4. Drug & toxin-induced liver disease

Question 1

Classification of drug & toxin-induced liver disease

Answer 1

1. Drug-induced liver disease
2. Alcoholic liver disease
   - Hepatic steatosis (fatty liver)
   - Alcoholic hepatitis
   - Alcoholic cirrhosis

Question 2

Pathogenesis of drug-induced liver disease

Answer 2

1. Direct toxicity of drug to hepatocytes
2. Hepatic conversion of drug to an active toxin
3. Drug or metabolite acting as a hapten to convert a cellular protein into an immunogen

Question 3

Pathogenesis of hepatic steatosis

Answer 3

1. Generation of excess NADH by alcohol dehydrogenase & acetaldehyde dehydrogenase
2. Excess NADH shunts normal substrates away from catabolism & towards lipid biosynthesis
3. Also, assembly & secretion of lipoproteins are impaired, leading to intracellular lipid accumulation

Question 4

Morphology of hepatic steatosis

Answer 4

1. Microvesicular (short-term) or macrovesicular
   (chronic intake) lipid globules within hepatocytes
2. Liver appears large, soft & yellow
3. Fatty change is completely reversible with abstention from alcohol
4. Centrilobular fibrosis develops with continued alcohol intake

Question 5

Pathogenesis of alcoholic hepatitis

Answer 5

1. Acetaldehyde-induced lipid peroxidation
2. Acetaldehyde-protein adduct formation
3. Increased production of reactive oxygen species
4. Impaired methionine metabolism which decreases
   intracellular glutathione levels, hence reducing
   hepatic resistance towards oxidative injury

Question 6

Morphology of alcoholic hepatitis

Answer 6

1. Hepatocyte injury & necrosis
2. Mallory bodies
3. Neutrophilic reaction
4. Centrilobular fibrosis

Question 7

Pathogenesis of alcoholic cirrhosis

Answer 7

End stage of prolonged alcoholic hepatitis

Question 8

Morphology of alcoholic cirrhosis

Answer 8

1. Micronodular parenchymal nodules (<3mm)
2. Fatty change (minimally evident in late stages)
3. Mallory bodies