Skip to content
Explore atlas
PH-GI32

Alcohol-related liver disease

How the liver breaks down alcohol, why excess NADH, acetaldehyde and oxidative stress fill hepatocytes with fat and injure them, and how fatty liver can progress to alcoholic hepatitis and micronodular cirrhosis.

  • Free preview
  • 4 steps · 9 questions
  • 3D disease scene

By the end, you can

  • Describe how the liver oxidises alcohol through alcohol dehydrogenase, aldehyde dehydrogenase and CYP2E1, and what each pathway produces.
  • Explain how excess NADH and reduced fat export cause alcohol-related fatty liver, and why it reverses when drinking stops.
  • Explain how acetaldehyde, oxidative stress and gut endotoxin drive alcoholic hepatitis, and relate them to ballooning, Mallory–Denk bodies, neutrophils and pericellular fibrosis.
  • Explain why alcohol-related scarring begins round the central veins and how it leads to micronodular cirrhosis.
  • Recognise the classic blood tests, appearances and severity scores, and explain how abstinence, glucocorticoids, nutrition and transplantation act on the mechanism.

What it is

Alcohol-related liver disease (alcohol-associated liver disease) is liver injury caused by heavy drinking over months to years. It is a spectrum whose stages often overlap in one liver: fatty liver (steatosis), present in most heavy drinkers and reversible; alcoholic hepatitis (steatohepatitis), with injured hepatocytes, neutrophils and scar round the central veins; and cirrhosis. The amount and duration of drinking set the risk, but only a minority of heavy drinkers develop hepatitis or cirrhosis.

3 types to tell apart
Alcohol-related fatty liver (steatosis)
Fat in the hepatocytes, worst round the central veins; found in more than nine in ten heavy drinkers, usually silent, and it clears within weeks of stopping.
Alcoholic hepatitis
Fat with ballooned hepatocytes, Mallory–Denk bodies, neutrophils and pericellular fibrosis; from a mild finding on a blood test to a severe illness with jaundice and liver failure.
Alcohol-related cirrhosis
Scar ringing small regenerative nodules (micronodular cirrhosis); its complications are those of any cirrhosis.

Normal function

The liver oxidises alcohol in two steps

Alcohol (ethanol) is absorbed mostly from the small intestine and reaches the liver first in portal blood. A little is broken down by alcohol dehydrogenase in the stomach lining on the way, but the body cannot store alcohol, so the oxidise most of it as a priority, ahead of their usual fuels.

Two enzymes do most of the work. Alcohol dehydrogenase (ADH), in the cytoplasm, oxidises ethanol to acetaldehyde, a reactive and toxic molecule; aldehyde dehydrogenase (ALDH2), in the mitochondria, oxidises acetaldehyde to acetate, which leaves the liver and is burned to carbon dioxide and water in muscle and heart. Each step hands electrons to the coenzyme NAD⁺, turning it into NADH.

A third route, the microsomal ethanol-oxidising system in the smooth endoplasmic reticulum, uses the cytochrome P450 enzyme CYP2E1. It handles little alcohol in occasional drinkers, but regular heavy drinking induces it, so it can carry about a fifth of the load, producing reactive oxygen species as it works. CYP2E1 is concentrated in , round the , where blood arrives last and oxygen is lowest; this is where alcohol injury begins.

Point to it on the model
How the liver oxidises alcoholSchematic
  1. EthanolAbsorbed mostly from the small intestine; cannot be stored
  2. NAD⁺ to NADH
    NormalAlcohol dehydrogenase (cytoplasm)Most alcohol, most of the time
    ChangeCYP2E1 (smooth ER)Induced by heavy drinking; makes reactive oxygen species
  3. ChangeAcetaldehydeReactive; binds proteins and DNA
  4. aldehyde dehydrogenase 2 (mitochondria); NAD⁺ to NADH
    NormalAcetateLeaves the liver; burned in muscle and heart

Simplified. A little alcohol is oxidised by alcohol dehydrogenase in the stomach lining before it reaches the liver; an inactive ALDH2 variant lets acetaldehyde build up.