Liver and intrahepatic bile ducts-nontumor - Alcoholic hepatitis and alcoholic liver disease

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Liver and intrahepatic bile ducts-nontumor

Hepatitis - noninfectious

Alcoholic hepatitis and alcoholic liver disease

Reviewers: Komal Arora, M.D. (see Reviewers page)
Revised: 28 April 2012, last major update April 2012
Copyright: (c) 2004-2012, PathologyOutlines.com, Inc.

General
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● U.S. has 10 million alcoholics, 200,000 alcohol related deaths/year, 25% of hospitalized patients have problems related to alcohol abuse
● Alcohol is largest single cause of liver failure in US; damage affected by duration and quantity of consumption and patient’s genetic makeup
● 8 beers/day causes reversible fatty liver; 16 beers/day for 10 years is associated with severe injury
● Alcohol related liver disease consists of hepatic steatosis (50%), alcoholic hepatitis (20%) and cirrhosis (10%); 20% have other liver pathology, including Hepatitis C infection
● Alcoholic cirrhosis: only 10% of alcoholics develop cirrhosis
● May develop without steatosis or alcoholic hepatitis
● Resembles cirrhosis from other causes
● Women are more susceptible to hepatic injury than men
● Symptoms of alcoholic hepatitis: acute onset, usually after heavy drinking
● Variable symptoms ranging from none to acute hepatic failure; may have acute cholestatic syndrome
● 10% risk of death with each bout of hepatitis, cirrhosis in 1/3 within a few years with repeated bouts
● Hepatitis may persist and progress even with abstinence
● 5 year survival: 90% in abstainers without jaundice, ascites or hematemesis vs. 50% if continue to drink
● Death due to hepatic coma, GI bleed, infection, hepatorenal syndrome after bout of alcoholic hepatitis, hepatocellular carcinoma (3%)
● Sudden death may be due to abnormality in heart conduction system (Arch Pathol Lab Med 2001;125:21)
● Fibrosis: initially sinusoidal and perivenular; periportal fibrosis may predominate with repeated bouts of heavy alcohol intake
● Alcoholic cirrhosis: final and irreversible form of alcoholic liver disease
● Initially cirrhotic liver is yellow, fatty, enlarged (> 2 kg); eventually becomes brown, shrunken, nonfatty, < 1 kg
● Initial fibrous septa are delicate, regenerative micronodules; nodules then become larger and have hobnail appearance on hepatic surface, and bands of fibrous tissue become wider
● Laennec cirrhosis: broad expanses of tough, pale scar tissue due to ischemic necrosis and fibrous obliteration of nodules
● Also bile stasis; Mallory’s hyaline rare

Pathophysiology
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● Alcohol consumption results in translocation of gut bacteria into the portal system along with lipopolysaccharides that interact with toll-like receptors, and results in production of inflammatory and immunogenic mediators such as tumor necrosis factor-α and interferons (World J Hepatol 2011;3:114)
● Alcohol consumption causes shunting of normal substrates away from catabolism and toward lipid biosynthesis due to (a) excess NADH generation from alcohol dehydrogenase and acetaldehyde dehydrogenase, (b) impaired assembly/secretion of lipoproteins and (c) increased peripheral fat catabolism
● P450 induction causes other drugs to be transformed to toxic metabolites; free radicals, from microsomal oxidation of alcohol, damage proteins and membranes
● Alcohol directly affects microtubular and mitochondrial function, also induces immunologic attack on hepatic neoantigens
● Acetaldehyde (alcohol metabolite) causes lipid peroxidation and acetaldehyde-protein adduct formation
● Collagen deposition by perisinusoidal hepatic stellate (Ito) cells is due to Kupffer cell activation (release of TNF-alpha, IL1/6, TGF-beta), platelet-activating factor, influx of neutrophils into parenchyma
● Alcohol also causes derangements of vascular perfusion

Treatment
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● Corticosteroids and pentoxifylline (World J Hepatol 2011;3:205); alcohol abstinence

Gross description
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● Initially liver is 4-6 kg, yellow, greasy, easily fractured
● Later liver becomes red with bile-stained areas
● May contain visible nodules and fibrosis

Micro description
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● Early - hepatocyte swelling and necrosis, macrovesicular fatty change due to triglyceride in centrilobular area, Mallory’s hyaline with surrounding neutrophils
● Also portal lymphocytes (40%, even without hepatitis B/C, Hum Pathol 2002;33:1170) and macrophages
● Reversible macrovesicular steatosis occurs after moderate alcohol intake, fibrosis may develop late around central veins and extend into parenchyma (sclerosing hyaline necrosis, highlighted with trichrome stain)
● May have marked cholestatic features or giant mitochondria that appear as globular eosinophilic hyaline inclusions larger than hepatocyte nuclei

Micro images
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Macro and microsteatosis, Mallory bodies

Mallory bodies

Fat stain (osmium tetraoxide)

Electron microscopy description
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● Giant mitochondria

Differential diagnosis
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● Jejunoileal bypass, drug reactions, nonalcoholic steatohepatitis, megamitochondria (resemble Mallory’s hyaline but coarsely granular and more regular in contour, and trichrome stains them red)

Additional references
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● Clin Liver Dis 2005;9:37, N Engl J Med 2009;360:2758

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