Key Facts

Alcohol use disorder encompasses a spectrum from hazardous drinking to severe dependence. The UK has one of the highest rates of alcohol consumption in Europe. Alcohol misuse costs the NHS approximately £3.5 billion/year and is associated with over 200 disease and injury conditions.

Epidemiology

• Approximately 600,000 dependent drinkers in England; only ~18% access treatment
• Prevalence of hazardous drinking (AUDIT ≥8): approximately 25% of the adult population
• Male:female ratio approximately 2:1 for dependence
• Peak age of alcohol-related hospital admissions: 55-64 years
• Alcohol-specific deaths rising: 9,641 in England and Wales (2021) - highest on record
• Socioeconomic deprivation strongly associated with alcohol harm (the alcohol harm paradox)

Aetiology

• Genetic factors: heritability ~50-60%; polymorphisms in ADH1B and ALDH2 genes influence risk
• Neurobiological: alcohol enhances GABA (inhibitory) and inhibits glutamate (excitatory) neurotransmission; chronic use leads to neuroadaptation
• Psychological: co-morbid anxiety, depression, PTSD, ADHD; adverse childhood experiences (ACEs)
• Social/environmental: peer influence, availability, pricing, cultural norms, socioeconomic deprivation
• Behavioural: positive and negative reinforcement models; classical and operant conditioning

Pathophysiology

• Chronic alcohol exposure → upregulation of NMDA glutamate receptors and downregulation of GABA-A receptors
• Abrupt cessation → unopposed excitatory neurotransmission → withdrawal syndrome
• Hepatic metabolism: alcohol → acetaldehyde (via alcohol dehydrogenase) → acetate (via aldehyde dehydrogenase)
• Chronic use induces CYP2E1 (microsomal ethanol oxidising system), generating reactive oxygen species
• Progressive hepatotoxicity: steatosis → steatohepatitis → fibrosis → cirrhosis

Hazardous and Harmful Drinking

• May be asymptomatic or present with social/occupational consequences
• Incidental findings: raised GGT, raised MCV, abnormal LFTs
• Recurrent injuries, accidents, or attendances to Emergency Department

Alcohol Dependence

• Compulsion: strong desire or sense of compulsion to drink
• Impaired control: difficulty controlling onset, termination, or levels of use
• Tolerance: need for increased amounts to achieve desired effect
• Withdrawal: physiological withdrawal state on cessation or reduction
• Neglect: progressive neglect of alternative activities and responsibilities
• Persistence: continued use despite clear evidence of harmful consequences

Physical Complications

• Hepatic: fatty liver, alcoholic hepatitis, cirrhosis, hepatocellular carcinoma
• Gastrointestinal: pancreatitis (acute and chronic), oesophageal varices, Mallory-Weiss tears, gastritis
• Neurological: peripheral neuropathy, Wernicke encephalopathy, Korsakoff syndrome, cerebellar degeneration
• Cardiovascular: dilated cardiomyopathy, atrial fibrillation, hypertension
• Haematological: macrocytosis, thrombocytopenia, folate deficiency
• Metabolic: hypomagnesaemia, hypophosphataemia, hypoglycaemia

Red Flags

• Delirium tremens (onset 48-72 hours post-cessation): confusion, visual hallucinations, autonomic instability - mortality 5-15% if untreated
• Wernicke encephalopathy: ophthalmoplegia, ataxia, confusion - requires immediate IV Pabrinex
• Acute alcoholic hepatitis: jaundice, coagulopathy, encephalopathy - Maddrey DF ≥32 indicates severe disease
• Variceal haemorrhage: massive upper GI bleed - mortality 15-20% per episode
• Alcohol-related brain damage: cognitive impairment, personality change, self-neglect

Bedside

• AUDIT questionnaire: 10-item screening tool; score ≥8 hazardous, ≥16 harmful, ≥20 possibly dependent
• AUDIT-C: abbreviated 3-item version for primary care screening
• SADQ: 20-item severity assessment for dependence (score 0-60)
• Breath alcohol level: may be useful in acute settings
• Clinical Institute Withdrawal Assessment (CIWA-Ar): monitors withdrawal severity

Bloods

• LFTs: raised GGT (most sensitive marker), raised AST (AST:ALT ratio >2 suggests alcoholic liver disease)
• FBC: macrocytosis (raised MCV), thrombocytopenia
• Clotting: prolonged INR/PT suggests significant liver disease
• U&Es: hyponatraemia, hypokalaemia, hypomagnesaemia
• Phosphate: hypophosphataemia (refeeding risk)
• Carbohydrate-deficient transferrin (CDT): biomarker of heavy drinking over 2-3 weeks
• Ethyl glucuronide (EtG): urine or hair testing for recent alcohol use
• Serum B12 and folate: commonly deficient

Imaging

• Liver ultrasound: assess for steatosis, fibrosis, cirrhosis, hepatocellular carcinoma
• FibroScan (transient elastography): non-invasive assessment of liver fibrosis; >8 kPa suggests significant fibrosis
• CT head: if concern about subdural haematoma, cerebellar degeneration, or Wernicke encephalopathy (MRI preferred for Wernicke)

Special Tests

• Liver biopsy: gold standard for staging liver disease (rarely needed with FibroScan)
• Upper GI endoscopy: if varices suspected or upper GI bleed
• EEG: if seizure aetiology uncertain
• Neuropsychological testing: if alcohol-related brain damage suspected

Non-pharmacological

• Brief intervention (NICE CG115): 5-15 minute structured advice for hazardous/harmful drinkers; NNT ~8 for reduction to low-risk drinking
• Extended brief intervention: up to 4 sessions of motivational interviewing-based counselling
• Cognitive behavioural therapy (CBT): addresses maladaptive thought patterns and drinking triggers
• Mutual aid: Alcoholics Anonymous (12-step), SMART Recovery (CBT-based)
• Social support: housing, employment, relationship counselling
• Nutritional support: high-calorie diet, thiamine supplementation

Pharmacological

• Assisted withdrawal (NICE CG115):
  • Chlordiazepoxide: first-line for community/inpatient detoxification; typical reducing regimen over 7-10 days (e.g. 30 mg QDS reducing by 20% daily for moderate dependence)
  • Diazepam: alternative benzodiazepine; symptom-triggered regimens used in some units
• Thiamine supplementation:
  • Oral thiamine 100 mg TDS for mild/moderate risk
  • IV Pabrinex (2 pairs TDS for 3-5 days) for high-risk patients or suspected Wernicke encephalopathy
• Relapse prevention (NICE CG115):
  • Acamprosate 666 mg TDS (333 mg TDS if <60 kg): modulates glutamate; start after detoxification; continue for 6 months - COMBINE trial showed efficacy combined with behavioural therapy
  • Naltrexone 25 mg OD for 3 days then 50 mg OD: opioid antagonist; reduces reward from drinking - can cause hepatotoxicity; check LFTs
  • Disulfiram 200 mg OD: aldehyde dehydrogenase inhibitor; causes acetaldehyde accumulation with alcohol - supervised consumption recommended
  • Nalmefene 18 mg PRN: licensed for reduction of alcohol consumption in adults with alcohol dependence without withdrawal symptoms (NICE TA325)

Surgical

• Liver transplantation: considered for end-stage alcoholic liver disease with minimum 6 months abstinence (although increasingly flexible) - 5-year survival ~70%
• TIPSS (transjugular intrahepatic portosystemic shunt): for recurrent variceal haemorrhage or refractory ascites

Referral Criteria

• Specialist alcohol services: moderate-severe dependence (SADQ ≥16), previous complicated withdrawal, co-morbid mental or physical health problems
• Inpatient detoxification: severe dependence (SADQ >30), history of withdrawal seizures or delirium tremens, significant co-morbidity, unstable social situation
• Hepatology: suspected cirrhosis, Maddrey DF ≥32, liver transplant assessment
• Psychiatry: co-morbid severe mental illness, suicidality, dual diagnosis

Mortality and Outcomes

• Alcohol-specific mortality in England: approximately 14.8 per 100,000 population (2021)
• Delirium tremens mortality: 5-15% untreated, <1% with appropriate treatment
• Alcoholic hepatitis (Maddrey DF ≥32): 28-day mortality 30-50% without treatment; Glasgow Alcoholic Hepatitis Score ≥9 predicts poor prognosis
• Alcoholic cirrhosis: 5-year survival ~50% if drinking continues, ~70% with abstinence
• Alcohol-related brain damage: affects up to 35% of heavy drinkers to some degree; often irreversible

Complications

• Liver cirrhosis and hepatocellular carcinoma: risk increases with cumulative lifetime consumption
• Oesophageal varices: present in ~50% of patients with cirrhosis; 15-20% mortality per bleed
• Pancreatitis: alcohol is the cause in ~30-40% of acute pancreatitis cases in the UK
• Wernicke-Korsakoff syndrome: Wernicke encephalopathy is under-diagnosed; ~80% of untreated cases progress to Korsakoff syndrome
• Foetal alcohol spectrum disorder: leading preventable cause of intellectual disability; no safe level of alcohol in pregnancy
• Cancer risk: increased risk of oral, pharyngeal, oesophageal, liver, breast, and colorectal cancers

AUDIT Scoring

SADQ Scoring

UK Units Calculation

Landmark Trials