Alcoholic Liver

DiseaseLecture 24

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ETHANOLExcessive alcohol (ethanol) consumption is

the leading cause of liver disease

in most Western countries.

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Forms of alcoholic liver disease

(1)Hepatic steatosis (fatty liver disease)

(2) Alcoholic hepatitis (3) Cirrhosis.

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Fatty Liver /SteatosisDefinition:• Fatty liver is the collection of excessive

amounts of triglycerides and other fats inside liver cells.

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Description

• The liver is the organ responsible for changing fats eaten in the diet to types of fat that can be stored and used by the body. 

• Triglycerides are one of the forms of fat stored by the body and used for energy and new cell formation.

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The break down of fats in the liver can be disrupted by 

 

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Morphology of

1.Hepatic Steatosis (Fatty Liver). After even moderate intake of alcohol,

microvesicular lipid droplets accumulate in hepatocytes.

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1.Hepatic Steatosis (Fatty Liver). After even moderate intake of alcohol,

microvesicular lipid droplets accumulate in hepatocytes.

With chronic intake of alcohol, lipid accumulates creating

that compress and displace the hepatocyte nucleus to the periphery of the cell.

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The normal adult liver weighs 1400 -1600 gm

Macroscopically, the fatty liver of chronic

alcoholism is a large (as heavy as 4 to 6 kg), soft organ that is yellow and greasy.

The fatty change is completely reversible if there is abstention from further intake of alcohol.

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Morphology 2. Alcoholic Hepatitis (Alcoholic Steatohepatitis).

Alcoholic hepatitis is characterized by: 1. Hepatocyte swelling and necrosis2. Mallory bodies: Mallory bodies are visible as eosinophilic cytoplasmic clumps in hepatocytes.

3. Neutrophilic reaction 4. Fibrosis

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Mallory BodiesLarge, poorly defined accumulations of eosinophilic material in the cytoplasm of damaged hepatic cells in certain forms of cirrhosis especially those due to alcoholism.

• Synonym(s): alcoholic hyalin, alcoholic hyaline bodies

Mallory body, Mallory-Denk body, and Mallory's hyaline

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ETHANOL 14 Mallory body with the characteristic twisted-rope appearance (centre of image - within a ballooning hepatocyte). H&E stain

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Alcoholic cirrhosis. A, The characteristic diffuse nodularity of the surface reflects the processes of nodular regeneration and scarring. The greenish tint of some nodules is

due to bile stasis. A hepatocellular carcinoma is present as a budding mass at the lower edge of the right lobe (lower left).

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B, The microscopic view shows nodules of varying sizes entrapped in blue-staining fibrous tissue. The liver capsule is at the top (Masson trichrome).

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Alcoholic liver disease. The interrelationships among hepatic steatosis, hepatitis, and cirrhosis are shown, depicting key morphologic

features.

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Pathogenesis. • Short-term ingestion of as much as 80 gm of

alcohol over one to several days generally produces mild, reversible hepatic steatosis.

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• Daily intake of 80 gm or more of ethanol generates significant risk for severe hepatic injury, and daily ingestion of 160 gm or more for 10 to 20 years is associated more consistently with severe injury.

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• Only 10% to 15% of alcoholics, however, develop cirrhosis.

• Thus, other factors must also influence the development and severity of alcoholic liver disease.

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Factors other than alcohol1. Gender. Women 2. Ethnic differences 3. Genetic factors

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Hepatocellular steatosis results from(1) shunting of normal substrates away from

catabolism and toward lipid biosynthesis(2) impaired assembly and secretion of

lipoproteins; (3) increased peripheral catabolism of fat.

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Clinical Features • 1.Hepatic steatosis (fatty liver):

Hepatomegaly, • with mild elevation of serum bilirubin and

alkaline phosphatase levels.• Severe hepatic dysfunction is unusual.

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Treatment• Alcohol withdrawal and

• the provision of an adequate diet are sufficient treatment.

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2. Alcoholic hepatitis tends to appear acutely, usually following a

bout of heavy drinking.

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Clinical features of Alcoholic Hepatitis

1. Malaise,2. Anorexia,3. Weight loss, 4. Upper abdominal discomfort,

5. Tender hepatomegaly,

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Laboratory findings: hyperbilirubinemia, elevated alkaline phosphatase, neutrophilic leukocytosis.

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• An acute cholestatic syndrome may appear, resembling large bile duct obstruction.

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• The outlook is unpredictable; each bout of hepatitis incurs about a 10% to 20% risk of death.

• With repeated bouts, cirrhosis appears in about one third of patients within a few years.

• Alcoholic hepatitis also may be superimposed on established cirrhosis.

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• With proper nutrition and total cessation of alcohol consumption, the alcoholic hepatitis may clear slowly.

• However, in some patients, the hepatitis persists, despite abstinence, and progresses to cirrhosis.

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Laboratory findings:

• Elevated serum aminotransferase,• Hyperbilirubinemia,• Elevation of serum alkaline phosphatase,• Hypoproteinemia, • Anemia.

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SGOT, SGPT

Cholestasis

Diagnosis

• In some instances, liver biopsy may be indicated, since in about 10% to 20% of cases of presumed alcoholic cirrhosis, another disease process is found.

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Silent Cirrhosis• Finally, cirrhosis may be clinically silent,

discovered only at autopsy or• when stress such as infection or trauma tips

the balance toward hepatic insufficiency.

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Prognosis• Five-year survival approaches 90% in

abstainers who are free of jaundice, ascites, or hematemesis;

• it drops to 50% to 60% in those who continue to imbibe.

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In the end-stage alcoholic the proximate causes of death are

(1) hepatic coma, (2) massive gastrointestinal hemorrhage, (3) intercurrent infection (4) hepatorenal syndrome(5) hepatocellular carcinoma

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Summary• Alcoholic liver disease is a chronic disorder

featuring steatosis, hepatitis, progressive fibrosis, cirrhosis, and marked derangement of vascular perfusion.

• It can be regarded as a maladaptive state in which cells in the liver respond in an increasingly pathologic manner to a stimulus (alcohol) that originally was only marginally harmful.

• For some unknown reason, cirrhosis develops in only a small fraction of chronic alcoholics.

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Drug- and Toxin-Induced Liver Disease

The drugs and toxins which cause hepatic injury along with their specific effects.

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BKMC

1

2

3

19

21

4 5

67

8 5

9 10

1113

14 9

10 8

1516

17

181

1

19 20

1

21

22

22

23 24

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