Definition

 • Liver disease due to excessive alcohol consumption.

• three patterns of disease are recognized: steatosis, alcoholic steatohepatitis (ASH), and cirrhosis.

Epidemiology

• extremely common.

 Pathogenesis

 • Alcohol metabolism in the liver generates high levels of nicotinamide adenine dinucleotide dehydrogenase (NADH) which stimulates fatty acid synthesis and production of triglycerides, leading to steatosis.

• In some individuals, oxidative stress from metabolism of alcohol leads to hepatocyte injury and necro- inflammatory activity (ASH).

 • Ongoing necro- inflammatory activity causes liver fibrosis which may progress to cirrhosis.

Presentation

• Steatosis and mild ASH are usually asymptomatic but are a common cause of mildly abnormal LFTs.

 • Severe alcoholic hepatitis following binge drinking causes malaise and fever, with marked elevation of LFTs. Jaundice may occur if there is marked loss of liver function.

• Alcoholic cirrhosis presents with complications of cirrhosis (e.g. ascites or ruptured oesophageal varices).

 Macroscopy

 • Steatosis causes an enlarged soft greasy liver.

 • ASH may cause a firm texture due to fibrosis in the liver.

• Cirrhosis causes diffuse nodularity of the liver.

Histopathology

 • All the changes are most severe in zone 3 near the central vein.

 • Steatosis shows large droplets of fat in hepatocytes which displace the nucleus to one side (macrovesicular / large droplet steatosis).

 • ASH shows ballooned hepatocytes which may contain Mallory– Denk bodies (clumps of dense pink material derived from the cytoskeleton) and an inflammatory infiltrate rich in neutrophils.

 • Fibrosis in ASH is typically pericellular but eventually forms fibrous bridges. Cirrhosis shows diffuse replacement of the liver by nodules of regenerating hepatocytes surrounded by fibrous bands.

 • Fatty change, ballooning, and cirrhosis may- co- exist.

 Prognosis

• Simple steatosis is fully reversible if alcohol consumption ceases.

 • Alcoholic hepatitis may resolve with cessation of alcohol consumption or may progress to fibrosis and cirrhosis. It is more likely to be progressive in women.

• Alcoholic cirrhosis has a poor prognosis, with 5- year survival rates of only 50%.