Alcoholic liver disease

Dr. Vaishali DAssistant Professor

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Objectives

• What is ALD?• 3 phases-steatosis,AlcoholicHepatitis&

fibrosis• Pathogenesis• Morphology• Clinical features• Lab Diagnosis

• Excessive alcohol consumption is the leading cause of liver disease.

• Alcoholic liver disease comprises of three main stages

1. Hepatic steatosis2. Alcoholic hepatitis3. Cirrhosis

Hepatic steatosisPathogenesis :• Fatty change is an acute, reversible manifestation of

ethanol ingestion.• Ethanol causes

– Increased fatty acid synthesis by causing catabolism of fat in the peripheral tissues

– Acetaldehyde which is metabolite of ethanol converts NAD+ to NADH. An excess NADH stimulates lipid biosynthesis.

– Also decreases oxidation of fatty acid by mitochondria due to reduced availability of NAD-req. for oxidation of fatty acid

– Acetaldehyde impairs the function of microtubules, resulting in decreased transport of lipoproteins from liver

• Collectively these metabolic consequences produce fatty liver.

Metabolism of ethanol. ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase

• Pathology:• Gross:

– The liver becomes yellow, greasy and is enlarged (up to 4 to 6 kg)

– The increase in weight is because of accumulation of fat

• Microscopy:• Following even moderate intake of alcohol,

small (microvesicular) lipid droplets accumulates in the liver

• With chronic intake of alcohol, more lipid accumulates, creating a large macrovesicular globules, compressing the nucleus the periphery.

Fatty change –liver(Steatosis)

Alcoholic Fatty Liver

• Clinical presentation of alcoholic steatosis– Hepatomegaly – Mild elevation of serum bilirubin, alkaline

phasphatase and gamma GT

Alcoholic hepatitis

• characterized by1. Hepatocyte swelling and necrosis2. Mallory bodies3. Neutrophilic inflammatory response4. Perivenular fibrosis

• Hepatocyte swelling and necrosis:– Single or scattered foci of cells undergo

swelling (ballooning degeneration) and necrosis

• Mallory bodies:– Scattered hepatocytes accumulate cytokeratin

intermediate filaments and other proteins– Visible as eosinophilic cytoplasmic inclusions

in degenerating hepatocytes

• Neutrophilic reaction:– Neutrophils accumulate around the

degenerating hepatocytes, particularly those having Mallory bodies.

– Lymphocytes and macrophages also enter portal tracts and spill into parenchyma

• Fibrosis :– Commonly seen in the form of sinusoidal and

perivenular fibrosis– Occasionaly periportal fibrosis may

predominate– Fibrosis mainly occurs because of the

activation of sinusoidal stellate cells and portal tract fibroblasts

• Clinical features:– Malaise, anorexia, weight loss, upper

abdominal discomfort, tender hepatomegaly.– Laboratory findings:

• Hyperbilirubinemia• Elevated ALP,GGT, moderate elevation of AST • Neutrophilic leucocytosis

• Alcoholic cirrhosis:– The final and irreversible form of alcoholic

liver disease– Usually evolves slowly– Gross:

• Initially the liver is yellow-tan, fatty and enlarged.• Later it is transformed into brown, shrunken,

nonfatty organ with multiple nodules.• Sometimes nodularity becomes very prominent

with scattred lager nodules creating a “hobnail” appearance on the surface of liver

Normal Liver

Cirrhosis

Alcoholic liver cirrhosis:

• Microscopy:– Initially fibrous septae are very delicate and

extend through sinusoids from central to portal regions as well as from portal tract to portal tract.

– As the fibrous septae dissect and surround nodules, the liver becomes more fibrotic, loses fat, and shrinks in size. (Laennec cirrhosis)

– Bile stasis may be seen.

Normal Liver Histology

Cirrhosis

Fibrosis

Regenerating Nodule

• Clinical features:– Features are similar to other forms of cirrhosis.– Malaise, weakness, weight loss, loss of appetite– Jaundice, ascites, and peripheral edema– Features of portal hypertension

Laboratory findings• Hematology-• HMG:Hb:Decreased• Anemia-Macrocytic• Clinical pathology-• Urine:Bile salt/pigment present• Ascitic /Peritoneal fluid-?• Biochemical-(LFTs)

– Hyperbilirubinemia – elevated serum aminotransferase (SGPT/SGOT)– Alkaline phasphatase, – Hypoproteinemia– Prothrombine time:Prolonged

• Case – 55yr/M chronic alcoholic,undernourished presented with nausea,anorexia.O/E : Pallor,icterus.P/A-distended,shifting dullness,mild tenderness.

• Features of Portal hypertension

Summary

• What is ALD?• Three phases with pathogenesis-• 1.Accumulation-steatosis-reversible• 2.Inflammation-Hepatitis• 3.Fibrosis-cirrhosis-irreversible• Morphology-• Fatty liver-Pale enlarge-initially• Later-cirrhosis-shrunkun• LFTs-deranged

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