Alcohol-Related Liver Disease

Alcohol use damages various organs and can lead to alcohol dependence syndrome. This section covers alcohol-related liver disease, alcohol dependence, alcohol withdrawal and Wernicke-Korsakoff syndrome.

Alcohol-related liver disease results from long-term excessive consumption of alcohol. The onset and progression of alcohol-related liver disease varies between people, suggesting there may be a genetic predisposition to having harmful effects of alcohol on the liver. The risk is increased with obesity and viral hepatitis.

 

Stages

There is a stepwise progression of alcohol-related liver disease.

 

1. Alcoholic fatty liver (also called hepatic steatosis)

Drinking leads to a build-up of fat in the liver. This process is reversible with abstinence.

 

2. Alcoholic hepatitis

Drinking alcohol over a long period causes inflammation in the liver cells. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.

 

3. Cirrhosis

Cirrhosis is where the functional liver tissue is replaced with scar tissue. It is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.

 

Recommended Alcohol Consumption

The UK recommendations (Department of Health updated 2021) are not regularly to drink more than 14 units per week. This should be spread evenly over 3 or more days and not more than 5 units in a single day. Binge drinking is defined as 6 or more units for women and 8 or more for men in a single session.

Pregnant women should avoid alcohol completely. Alcohol in early pregnancy can lead to:

  • Miscarriage
  • Small for dates
  • Preterm delivery
  • Fetal alcohol syndrome

 

Complications of Alcohol

  • Alcohol-related liver disease
  • Cirrhosis and its complications (e.g., hepatocellular carcinoma)
  • Alcohol dependence and withdrawal
  • Wernicke-Korsakoff syndrome (WKS)
  • Pancreatitis
  • Alcoholic cardiomyopathy
  • Alcoholic myopathy, with proximal muscle wasting and weakness
  • Increased risk of cardiovascular disease (e.g., stroke or myocardial infarction)
  • Increased risk of cancer, particularly breast, mouth and throat cancer

 

Examination Findings with Excess Alcohol

Signs suggestive of excessive alcohol consumption include:

  • Smelling of alcohol
  • Slurred speech
  • Bloodshot eyes
  • Dilated capillaries on the face (telangiectasia)
  • Tremor

 

Investigations

Blood test results suggesting alcohol-related liver disease include:

  • Raised mean cell volume (MCV)
  • Raised alanine transaminase (ALT) and aspartate transferase (AST)
  • AST:ALT ratio above 1.5 particularly suggests alcohol-related liver disease
  • Raised gamma-glutamyl transferase (gamma-GT) (particularly notable with alcohol-related liver disease)
  • Raised alkaline phosphatase (ALP) later in the disease
  • Raised bilirubin in cirrhosis
  • Low albumin due to reduced synthetic function of the liver
  • Increased prothrombin time due to reduced synthetic function of the liver (reduced production of clotting factors)
  • Deranged U&Es in hepatorenal syndrome

 

Liver ultrasound may show early fatty changes with “increased echogenicity”. Later, it can show changes related to cirrhosis. Ultrasound is used to screen for hepatocellular carcinoma in patients with cirrhosis.

Transient elastography (“FibroScan”) can be used to assess the elasticity of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring).

Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected.

CT and MRI scans can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.

Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis, particularly in patients where steroid treatment is being considered for alcohol-related hepatitis.

 

Management

The general principles of managing alcohol-related liver disease are:

  • Stop drinking alcohol permanently (drug and alcohol services are available for support)
  • Psychological interventions (e.g., motivational interviewing or cognitive behavioural therapy)
  • Consider a detoxication regime
  • Nutritional support with vitamins (particularly thiamine – vitamin B1) and a high-protein diet
  • Corticosteroids may be considered to reduce inflammation in severe alcoholic hepatitis to improve short-term outcomes (but not long-term outcomes)
  • Treat complications of cirrhosis (e.g., portal hypertension, varices, ascites and hepatocellular carcinoma)
  • Liver transplant in severe disease (generally 6 months of abstinence is required)

 

Alcohol Dependence

Alcohol dependence involves daily alcohol consumption, strong urges and cravings for alcohol, difficulty controlling consumption, tolerance to the effects of alcohol and withdrawal symptoms when stopping.

 

CAGE Questions

The CAGE questions can be used to quickly screen for harmful alcohol use:

  • C – CUT DOWN? Do you ever think you should cut down?
  • A – ANNOYED? Do you get annoyed at others commenting on your drinking?
  • G – GUILTY? Do you ever feel guilty about drinking?
  • E – EYE OPENER? Do you ever drink in the morning to help your hangover or nerves?

 

AUDIT Questionnaire

The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organisation to screen people for harmful alcohol use. It involves 10 questions with multiple-choice answers and gives a score. A score of 8 or more indicates harmful use.

 

Alcohol Withdrawal

Alcohol dependence involves a risk of withdrawal symptoms. These range from mild and uncomfortable to delirium tremens. Symptoms occur at different times after alcohol consumption ceases:

  • 6-12 hours: tremor, sweating, headache, craving and anxiety
  • 12-24 hours: hallucinations
  • 24-48 hours: seizures
  • 24-72 hours: delirium tremens

 

Delirium Tremens

Delirium tremens is a medical emergency associated with alcohol withdrawal. There is a 35% mortality rate if left untreated.

Alcohol is a depressant substance. It stimulates GABA receptors in the brain. GABA receptors have a relaxing effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors), causing a further relaxing effect on the electrical activity of the brain (glutamate is an “excitatory” neurotransmitter).

Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol. When alcohol is removed, the GABA system under-functions and the glutamate system over-functions, causing extreme excitability of the brain and excessive adrenergic (adrenalin-related) activity. This presents with:

  • Acute confusion
  • Severe agitation
  • Delusions and hallucinations
  • Tremor
  • Tachycardia
  • Hypertension
  • Hyperthermia
  • Ataxia (difficulties with coordinated movements)
  • Arrhythmias

 

Managing Alcohol Withdrawal

The CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.

Chlordiazepoxide (Librium) is a benzodiazepine used to combat the effects of alcohol withdrawal. Diazepam is a less commonly used alternative. It is given orally as a reducing regime titrated to the required dose based on the local alcohol withdrawal protocol (e.g., 10 – 40 mg every 1 – 4 hours). The dose is reduced over 5-7 days.

High-dose B vitamins (Pabrinex) is given intramuscularly or intravenously, followed by long-term oral thiamine. This is used to prevent Wernicke-Korsakoff syndrome.

 

Wernicke-Korsakoff Syndrome

Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol. Alcoholics often have poor diets and get many of their calories from alcohol. Thiamine deficiency leads to Wernicke’s encephalopathy and Korsakoff syndrome.

Features of Wernicke’s encephalopathy include:

  • Confusion
  • Oculomotor disturbances (disturbances of eye movements)
  • Ataxia (difficulties with coordinated movements)

 

Features of Korsakoff syndrome include:

  • Memory impairment (retrograde and anterograde)
  • Behavioural changes

 

Wernicke’s encephalopathy is a medical emergency with a high mortality rate. Korsakoff syndrome is often irreversible and results in patients requiring full-time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.

 

Last updated May 2023