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Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses 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
manifestations 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 ...
overconsumption, including
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 ...
,
alcoholic hepatitis 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 Jaundice, also ...

alcoholic hepatitis
, and chronic
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
with 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 ...
or
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 ...
. It is the major cause of
liver disease Liver disease (also called hepatic disease) is a type of damage to or disease A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not due to any imme ...
in Western countries. Although
steatosis Steatosis, also called fatty change, is abnormal retention of fat (lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecu ...

steatosis
(
fatty liver disease Fatty liver disease (FLD), also known as hepatic steatosis, is a condition where excess fat builds up in the liver The liver is an organ only found in vertebrates which detoxifies various metabolites, synthesizes proteins and produces bio ...
) will develop in any individual who consumes a large quantity of alcoholic beverages over a long period of time, this process is transient and reversible. More than 90% of all heavy drinkers develop fatty liver whilst about 25% develop the more severe alcoholic hepatitis, and 15% cirrhosis.


Risk factors

The risk factors presently (2010) known are: * Quantity of alcohol taken: Consumption of 60–80g per day (14g is considered one standard drink in the US, i.e., 1.5 fl oz hard liquor, 5 fl oz wine, 12 fl oz beer; drinking a six-pack of 5% ABV beer daily would be 84g and just over the upper limit) for 20 years or more in men, or 20g/day for women significantly increases the risk of hepatitis and fibrosis by 7% to 47%, * Pattern of drinking: Drinking outside of meal times increases up to 3 times the risk of alcoholic liver disease. * Sex: Women are twice as susceptible to alcohol-related liver disease, and may develop alcoholic liver disease with shorter durations and doses of chronic consumption. The lesser amount of alcohol dehydrogenase secreted in the gut, higher proportion of body fat in women, and changes in fat absorption due to the menstrual cycle may explain this phenomenon. * Hepatitis C infection: A concomitant hepatitis C infection significantly accelerates the process of liver injury. * Genetic factors: Genetic factors predispose both to alcoholism and to alcoholic liver disease. Both monozygotic twins are more likely to be alcoholics and to develop liver cirrhosis than both dizygotic twins. Polymorphisms in the enzymes involved in the metabolism of alcohol, such as ADH,
ALDH Aldehyde dehydrogenases () are a group of 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), sub ...
, CYP4502E1, mitochondrial dysfunction, and cytokine polymorphism may partly explain this genetic component. However, no specific polymorphisms have currently been firmly linked to alcoholic liver disease. *
Iron overload Iron overload or haemochromatosis (spelled ''hemochromatosis'' in American English American English (AmE, AE, AmEng, USEng, en-US), sometimes called United States English or U.S. English, is the set of varieties of the English language nat ...
(hemochromatosis) * Diet: Malnutrition, particularly vitamin A and E deficiencies, can worsen alcohol-induced liver damage by preventing regeneration of hepatocytes. This is particularly a concern as alcoholics are usually malnourished because of a poor diet, anorexia, and encephalopathy.


Pathophysiology

The mechanism of ALD is not completely understood. 80% of alcohol passes through the liver to be detoxified. Chronic consumption of alcohol results in the secretion of pro-inflammatory
cytokine Cytokines are a broad and loose category of small 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 ...

cytokine
s (
TNF-alpha Tumor necrosis factor (TNF, cachexin, or cachectin; often called tumor necrosis factor alpha or TNF-α) is an adipokine The adipokines, or adipocytokines (Greek ''adipo-'', fat; ''cytos-'', cell; and ''-kinos'', movement) are cytokines (cell si ...

TNF-alpha
,
Interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...
and
Interleukin 8 Interleukin 8 (IL-8 or chemokine (C-X-C motif) ligand 8, CXCL8) is a chemokine Chemokines (Greek ''-kinos'', movement) are a family of small cytokines, or signaling protein Proteins are large biomolecules or macromolecules that are comprised ...
,
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species Reactive oxygen species (ROS) are highly chemicals formed from O2. Examples of ROS include s, , , , and . The reduction of molecular oxygen ...
,
lipid peroxidation Lipid peroxidation is the chain of reactions of oxidative (mild reducing agent) are added to powdered potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4 and composed of potassium ion, K+ and ...

lipid peroxidation
, and
acetaldehyde Ethanal (common name acetaldehyde) is an organic chemical compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds ...
toxicity Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacteria, bacterium, or plant, as well as the effect on ...

toxicity
. These factors cause
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 ...
,
apoptosis Apoptosis (from Ancient Greek Ancient Greek includes the forms of the Greek language Greek ( el, label=Modern Greek Modern Greek (, , or , ''Kiní Neoellinikí Glóssa''), generally referred to by speakers simply as Greek (, ) ...

apoptosis
and eventually
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 ...
of liver cells. Why this occurs in only a few individuals is still unclear. Additionally, the liver has tremendous capacity to regenerate and even when 75% of
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 ...
are dead, it continues to function as normal.


Fatty change

Fatty change, or
steatosis Steatosis, also called fatty change, is abnormal retention of fat (lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecu ...

steatosis
, is the accumulation of fatty acids in
liver cells 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, th ...
. These can be seen as fatty globules under the microscope. Alcoholism causes development of large fatty globules (
macro Macro (or MACRO) may refer to: Science and technology * Macroscopic The macroscopic scale is the length scale on which objects or phenomena are large enough to be visible with the naked eye, without magnifying optical instruments. It is the o ...
- vesicular steatosis) throughout the liver and can begin to occur after a few days of heavy drinking. Alcohol is metabolized by
alcohol dehydrogenase Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to NADH. ...

alcohol dehydrogenase
() into
acetaldehyde Ethanal (common name acetaldehyde) is an organic chemical compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds ...
, then further metabolized by
aldehyde dehydrogenase Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have bee ...
(ALDH) into
acetic acid Acetic acid , systematically named ethanoic acid , is a colourless liquid organic compound with the chemical formula CH3COOH (also written as CH3CO2H, C2H4O2, or HC2H3O2). Vinegar is no less than 4% acetic acid by volume, making acetic acid ...

acetic acid
, which is finally oxidized into
carbon dioxide Carbon dioxide (chemical formula A chemical formula is a way of presenting information about the chemical proportions of s that constitute a particular or molecule, using symbols, numbers, and sometimes also other symbols, such as pare ...

carbon dioxide
() and water (). This process generates
NADH Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphate ...
, and increases the NADH/
NAD+ Nicotinamide adenine dinucleotide (NAD) is a Cofactor (biochemistry), coenzyme central to metabolism. Found in all living cell (biology), cells, NAD is called a dinucleotide because it consists of two nucleotides joined through their phosphat ...

NAD+
ratio. A higher NADH concentration induces
fatty acid synthesis Fatty acid synthesis is the creation of fatty acid fatty acids have perfectly straight chain structure. Unsaturated ones are typically bent, unless they have a trans configuration. In chemistry Chemistry is the scientific discipline invo ...
while a decreased NAD level results in decreased fatty acid oxidation. Subsequently, the higher levels of fatty acids signal the liver cells to compound it to
glycerol Glycerol (; also called glycerine in British English and glycerin in American English) is a simple polyol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
to form
triglyceride A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester An ester is a derived from an (organic or inorganic) in which at least one –OH group is replaced by an –O– () group, as in the substitution reaction of a an ...

triglyceride
s. These triglycerides accumulate, resulting in fatty liver.


Alcoholic hepatitis

Alcoholic hepatitis is characterized by the inflammation of hepatocytes. Between 10% and 35% of heavy drinkers develop alcoholic hepatitis (NIAAA, 1993). While development of hepatitis is not directly related to the dose of alcohol, some people seem more prone to this reaction than others. This is called alcoholic steato-
necrosis Necrosis (from Ancient Greek wikt:νέκρωσις, νέκρωσις ''nékrōsis'' 'death') is a form of cell injury which results in the premature death of Cell (biology), cells in living Tissue (biology), tissue by Autolysis (biology), autol ...
and the inflammation appears to predispose 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 ...
. Inflammatory cytokines (TNF-alpha, IL6 and IL8) are thought to be essential in the initiation and perpetuation of liver injury and cytotoxic hepatomegaly by inducing apoptosis and severe hepatotoxicity. One possible mechanism for the increased activity of TNF-α is the increased intestinal permeability due to liver disease. This facilitates the absorption of the gut-produced endotoxin into the portal circulation. The Kupffer cells of the liver then phagocytose endotoxin, stimulating the release of TNF-α. TNF-α then triggers apoptotic pathways through the activation of caspases, resulting in cell death.


Cirrhosis

Cirrhosis is a late stage of serious liver disease marked by
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 ...
(swelling),
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 ...
(cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and
necrosis Necrosis (from Ancient Greek wikt:νέκρωσις, νέκρωσις ''nékrōsis'' 'death') is a form of cell injury which results in the premature death of Cell (biology), cells in living Tissue (biology), tissue by Autolysis (biology), autol ...
(cell death). Between 10% to 20% of heavy drinkers will develop cirrhosis of the liver (NIAAA, 1993).
Acetaldehyde Ethanal (common name acetaldehyde) is an organic chemical compound , CH4; is among the simplest organic compounds. In chemistry Chemistry is the scientific discipline involved with Chemical element, elements and chemical compound, compounds ...
may be responsible for alcohol-induced fibrosis by stimulating
collagen Collagen () is the main structural 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 Cowder ...

collagen
deposition by
hepatic stellate cell Hepatic stellate cells (HSC), also known as perisinusoidal cells or Ito cells (earlier ''lipocytes'' or ''fat-storing cells''), are pericyte Pericytes (previously known as Rouget cells) are multi-functional mural cells of the microcirculation t ...
s. The production of oxidants derived from NADPH oxi- dase and/or
cytochrome Image:Cytochrome c.png, 250px, Cytochrome ''c'' with heme ''c''. Cytochromes are redox-active proteins containing a heme, with a central Fe atom at its core, as a Cofactor (biochemistry), cofactor. They are involved in electron transport chain and ...
P-450 2E1 and the formation of acetaldehyde-protein adducts damage the
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane A biological membrane, biomembrane or cell membrane is a selectively permeable membra ...

cell membrane
.
Symptom Signs and symptoms are the observed or detectable signs, and experienced symptoms of an illness, injury, or condition. A sign for example may be a higher or lower temperature than normal, raised or lowered blood pressure or an abnormality show ...
s 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), liver enlargement, and pain and tenderness from the structural changes in damaged liver architecture. Without total abstinence from alcohol use, cirrhosis will eventually lead 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 ...
. Late complications of cirrhosis or liver failure include
portal hypertension Portal hypertension is abnormally increased portal venous pressure – blood pressure in the portal vein and its branches, that drain from most of the intestine to the liver. Portal hypertension is defined as a hepatic venous pressure gradient grea ...
(high
blood pressure Blood pressure (BP) is the pressure Pressure (symbol: ''p'' or ''P'') is the force In physics Physics is the natural science that studies matter, its Elementary particle, fundamental constituents, its Motion (physics), motio ...

blood pressure
in the
portal vein The portal vein or hepatic portal vein (HPV) is a blood vessel The blood vessels are the components of the circulatory system The circulatory system, also called the cardiovascular system or the vascular system, is an organ system that ...
due to the increased flow resistance through the damaged liver), coagulation disorders (due to impaired production of coagulation factors),
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 ...
(heavy abdominal swelling due to buildup of fluids in the tissues) and other complications, including
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 ...
and the
hepatorenal syndrome Hepatorenal syndrome (often abbreviated HRS) is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transpl ...
. Cirrhosis can also result from other causes than hazardous alcohol use, such as
viral hepatitis Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic v ...
and heavy exposure to
toxin A toxin is a harmful substance produced within living cells or organisms; synthetic toxicants created by artificial processes are thus excluded. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived from the word toxic ...
s other than
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 ...

alcohol
. The late stages of cirrhosis may look similar medically, regardless of cause. This phenomenon is termed the "final common pathway" for the disease. Fatty change and alcoholic hepatitis with
abstinence Abstinence is a self-enforced restraint from indulging in bodily activities that are widely experienced as giving pleasure Pleasure refers to experience that feels good, that involves the enjoyment of something. It contrasts with pain or suffe ...
can be reversible. The later stages of fibrosis and cirrhosis tend to be irreversible, but can usually be contained with abstinence for long periods of time.


Diagnosis

In the early stages, patients with ALD exhibit subtle and often no abnormal physical findings. It is usually not until development of advanced liver disease that stigmata of chronic liver disease become apparent. Early ALD is usually discovered during routine health examinations when liver enzyme levels are found to be elevated. These usually reflect alcoholic hepatic steatosis. Microvesicular and macrovesicular steatosis with inflammation are seen in liver biopsy specimens. These histologic features of ALD are indistinguishable from those of nonalcoholic fatty liver disease. Steatosis usually resolves after discontinuation of alcohol use. Continuation of alcohol use will result in a higher risk of progression of liver disease and cirrhosis. In patients with acute alcoholic hepatitis, clinical manifestations include fever, jaundice,
hepatomegaly Hepatomegaly is the condition of having an enlarged 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 ma ...
, and possible hepatic decompensation with hepatic encephalopathy, variceal bleeding, and ascites accumulation. Tender hepatomegaly may be present, but abdominal pain is unusual. Occasionally, the patient may be asymptomatic.


Laboratory findings

In people with alcoholic hepatitis, the serum
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
(AST) 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 ...
(ALT) ratio is greater than 2:1. AST and ALT levels are almost always less than 500. The elevated AST to ALT ratio is due to deficiency of
pyridoxal phosphate Pyridoxal phosphate (PLP, pyridoxal Pyridoxal is one form of vitamin B6. Some medically relevant bacteria, such as those in the genera ''Granulicatella'' and ''Abiotrophia'', require pyridoxal for growth. This nutritional requirement can lead ...

pyridoxal phosphate
, which is required in the ALT enzyme synthetic pathway. Furthermore, alcohol metabolite–induced injury of hepatic
mitochondria A mitochondrion (; ) is a double-membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Biological membranes include cell membranes ...

mitochondria
results in AST isoenzyme release. Other laboratory findings include red blood cell (
mean corpuscular volume The mean corpuscular volume, or mean cell volume (MCV), is a measure of the average volume of a red blood corpuscle (or red blood cell). The measure is obtained by multiplying a volume of blood by the proportion of blood that is cellular (the hem ...
> 100) and elevations of serum gamma-glutamyl transferase (GGT),
alkaline phosphatase Alkaline phosphatase (ALP, ALKP, ALPase, Alk Phos) (), or basic phosphatase, is a homodimeric protein enzyme of 86 kilodaltons. Each monomer contains five cysteine residues, two zinc atoms and one magnesium atom crucial to its catalytic function, ...

alkaline phosphatase
, and
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
levels.
Folate Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
level is reduced in alcoholic patients due to decreased intestinal absorption, increased bone marrow requirement for folate in the presence of alcohol, and increased urinary loss. The magnitude of
leukocytosis Leukocytosis is a condition in which the white cell (leukocyte White blood cells, also called leukocytes or leucocytes, are the of the that are involved in protecting the body against both and foreign invaders. All white blood cells are p ...
(
white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the cells of the immune system The immune system is a network of biological processes that protects an organism In biology, an organism (from Ancient Greek, Greek: ...
depletion) reflects severity of liver injury. Histologic features include Mallory bodies, giant mitochondria, hepatocyte
necrosis Necrosis (from Ancient Greek wikt:νέκρωσις, νέκρωσις ''nékrōsis'' 'death') is a form of cell injury which results in the premature death of Cell (biology), cells in living Tissue (biology), tissue by Autolysis (biology), autol ...
, and
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
infiltration in the area around the veins. Mallory bodies, which are also present in other liver diseases, are condensations of cytokeratin components in the hepatocyte cytoplasm and do not contribute to liver injury. Up to 70% of patients with moderate to severe alcoholic hepatitis already have cirrhosis identifiable on biopsy examination at the time of diagnosis.


Treatment

Not drinking further alcohol is the most important part of treatment. People with chronic HCV infection should abstain from any alcohol intake, due to the risk for rapid acceleration of liver disease.


Medications

A 2006 Cochrane review did not find evidence sufficient for the use of androgenic anabolic steroids. Corticosteroids are sometimes used; however, this is recommended only when severe liver inflammation is present.
Silymarin Silibinin (International Nonproprietary Name, INN), also known as silybin (both from ''Silybum'', the Genus–differentia definition, generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardiz ...

Silymarin
has been investigated as a possible treatment, with ambiguous results. One review claimed benefit for
S-adenosyl methionine ''S''-Adenosyl methionine (SAM-e) is a common cosubstrate involved in methyl group A methyl group is an alkyl derived from methane, containing one carbon atom chemical bond, bonded to three hydrogen atoms — CH3. In chemical fo ...

S-adenosyl methionine
in disease models. The effects of anti-tumor necrosis factor medications such as
infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases An autoimmune disease is a condition arising from an abnormal immune response to a func ...
and
etanercept Etanercept, sold under the brand name Enbrel among others, is a biologic medical product A biopharmaceutical, also known as a biologic(al) medical product, or biologic, is any pharmaceutical drug A medication (also called medicament, med ...

etanercept
are unclear and possibly harmful. Evidence is unclear for
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
.
Propylthiouracil Propylthiouracil (PTU) is a medication used to treat hyperthyroidism. This includes hyperthyroidism due to Graves' disease and toxic multinodular goiter. In a thyrotoxic crisis it is generally more effective than methimazole. Otherwise it is ty ...

Propylthiouracil
may result in harm. Evidence does not support supplemental nutrition in liver disease.


Transplantation

Although in rare cases liver cirrhosis is reversible, the disease process remains mostly irreversible. Liver transplantation remains the only definitive therapy. Today, survival after liver transplantation is similar for people with ALD and non-ALD. The requirements for transplant listing are the same as those for other types of liver disease, except for a 6-month sobriety prerequisite along with psychiatric evaluation and rehabilitation assistance. Specific requirements vary among the transplant centers. Relapse to alcohol use after transplant listing results in delisting. Re-listing is possible in many institutions, but only after 3–6 months of sobriety. There are limited data on transplant survival in patients transplanted for acute alcoholic hepatitis, but it is believed to be similar to that in nonacute ALD, non-ALD, and alcoholic hepatitis with MDF less than 32.


Prognosis

The prognosis for people with ALD depends on the liver histology as well as cofactors, such as concomitant chronic viral hepatitis. Among patients with alcoholic hepatitis, progression to liver cirrhosis occurs at 10–20% per year, and 70% will eventually develop cirrhosis. Despite cessation of alcohol use, only 10% will have normalization of histology and serum liver enzyme levels. As previously noted, the MDF has been used to predict short-term mortality (i.e., MDF ≥ 32 associated with spontaneous survival of 50–65% without corticosteroid therapy, and MDF < 32 associated with spontaneous survival of 90%). The Model for End-Stage Liver Disease (MELD) score has also been found to have similar predictive accuracy in 30-day (MELD > 11) and 90-day (MELD > 21) mortality. Liver cirrhosis develops in 6–14% of those who consume more than 60–80 g of alcohol daily for men and more than 20 g daily for women. Even in those who drink more than 120 g daily, only 13.5% will suffer serious alcohol-related liver injury. Nevertheless, alcohol-related mortality was the third leading cause of death in 2003 in the United States. Worldwide mortality is estimated to be 150,000 per year.


References


Further reading

*


External links

{{DEFAULTSORT:Alcoholic Liver Disease Alcohol and health Anatomical pathology Diseases of liver
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 ...
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