Conditions · Metabolism (biochemistry)
Alcoholic liver disease (biochemistry) !
Alcohol damages the liver in stages: fatty liver, alcoholic hepatitis and cirrhosis; excess NADH and acetaldehyde are the cause.
Updated 2026-11-01
Structures involved
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In biochemistry
- Alcohol dehydrogenase (ADH)
- Aldehyde dehydrogenase 2 (ALDH2)
- Cytochrome P450 2E1 (CYP2E1, MEOS)
- Ethanol
- Acetaldehyde
- Acetaminophen metabolism and NAPQI
In physiology
Why it happens
- Alcohol: how it injures the liver, brain, heart and fetus
- Fatty change (steatosis)
- Liver regeneration
- Intracellular accumulations: cholesterol, proteins, hyaline, glycogen
- Fibrosis in organs: TGF-β and the myofibroblast
- Chemical (toxic) cell injury: direct and after metabolism
What it is
A spectrum of liver injury from prolonged heavy drinking, from reversible fatty liver to alcoholic hepatitis and cirrhosis.
Who gets it
WHO estimates that alcohol causes millions of deaths a year and that cirrhosis is one of its main consequences. In Colombia and Latin America heavy episodic drinking is common and alcoholic liver disease is an important cause of cirrhosis.
Causes
- Prolonged heavy alcohol consumption
- Risk depends on the cumulative amount and pattern, not the type of drink
Risk factors
- Female sex (more damage with less alcohol)
- Obesity and metabolic syndrome
- Hepatitis B or C
- Genetic variants such as PNPLA3
- Malnutrition
- Smoking
Pathophysiology
Alcohol dehydrogenase and ALDH2 make a lot of NADH; the high NADH/NAD⁺ ratio slows β-oxidation and the Krebs cycle and supplies glycerol-3-phosphate, so fatty acids are esterified into triglycerides: fatty liver (macrovesicular steatosis). Export in VLDL cannot keep up. Acetaldehyde forms protein adducts (damaging microtubules and protein secretion, so the hepatocyte swells) and acts as a neoantigen. Induced CYP2E1 generates free radicals and lipid peroxidation, with less glutathione. Gut endotoxin activates Kupffer cells (TNF-α): neutrophilic inflammation and Mallory–Denk bodies (alcoholic hepatitis). Activated stellate cells lay down collagen, first around the central vein: fibrosis and finally cirrhosis.
Classification
- Alcoholic fatty liver (reversible with abstinence)
- Alcoholic hepatitis (acute, can be severe)
- Alcoholic fibrosis and cirrhosis
Symptoms and signs
- None in fatty liver, or an enlarged liver and right upper quadrant discomfort
- Jaundice, fever and a tender liver (alcoholic hepatitis)
- Fatigue, weight and muscle loss
- Ascites, spider naevi and palmar erythema
- Confusion (hepatic encephalopathy)
Diagnosis
- Clinical
- Drinking history (questionnaires such as AUDIT), signs of chronic liver disease and exclusion of other causes.
- Tests
- Transaminases with AST/ALT above 2 and AST rarely above 300–400 (ALT needs pyridoxal phosphate, scarce in drinkers); high GGT; high MCV; bilirubin, albumin and INR for function; severity scores (Maddrey, MELD); viral hepatitis markers.
- Imaging
- Ultrasound shows a bright liver (steatosis), nodules, a large spleen or ascites; elastography measures stiffness (fibrosis); endoscopy looks for varices.
Treatment
- Lifestyle
- Complete abstinence from alcohol: what most changes the outcome at every stage.
- Medical
- Nutritional support and replacement of thiamine, folate and other vitamins.
- Medical
- Severe alcoholic hepatitis: corticosteroids in selected cases.
- Medical
- Treatment of dependence: psychotherapy and drugs such as naltrexone, acamprosate or disulfiram.
- Surgical
- Liver transplantation for decompensated cirrhosis, after a period of abstinence and assessment.
Complications
- Cirrhosis and portal hypertension
- Oesophageal varices and gastrointestinal bleeding
- Ascites and spontaneous bacterial peritonitis
- Hepatic encephalopathy
- Hepatocellular carcinoma
- Hepatorenal syndrome
Prognosis
Fatty liver reverses within weeks without alcohol; severe alcoholic hepatitis has high short-term mortality; in cirrhosis, abstinence greatly improves survival.
Prevention
- Public health alcohol policies (price, availability, advertising)
- Early detection of risky drinking
- Hepatitis B vaccination
Test yourself
Think of the answer, then tap the question to see it.
Why does alcohol cause fatty liver?
Excess NADH slows β-oxidation and supplies glycerol-3-phosphate: fatty acids pile up as triglycerides.
Why is the AST/ALT ratio usually above 2 in alcoholic hepatitis?
Drinkers lack pyridoxal phosphate, which ALT needs more, and alcohol damages mitochondria, which are rich in AST.
Which hepatocyte inclusions are typical of alcoholic hepatitis?
Mallory–Denk bodies: aggregated keratin filaments.
Which measure most changes the outcome at every stage?
Complete abstinence from alcohol.
Related conditions
- Acetaminophen toxicity
- Disulfiram–ethanol reaction
- Cirrhosis
- Portal hypertension
- Hepatocellular carcinoma
- Upper gastrointestinal bleeding
- Acute pancreatitis
- Chronic pancreatitis
- Wernicke encephalopathy (thiamine deficiency)
- Lactic acidosis
Educational information, not medical advice. For any symptom, see a health professional.
Sources: Alcoholic liver disease: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026); Alcohol (World Health Organization, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).
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