Alcoholic hepatitis
Encyclopedia
Alcoholic hepatitis is hepatitis
(inflammation of the liver) due to excessive intake of alcohol
. While distinct from cirrhosis
, it is regarded as the earliest stage of alcoholic liver disease
. Symptoms are jaundice
, ascites
(fluid accumulation in the abdominal cavity
), fatigue and hepatic encephalopathy
(brain
dysfunction due to liver failure
). Mild cases are self-limiting, but severe cases have a high risk of death
. Severe cases may be treated with glucocorticoids.
levels (as determined by liver function tests
). Alcoholic hepatitis can vary from mild with only liver enzyme elevation to severe liver inflammation with development of jaundice, prolonged prothrombin time
, and even liver failure. Severe cases are characterized by either obtundation (dulled consciousness) or the combination of elevated bilirubin
levels and prolonged prothrombin time; the mortality rate in both severe categories is 50% within 30 days of onset.
Alcoholic hepatitis is distinct from cirrhosis caused by long-term alcohol consumption. Alcoholic hepatitis can occur in patients with chronic alcoholic liver disease and alcoholic cirrhosis. Alcoholic hepatitis by itself does not lead to cirrhosis, but cirrhosis is more common in patients with long term alcohol consumption. Some alcoholics develop acute hepatitis as an inflammatory reaction to the cells affected by fatty change
. This is not directly related to the dose of alcohol. Some people seem more prone to this reaction than others. This is called alcoholic steatonecrosis
and the inflammation probably predisposes to liver fibrosis
.
If chronic liver disease is also present:
recommend corticosteroids. Patients should be risk stratified using a MELD Score
or Child-Pugh score
.
40 mg daily for four weeks followed by a taper.
found that among patients with a discriminant function score > 32 and at least one of the following symptoms (palpable tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit), 4.6 patients must be treated
with pentoxifylline 400 mg orally 3 times daily for 4 weeks to prevent one patient from dying.
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
(inflammation of the liver) due to excessive intake of alcohol
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
. While distinct from cirrhosis
Cirrhosis
Cirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
, it is regarded as the earliest stage of alcoholic liver disease
Alcoholic liver disease
Alcoholic liver disease is a term that encompasses the hepatic manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with hepatic fibrosis or cirrhosis. It is the major cause of liver disease in Western countries...
. Symptoms are jaundice
Jaundice
Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
, ascites
Ascites
Ascites is a gastroenterological term for an accumulation of fluid in the peritoneal cavity.The medical condition is also known as peritoneal cavity fluid, peritoneal fluid excess, hydroperitoneum or more archaically as abdominal dropsy. Although most commonly due to cirrhosis and severe liver...
(fluid accumulation in the abdominal cavity
Abdominal cavity
The abdominal cavity is the body cavity of the human body that holds the bulk of the viscera. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shaped roof is the thoracic diaphragm , and its oblique floor is the pelvic inlet...
), fatigue and hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy is the occurrence of confusion, altered level of consciousness and coma as a result of liver failure. In the advanced stages it is called hepatic coma or coma hepaticum...
(brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
dysfunction due to liver failure
Liver failure
Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease , and indicates that the liver has sustained severe damage . The complications are hepatic encephalopathy and impaired protein synthesis...
). Mild cases are self-limiting, but severe cases have a high risk of death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
. Severe cases may be treated with glucocorticoids.
Symptoms and signs
Alcoholic hepatitis is characterized by a variable constellation of symptoms, which may include feeling unwell, enlargement of the liver, development of fluid in the abdomen (ascites), and modest elevation of liver enzymeEnzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
levels (as determined by liver function tests
Liver function tests
Liver function tests , are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. The parameters measured include PT/INR, aPTT, albumin, billirubin and others...
). Alcoholic hepatitis can vary from mild with only liver enzyme elevation to severe liver inflammation with development of jaundice, prolonged prothrombin time
Prothrombin time
The prothrombin time and its derived measures of prothrombin ratio and international normalized ratio are measures of the extrinsic pathway of coagulation. This test is also called "ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the measure of warfarin...
, and even liver failure. Severe cases are characterized by either obtundation (dulled consciousness) or the combination of elevated bilirubin
Bilirubin
Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
levels and prolonged prothrombin time; the mortality rate in both severe categories is 50% within 30 days of onset.
Alcoholic hepatitis is distinct from cirrhosis caused by long-term alcohol consumption. Alcoholic hepatitis can occur in patients with chronic alcoholic liver disease and alcoholic cirrhosis. Alcoholic hepatitis by itself does not lead to cirrhosis, but cirrhosis is more common in patients with long term alcohol consumption. Some alcoholics develop acute hepatitis as an inflammatory reaction to the cells affected by fatty change
Steatosis
In cellular pathology, steatosis is the process describing the abnormal retention of lipids within a cell. It reflects an impairment of the normal processes of synthesis and elimination of triglyceride fat. Excess lipid accumulates in vesicles that displace the cytoplasm...
. This is not directly related to the dose of alcohol. Some people seem more prone to this reaction than others. This is called alcoholic steatonecrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
and the inflammation probably predisposes to liver fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
.
Diagnosis
The ratio of aspartate aminotransferase to alanine aminotransferase is usually 2 or more. In most cases, the liver enzymes do not exceed 500.Pathophysiology
Some signs and pathological changes in liver histology include:- Mallory's hyalineMallory bodyIn histopathology, a Mallory body, Mallory-Denk body, and Mallory's hyaline, is an inclusion found in the cytoplasm of liver cells.-Associated conditions:...
- a condition where pre-keratin filaments accumulate in hepatocytes. This sign is not limited to alcoholic liver disease, but is often characteristic. - Ballooning degenerationBallooning degenerationIn histopathology, ballooning degeneration, formally ballooning degeneration of hepatocytes, is a form of liver parenchymal cell death....
- hepatocytes in the setting of alcoholic change often swell up with excess fat, water and protein; normally these proteins are exported into the bloodstream. Accompanied with ballooning, there is necrotic damage. The swelling is capable of blocking nearby biliary ducts, leading to diffuse cholestasisCholestasisIn medicine, cholestasis is a condition where bile cannot flow from the liver to the duodenum. The two basic distinctions are an obstructive type of cholestasis where there is a mechanical blockage in the duct system such as can occur from a gallstone or malignancy and metabolic types of...
. - InflammationInflammationInflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
- neutrophilic invasion is triggered by the necrotic changes and presence of cellular debris within the lobules. Ordinarily the amount of debris is removed by Kupffer cells, although in the setting of inflammation they become overloaded, allowing other white cells to spill into the parenchymaParenchymaParenchyma is a term used to describe a bulk of a substance. It is used in different ways in animals and in plants.The term is New Latin, f. Greek παρέγχυμα - parenkhuma, "visceral flesh", f. παρεγχεῖν - parenkhein, "to pour in" f. para-, "beside" + en-, "in" + khein, "to pour"...
. These cells to hepatocytes with Mallory bodies.
If chronic liver disease is also present:
- FibrosisFibrosisFibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
- CirrhosisCirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
- a progressive and permanent type of fibrotic degeneration of liver tissue.
Treatment and management
Clinical practice guidelines by the American College of GastroenterologyAmerican College of Gastroenterology
The American College of Gastroenterology is a Bethesda, Maryland-based medical association of gastroenterologists.The association was founded in 1932 and holds annual meetings and regional postgraduate continuing education courses, establishes research grants, and publishes The American Journal of...
recommend corticosteroids. Patients should be risk stratified using a MELD Score
Model for End-Stage Liver Disease
The Model for End-Stage Liver Disease, or MELD, is a scoring system for assessing the severity of chronic liver disease. It was initially developed to predict death within three months of surgery in patients who had undergone a transjugular intrahepatic portosystemic shunt procedure, and was...
or Child-Pugh score
Child-Pugh score
In medicine , the Child-Pugh score is used to assess the prognosis of chronic liver disease, mainly cirrhosis...
.
Corticosteroids
Patients with a modified Maddrey's discriminant function score > 32 or hepatic encephalopathy should be considered for treatment with prednisolonePrednisolone
Prednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
40 mg daily for four weeks followed by a taper.
Pentoxifylline
A randomized controlled trialRandomized controlled trial
A randomized controlled trial is a type of scientific experiment - a form of clinical trial - most commonly used in testing the safety and efficacy or effectiveness of healthcare services or health technologies A randomized controlled trial (RCT) is a type of scientific experiment - a form of...
found that among patients with a discriminant function score > 32 and at least one of the following symptoms (palpable tender hepatomegaly, fever, leukocytosis, hepatic encephalopathy, or hepatic systolic bruit), 4.6 patients must be treated
Number needed to treat
The number needed to treat is an epidemiological measure used in assessing the effectiveness of a health-care intervention, typically a treatment with medication. The NNT is the average number of patients who need to be treated to prevent one additional bad outcome...
with pentoxifylline 400 mg orally 3 times daily for 4 weeks to prevent one patient from dying.