Alcoholic hepatitis is

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...

(inflammation of the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

) due to excessive intake of alcohol. Patients typically have a history of at least 10 years of heavy alcohol intake, typically 8-10 drinks per day. It is usually found in association with

fatty liver Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complicat ...

, an early stage of

alcoholic liver disease Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis ...

, and may contribute to the progression of fibrosis, leading to

cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

. Symptoms may present acutely after a large amount of alcoholic intake in a short time period, or after years of excess alcohol intake. Signs and symptoms of alcoholic hepatitis include jaundice (yellowing of the skin and eyes),

ascites Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, a ...

(fluid accumulation in the abdominal cavity), fatigue and

hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stage ...

(

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

dysfunction due to liver failure). Mild cases are self-limiting, but severe cases have a high risk of

death Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...

. Severe cases may be treated with

glucocorticoids Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...

. The condition often comes on suddenly and may progress in severity very rapidly.

Signs and symptoms

Alcoholic hepatitis is characterized by a number of symptoms, which may include feeling unwell, enlargement of the liver, development of fluid in the abdomen (ascites), and modest elevation of liver

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

levels (as determined by

liver function tests Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin ti ...

). May also present with

Hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness as a result of liver failure. Its onset may be gradual or sudden. Other symptoms may include movement problems, changes in mood, or changes in personality. In the advanced stage ...

(brain dysfunction due to liver failure) causing symptoms such as confusion, decreased levels of consciousness, or asterixis, (a characteristic flapping movement when the wrist is extended indicative of hepatic encephalopathy). Severe cases are characterized by profound jaundice,

obtundation Obtundation refers to less than full alertness (altered level of consciousness), typically as a result of a medical condition or trauma. There is a huge range of potential causes including head injury, interruption of blood circulation, impaired ...

(ranging from drowsiness to unconsciousness), and progressive critical illness; the mortality rate is 50% within 30 days of onset despite best care. 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

. 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, also called fatty change, is abnormal retention of fat (lipids) within a cell or organ. Steatosis most often affects the liver – the primary organ of lipid metabolism – where the condition is commonly referred to as fatty liver disea ...

. This is not directly related to the dose of alcohol. Some people seem more prone to this reaction than others. This inflammatory reaction to the fatty change is called alcoholic

steatohepatitis Steatohepatitis is a type of fatty liver disease, characterized by inflammation of the liver with concurrent fat accumulation in liver. Mere deposition of fat in the liver is termed steatosis, and together these constitute fatty liver changes. ...

and the inflammation probably predisposes to liver

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

by activating

hepatic stellate cells The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...

to produce collagen. Depiction_of_a_liver_failure_patient

Pathophysiology

Some signs and pathological changes in liver histology include: * Mallory's hyaline body – a condition where pre-keratin filaments accumulate in

hepatocytes A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

. This sign is not limited to alcoholic liver disease, but is often characteristic. *

Ballooning degeneration In histopathology, ballooning degeneration, formally ballooning degeneration of hepatocytes, is a form of liver parenchymal cell (i.e. hepatocyte) death. The name is derived from the fact that the cells undergoing this form of cell death incr ...

– hepatocytes in the setting of alcoholic change often swell up with excess fat, water and

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

; 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

cholestasis 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 that can occur from a gallstone or malig ...

. *

Inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molec ...

–

neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...

ic invasion is triggered by the necrotic changes and presence of cellular debris within the

lobules In anatomy, a lobe is a clear anatomical division or extension of an organ (as seen for example in the brain, lung, liver, or kidney) that can be determined without the use of a microscope at the gross anatomy level. This is in contrast to the m ...

. Ordinarily the amount of debris is removed by

Kupffer cells Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. Ku ...

, although in the setting of inflammation they become overloaded, allowing other white cells to spill into the parenchyma. These cells are particularly attracted to hepatocytes with Mallory bodies. If chronic liver disease is also present: *

Fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

Cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue rep ...

– a progressive and permanent type of fibrotic degeneration of liver tissue. Pathogenesis_alcoholic_liver_injury

Epidemiology

* Alcoholic hepatitis occurs in approximately 1/3 of chronic alcohol drinkers. * 10-20% of patients with alcoholic hepatitis progress to alcoholic liver cirrhosis every year. * Patients with liver cirrhosis develop liver cancer at a rate of 1.5% per year. * In total, 70% of those with alcoholic hepatitis will go on to develop alcoholic liver cirrhosis in their lifetimes. *Infection risk is elevated in patients with alcoholic hepatitis (12-26%). It increases even higher with use of corticosteroids (50%) when compared with the general population. *Untreated alcoholic hepatitis mortality in one month of presentation may be as high as 40-50%.

Diagnosis

The diagnosis is made in a patient with history of significant alcohol intake who develops worsening

, including elevated bilirubin (typically greater than 3.0) and aminotransferases, and onset of jaundice within the last 8 weeks. The ratio of

aspartate aminotransferase Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase (GOT, SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme () that was first described by Arthur ...

alanine aminotransferase Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first character ...

is usually 2 or more. In most cases, the liver enzymes do not exceed 500. Liver biopsy confirms the diagnosis.

Management

Clinical practice guidelines have recommended corticosteroids. People should be risk stratified using a MELD Score or Child-Pugh score. These scores are used to evaluate the severity of the liver disease based on several lab values. The greater the score, the more severe the disease. *Abstinence: Stopping further alcohol consumption is the number one factor for recovery in patients with alcoholic hepatitis. *Nutrition Supplementation: Protein and calorie deficiencies are seen frequently in patients with alcoholic hepatitis, and it negatively affects their outcomes. Improved nutrition has been shown to improve liver function and reduce incidences encephalopathy and infections. * Corticosteroids: These guidelines suggest that patients with a

modified Maddrey's discriminant function Maddrey's discriminant function (DF) is the traditional model for evaluating the severity and prognosis in alcoholic hepatitis and evaluates the efficacy of using alcoholic hepatitis steroid treatment. The Maddrey DF score is a predictive statisti ...

score > 32 or hepatic encephalopathy should be considered for treatment with

prednisolone Prednisolone is a steroid medication used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthr ...

40 mg daily for four weeks followed by a taper. Models such as the Lille Model can be used to monitor for improvement or to consider alternative treatment. * Pentoxifylline: Systematic reviews comparing the treatment of pentoxifylline with corticosteroids show there is no benefit to treatment with pentoxifylline Potential for combined therapy: A large prospective study of over 1000 patients investigated whether prednisolone and pentoxifylline produced benefits when used alone or in combination. Pentoxifylline did not improve survival alone or in combination. Prednisolone gave a small reduction in mortality at 28 days but this did not reach significance, and there were no improvements in outcomes at 90 days or 1 year. *IV

N-acetylcysteine Acetylcysteine, also known as ''N''-acetylcysteine (NAC), is a medication that is used to treat paracetamol overdose and to loosen thick mucus in individuals with chronic bronchopulmonary disorders like pneumonia and bronchitis. It has been used ...

: When used in conjunction with corticosteroids, improves survival at 28 days by decreasing rates of infection and hepatorenal syndrome. * Liver Transplantation: Early liver transplantation is ideal and helps to save lives. However, most transplant providers in the

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...

require a period of alcohol abstinence (typically 6 months) prior to transplant, but the ethics and science behind this are controversial.

References

External links

{{DEFAULTSORT:Alcoholic Hepatitis Alcohol and health Hepatitis Inflammations