ALCOHOLIC LIVER DISEASE
Alcohol is a well-known cause of fatty liver disease in adults, and can manifest histologically as
steatosis, steatohepatitis, and cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) can mimic the entire spectrum of hepatic changes
typically associated with alcohol abuse and is associated with insulin resistance, obesity,
diabetes mellitus, hypertension, and dyslipidemias, collectively called the metabolic syndrome.
The morphologic changes of alcoholic and nonalcoholic fatty liver disease are indistinguishable,
they are described together:
Three categories of liver alterations are observed in fatty liver disease.
They can be present in any combination:
A. Steatosis (fatty change)
B. Hepatitis (alcoholic or steatohepatitis)
C. Fibrosis.
All changes in alcoholic liver disease begin in acinus zone 3 and extend outward toward the
portal tracts with increasing severity of injury.
1. Hepatic Steatosis (Fatty Liver).
Fat accumulation typically begins in centrilobular hepatocytes zone 3.
As steatosis progresses fat accumulation spread from central vein to periportal regions.
Soft yellow greasy liver.
Fatty change is completely reversible if there is abstention from further intake of alcohol.
2. Alcoholic (Steato-) Hepatitis. Alcoholic hepatitis is characterized by:
A. Hepatocyte swelling and necrosis:
Foci of cells undergo swelling (ballooning) and necrosis.
Swelling results from the accumulation of fat and water.
B. Mallory-Denk bodies:
Eosinophilic material in ballooned hepatocytes.
tangled threads of intermediate filaments such as keratins 8 and 18 in complex with
other proteins such as ubiquitin.
, These inclusions are a characteristic but not specific feature of alcoholic liver disease
since they are also present in NAFLD, Wilson disease and in chronic biliary tract
diseases.
C. Neutrophilic reaction:
Accumulate around degenerating hepatocytes, particularly those having Mallory-Denk
bodies.
3. Alcoholic Steatofibrosis.
Activation of sinusoidal stellate cells and portal fibroblasts, giving rise to fibrosis.
Fibrosis first appears in centrilobular region as central vein sclerosis and spreading outwards
encircling individual or small clusters of hepatocytes in a chicken wire fence pattern.
These webs of scar eventually link to portal tracts and then begin to condense into central-
portal fibrous septa.
With developing nodularity, cirrhosis becomes established.
Established nodules by new webs of, perisinusoidal scarring leads to a classic micronodular
or Laennec cirrhosis first described for end-stage alcoholic liver disease.
RISK FACTORS
Gender. Women seem to be more susceptible to hepatic injury than men, although the majority
of patients are men. estrogen increases gut permeability to endotoxins.
Ethnic and genetic differences. In the United States, cirrhosis rates are higher for African
American drinkers than for white Americans drinker.
Genetic polymorphisms in detoxifying enzymes ALDH2.
Comorbid conditions. Iron overload and infections with HCV and HBV synergize with alcohol,
leading to increased severity of liver disease.
Exposure to alcohol causes steatosis, dysfunction of mitochondrial and cellular membranes,
hypoxia, and oxidative stress.
Hepatocellular steatosis results from
(1) shunting of normal substrates away from catabolism and toward lipid biosynthesis, as a
result of increased generation of reduced nicotinamide adenine dinucleotide (NADH) by the two
major enzymes of alcohol metabolism, alcohol dehydrogenase and acetaldehyde
dehydrogenase.
(2) impaired assembly and secretion of lipoproteins.
(3) increased peripheral catabolism of fat, thus releasing free fatty acids into the circulation.
Alcohol is a well-known cause of fatty liver disease in adults, and can manifest histologically as
steatosis, steatohepatitis, and cirrhosis.
Nonalcoholic fatty liver disease (NAFLD) can mimic the entire spectrum of hepatic changes
typically associated with alcohol abuse and is associated with insulin resistance, obesity,
diabetes mellitus, hypertension, and dyslipidemias, collectively called the metabolic syndrome.
The morphologic changes of alcoholic and nonalcoholic fatty liver disease are indistinguishable,
they are described together:
Three categories of liver alterations are observed in fatty liver disease.
They can be present in any combination:
A. Steatosis (fatty change)
B. Hepatitis (alcoholic or steatohepatitis)
C. Fibrosis.
All changes in alcoholic liver disease begin in acinus zone 3 and extend outward toward the
portal tracts with increasing severity of injury.
1. Hepatic Steatosis (Fatty Liver).
Fat accumulation typically begins in centrilobular hepatocytes zone 3.
As steatosis progresses fat accumulation spread from central vein to periportal regions.
Soft yellow greasy liver.
Fatty change is completely reversible if there is abstention from further intake of alcohol.
2. Alcoholic (Steato-) Hepatitis. Alcoholic hepatitis is characterized by:
A. Hepatocyte swelling and necrosis:
Foci of cells undergo swelling (ballooning) and necrosis.
Swelling results from the accumulation of fat and water.
B. Mallory-Denk bodies:
Eosinophilic material in ballooned hepatocytes.
tangled threads of intermediate filaments such as keratins 8 and 18 in complex with
other proteins such as ubiquitin.
, These inclusions are a characteristic but not specific feature of alcoholic liver disease
since they are also present in NAFLD, Wilson disease and in chronic biliary tract
diseases.
C. Neutrophilic reaction:
Accumulate around degenerating hepatocytes, particularly those having Mallory-Denk
bodies.
3. Alcoholic Steatofibrosis.
Activation of sinusoidal stellate cells and portal fibroblasts, giving rise to fibrosis.
Fibrosis first appears in centrilobular region as central vein sclerosis and spreading outwards
encircling individual or small clusters of hepatocytes in a chicken wire fence pattern.
These webs of scar eventually link to portal tracts and then begin to condense into central-
portal fibrous septa.
With developing nodularity, cirrhosis becomes established.
Established nodules by new webs of, perisinusoidal scarring leads to a classic micronodular
or Laennec cirrhosis first described for end-stage alcoholic liver disease.
RISK FACTORS
Gender. Women seem to be more susceptible to hepatic injury than men, although the majority
of patients are men. estrogen increases gut permeability to endotoxins.
Ethnic and genetic differences. In the United States, cirrhosis rates are higher for African
American drinkers than for white Americans drinker.
Genetic polymorphisms in detoxifying enzymes ALDH2.
Comorbid conditions. Iron overload and infections with HCV and HBV synergize with alcohol,
leading to increased severity of liver disease.
Exposure to alcohol causes steatosis, dysfunction of mitochondrial and cellular membranes,
hypoxia, and oxidative stress.
Hepatocellular steatosis results from
(1) shunting of normal substrates away from catabolism and toward lipid biosynthesis, as a
result of increased generation of reduced nicotinamide adenine dinucleotide (NADH) by the two
major enzymes of alcohol metabolism, alcohol dehydrogenase and acetaldehyde
dehydrogenase.
(2) impaired assembly and secretion of lipoproteins.
(3) increased peripheral catabolism of fat, thus releasing free fatty acids into the circulation.
