Alcoholic
Liver Disease
Content
• Alcoholic Liver Disease
• Symptoms
• Pathogenesis
• Laboratory Diagnosis
Objectives
At the end of this session, student will be able to –
• Explain
the Pathogenesis of Alcoholic Liver Disease
• Describe
the Symptoms of Alcoholic Liver Disease
• Explain
various laboratory diagnosis test for Alcoholic liver Disease
Alcoholic Liver Disease
Alcoholic liver disease is the term used to describe
the spectrum of liver injury associated with acute and chronic alcoholism
Signs
and Symptoms
• Progresses
in the liver as inflammation (hepatitis) and leads to fatty liver and cirrhosis
Risk
factors
• Occurs
after many years of excessive drinking
• Acute
alcoholic hepatitis – Binge drinking
• Severe
drinking – Life threatening
• Genetic
factors – Women have increased susceptibility to develop advanced alcoholic
liver disease with much lesser alcohol intake
• Malnutrition
• Toxicity
of ethanol in liver
• Infection
– Hepatitis C infection
Distinctive
forms of Alcoholic Liver Disease
Hepatic
Steatosis (Fatty liver)
•
Moderate consumption – Deposition
of small lipid droplets in hepatocytes
•
Excessive consumption –
accumulation of lipids in macrovascular
droplets
•
Nucleus gets displaced, Enlarged
liver
Alcoholic
hepatitis
•
Necrosis of liver cells in
centrilobular region
•
Neutrophillic reaction
•
Fibrosis
Alcoholic
Cirrhosis
•
Irreversible – Final stage
•
Liver turns brown, shrunken and non-fatty
appearance
•
Resembles post necrotic cirrhosis
Pathogenesis of Alcoholic Liver Disease
Ethanol
Metabolism
ADH = Alcohol Dehydrogenase; ALDH or ACDH =
Hepatic Acetaldehyde Dehydrogenase; NAD = Nicotinamide Adenine
Dinucleotide; NADH = Reduced NAD
• Direct
hepatotoxicity by ethanol to microtubules, mitochondria, membrane hepatocytes
• Hepatotoxicity
by ethanol metabolites
– Production
of protein-aldehyde adducts
– Formation
of malo-di-aldehyde-acetaldehyde (MAA)
• Oxidative
Stress – oxidation of ethanol by
cytochrome 450 oxidase, generation of free radicals and oxidative damage
• Immunological
attacks on hepatocytes
• Fibrogenesis
– Damaged
hepatocytes,
– Malon-di-aldehyde-acetaldehyde
adducts,
– Activated
kupffer cells, and
– Direct
stimulation by acetaldehyde
Laboratory
Diagnosis For Alcoholic Liver Disease
• Elevated
transaminases: increase in SGOT (AST) is more than that of SGPT (ALT)
• Rise
in serum γ-glutamyl transpeptidase
(γ-GT)
• Elevation in Serum alkaline phosphatase
• Hyperbilirubinaemia
• Hypoproteinaemia
with reversal of albumin-globulin ratio
• Prolonged
prothrombin time and partial thromboplastin time
• Anemia
and Neutrophilic leucocytosis
Summary
• Alcohol
liver disease is damage to liver and its function due to alcohol abuse
• Progresses
in the liver as inflammation (hepatitis) and leads to fatty liver and cirrhosis
• Major
forms include hepatic steatosis, hepatitis, cirrhosis
• Alcohol
is a caloric food source which displaces nutrients
• Causes
the activation of Kupffer cells and release of proinflammatory mediators
