → alcoholic hepatitis → cirrhosis, with frequent overlap among the three. The histological features of alcoholic hepatitis include acute or chronic liver inflammation, characterized by hepatocyte vacuolar degeneration, necrosis, alcoholic hyaline bodies (Mallory bodies), intralobular infiltration of neutrophils and lymphocytes, fibrous tissue proliferation, and bile stasis. Perivenular fibrosis or sclerosing hyaline necrosis in terminal hepatic venules can occur before cirrhosis, leading to portal hypertension. Mallory bodies are specific pathological changes in alcoholic hepatitis but are also observed in certain cases of primary biliary cirrhosis, Wilson's disease, Indian childhood cirrhosis, post-small intestinal bypass cirrhosis, and hepatocellular carcinoma. These bodies result from cytoplasmic fibrin deposition, appearing as irregularly shaped, variably sized, high-density eosinophilic substances near hepatocytes, which may contain small amounts of fat. Mallory bodies measure 2–3 μm in diameter, presenting as filamentous, irregularly arranged, or horseshoe-shaped structures surrounding hepatocyte nuclei. Under electron microscopy, these bodies consist of numerous irregular intermediate filaments.
bubble_chart Clinical Manifestations
Since alcoholic hepatitis is a histopathological diagnosis, its clinical manifestations vary widely in severity, ranging from asymptomatic to jaundice, and can even lead to death from complications. It often develops from fatty liver and may overlap with cirrhosis.
1. Symptoms
Patients often have a recent history of heavy alcohol consumption and may experience loss of appetite, nausea, vomiting, abdominal pain, and weight loss, along with fever. The severity of symptoms usually correlates with the degree of histological changes in the liver, but some patients may have no symptoms at all. A literature review reported that among 89 patients with liver biopsy-confirmed alcoholic hepatitis, 51% of those with serum total bilirubin ≤85.5 μmol/L had no liver-related symptoms.
The disease is characterized by jaundice, hepatomegaly, and tenderness. Hepatomegaly is present in 80–100% of patients. Ascites, fever, splenomegaly, spider angiomas, and neuropsychiatric symptoms occur in 10–70% of cases. Some patients may exhibit moderate bilateral parotid gland enlargement.
bubble_chart Auxiliary Examination
1. Hematological examination
may reveal anemia, leukocytosis, and the presence of abnormal red blood cells such as target cells, acanthocytes, stomatocytes, and macrocytes, with an increased mean corpuscular volume (MCV).
2. Generation and transformation examination
shows elevated serum bilirubin, a significant increase in aspartate aminotransferase (AST) activity, while alanine aminotransferase (ALT) activity only rises to grade I or remains normal. Consequently, the AST:ALT ratio increases. When the ratio exceeds 2, the sensitivity for diagnosing alcoholic liver disease is 68%, specificity reaches 91%, and the positive predictive value is 82%. Alkaline phosphatase and gamma-glutamyl transpeptidase (γ-GT) activities are also elevated. γ-GT is a sensitive but non-specific indicator. The combined detection of MCV, γ-GT, and alkaline phosphatase is an ideal laboratory indicator for diagnosing alcoholic liver disease.
3. Liver B-ultrasound and CT examination
can help detect fatty liver. Definitive diagnosis relies on liver biopsy. Since liver damage is diffuse, non-targeted percutaneous biopsy can be performed.
Based on the patient's history of long-term heavy alcohol abuse; clinical symptoms such as fever, jaundice, hepatomegaly with tenderness, and elevated white blood cell count; increased MCV, r-GT, alkaline phosphatase, and AST/ALT ratio >2 all support the diagnosis of alcoholic hepatitis. However, a definitive diagnosis requires a liver biopsy for pathological examination. Misdiagnosis often occurs due to inferring liver histological changes based on conventional laboratory results, as the correlation between enzyme changes and histopathology in alcoholic liver disease is extremely poor. A study reported that among 89 patients with liver biopsy-confirmed alcoholic hepatitis, 49% had normal serum bilirubin, 19% had normal AST levels, 37% showed no increase in alkaline phosphatase, and 59% had normal serum albumin levels. However, within 30 months, 38% developed cirrhosis, with a mortality rate of 22%.
Patients with alcoholic hepatitis should quit drinking as early as possible. Those with obvious symptoms and signs should be hospitalized for bed rest and receive comprehensive treatment measures.
1. Nutritional Therapy
Patients with this disease should consume a nutritious diet high in vitamins, protein, calories, magnesium, and zinc. Due to reduced glycogen reserves in the liver of alcoholic liver disease patients, decreased food intake can enhance protein catabolism. However, in severe cases, loss of appetite, and even nausea and vomiting limit caloric intake. Therefore, parenteral administration of a solution containing branched-chain amino acids, compound formula amino acids, glucose, and small amounts of lipids can improve nutritional status and alleviate negative nitrogen balance. Some reports suggest it can increase plasma albumin, reduce serum bilirubin, and lower mortality rates.
2. Corticosteroids
Recent studies on immune mechanisms suggest that corticosteroids can modulate cytokine production and release, particularly interleukin II and tumor necrosis factor, thereby improving the inflammatory response in alcoholic hepatitis. They have a definite therapeutic effect on severe cases and can significantly reduce mortality in patients complicated with hepatic encephalopathy, but their efficacy in mild cases is unclear. Female patients with alcoholic hepatitis primarily characterized by cholestasis may benefit from a one-month course of 40 mg prednisone daily. However, since corticosteroids can induce upper gastrointestinal bleeding and infections, they should be used cautiously in patients with sepsis, diabetes, or active upper gastrointestinal bleeding.
3. Propylthiouracil (PTU)
Some studies report that hepatic oxygen consumption increases during ethanol metabolism. Thyroidectomy and propylthiouracil can alleviate hypoxia-induced injury around central veins. PTU may improve short-term and long-term survival rates in alcoholic hepatitis, but other studies indicate it does not reduce mortality and may cause hypothyroidism. Therefore, further research is needed to confirm this therapy before widespread application.
The prognosis of alcoholic hepatitis is related to the extent of acute liver injury and whether it is complicated by cirrhosis. The presence of hepatic encephalopathy, ascites, spider angiomas, renal failure, or a prothrombin time prolonged by more than 50% compared to the control can all increase mortality. If alcohol cessation and hospitalization are timely, most patients can recover, with mortality dropping below 10%. The main causes of death are liver failure and acute pancreatitis. Continued alcohol consumption can lead to cirrhosis, with a 5-year survival rate of only 34.1% to 68.2%.
1. Liver failure The condition deteriorates rapidly after onset, with clinical manifestations similar to severe liver disease. Hepatic encephalopathy often occurs.
2. Upper gastrointestinal bleeding Due to increased portal pressure and/or coagulation disorders, esophageal or gastric varices or acute gastric mucosal lesions lead to upper gastrointestinal bleeding.
3. Intrahepatic cholestasis Manifested by significant hepatomegaly, deepening jaundice, fever, markedly elevated direct bilirubin and alkaline phosphatase, but only grade I elevation of transaminases.
4. Alcoholic hyperlipidemia-hemolysis (Zieve) syndrome This syndrome presents as a triad of jaundice, hyperlipidemia, and hemolytic anemia. Recovery occurs after alcohol cessation, with a good prognosis.
5. Nutritional disorders Manifestations include anemia, folic acid deficiency, peripheral neuritis, Wernicke's disease, etc. Prone to concurrent infections, including pulmonary and subcutaneous nodules. {|104|}
The differential diagnosis should clarify whether it is chronic alcoholism or alcoholic liver disease; if it is alcoholic liver disease, determine which stage it belongs to; and differentiate it from other liver diseases. Among these, blood alcohol concentration measurement and liver biopsy are the most important diagnostic tools. This condition should be differentiated from liver abscess, biliary diseases, metastatic liver cancer, and sepsis.
