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Alcoholic hepatitis is
hepatitis Hepatitis is inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogen In biology Biology is the natural science that studies life and living or ...

hepatitis
(inflammation of the
liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's t ...

liver
) due to excessive intake of
alcohol In chemistry, alcohol is an organic compound that carries at least one hydroxyl functional group (−OH) bound to a Saturated and unsaturated compounds, saturated carbon atom. The term alcohol originally referred to the primary alcohol ethan ...
. Patients typically have a history of decades 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 In nutrition Nutrition is the biochemical Biochemistry or biological chemistry, is the study of chemical processes within and relating t ...
, 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 The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces bio ...
, 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 Fibrosis, also known as fibrotic scarring, is a pathological woun ...
. 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 Jaundice, also known as icterus, is a yellowish or greenish pigmentation of the skin Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and s ...

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, abd ...
(fluid accumulation in the
abdominal cavity The abdominal cavity is a large body cavity in humans and many other animals that contains many Organ (anatomy), organs. It is a part of the abdominopelvic cavity. It is located below the thoracic cavity, and above the pelvic cavity. Its dome-shape ...

abdominal cavity
),
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
and
hepatic encephalopathy Hepatic encephalopathy (HE) is an altered level of consciousness Altered may refer to: * ''Altered'' (film), a 2006 film * Altered (drag racing), a former drag racing class *Altered scale In jazz Jazz is a music genre that originated in t ...
(
brain A brain is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tis ...

brain
dysfunction due to
liver failure Liver failure is the inability of the liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with similar functions. Plant life and animal life rely on many organs tha ...
). Mild cases are self-limiting, but severe cases have a high risk of
death Death is the permanent, irreversible cessation of all biological functions that sustain a living Living or The Living may refer to: Common meanings *Life, a condition that distinguishes organisms from inorganic objects and dead organi ...

death
. 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 vertebra ...
.


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 (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates in ...

enzyme
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 Altered may refer to: * ''Altered'' (film), a 2006 film * Altered (drag racing), a former drag racing class *Altered scale In jazz Jazz is a music genre that originated in t ...
(brain dysfunction due to liver failure causing symptoms such as confusion, decreased levels of consciousness, or
asterixis Asterixis is a tremor A tremor is an involuntary, somewhat rhythmic, muscle contraction Muscle contraction is the activation of tension Tension may refer to: Science * Psychological stress * Tension (physics), a force related to the stretchin ...
, (a characteristic jerking of the limbs)). 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 A head injury is any injury that resul ...
(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
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 Fibrosis, also known as fibrotic scarring, is a pathological woun ...
. 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 diseas ...

fatty change
. 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. T ...
and the inflammation probably predisposes to liver
fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing Wound healing refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue. In undamaged skin, the epidermis The epidermis is the ...
by activating
hepatic stellate cells The liver is an Organ (anatomy), organ only found in vertebrates which detoxification, detoxifies various metabolites, Protein biosynthesis, synthesizes proteins and produces biochemicals necessary for digestion and growth. In humans, it is locat ...
to produce collagen.


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 parenchyma Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology Zoology ()The pronunciation of zoology as is typically regarded as nonstandard, tho ...
. This sign is not limited to alcoholic liver disease, but is often characteristic. * Ballooning degeneration – hepatocytes in the setting of alcoholic change often swell up with excess fat, water and
protein Proteins are large biomolecule , showing alpha helices, represented by ribbons. This poten was the first to have its suckture solved by X-ray crystallography by Max Perutz and Sir John Cowdery Kendrew in 1958, for which they received a No ...

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
cholestasis Cholestasis is a condition where bile Bile (from latin ''bilis''), or gall, is a dark-green-to-yellowish-brown fluid produced by the of most s that aids the of s in the . In humans, bile is produced continuously by the liver (liver bile) and ...
. *
Inflammation Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogen In biology Biology is the natural science that studies life and living organisms, including their anato ...
neutrophil Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocyte Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. They are also called po ...

neutrophil
ic invasion is triggered by the necrotic changes and presence of cellular debris within the
lobules In anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecul ...
. 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 liver The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces bi ...
, although in the setting of inflammation they become overloaded, allowing other white cells to spill into the
parenchyma Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the Ancient G ...

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 permane ...
*
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 Fibrosis, also known as fibrotic scarring, is a pathological wo ...
– a progressive and permanent type of fibrotic degeneration of liver tissue.


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
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 ...
, including elevated
bilirubin Bilirubin (BR) is a yellow compound that occurs in the normal catabolic Catabolism () is the set of metabolic pathways that breaks down molecule File:Pentacene on Ni(111) STM.jpg, A scanning tunneling microscopy image of pentacene molecule ...

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 Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate In chemistry ...

aspartate aminotransferase
to
alanine aminotransferase Alanine transaminase (ALT) is a transaminase Transaminases or aminotransferases are enzyme Enzymes () are proteins that act as biological catalysts (biocatalysts). Catalysts accelerate chemical reactions. The molecules upon which enzymes m ...
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 suffering from alcoholic hepatitis, and it negatively affects their outcomes. Improved nutrition has been shown to improve liver function and reduce incidences encephalopathy and infections. *
Corticosteroids Corticosteroids are a class of steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is shown with IUPAC The International Union of Pure a ...
: These guidelines suggest that patients with a modified Maddrey's discriminant function score > 32 or hepatic encephalopathy should be considered for treatment with
prednisolone Prednisolone is a corticosteroid, steroid medication used to treat certain types of allergies, inflammation, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, hypercalcemi ...

prednisolone
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 Pentoxifylline, also known as oxpentifylline, is a xanthine derivative used as a drug to treat muscle pain in people with peripheral artery disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply ...

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 : When used in conjunction with corticosteroids, improves survival at 28 days by decreasing rates of infection and hepatorenal syndrome. *
Liver Transplantation Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver The liver is an organ Organ may refer to: Biology * Organ (anatomy) An organ is a group of Tissue (biology), tissues with ...
: Early liver transplantation is ideal and helps to save lives. However, patients must remain abstinent from alcohol for 6 months prior to transplantation, but the ethics and science behind this are controversial.


See also

*
AST/ALT ratio The AST/ALT ratio is the ratio between the concentrations of the enzymes aspartate transaminase (AST) and alanine transaminase, alanine transaminase, aka alanine aminotransferase (ALT) in the blood of a human or animal. It is measured with a blood t ...
* Lille Model *
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. T ...


References


External links

{{DEFAULTSORT:Alcoholic Hepatitis Alcohol and health Hepatitis Inflammations