Alcoholic Liver Disease

Introduction

Alcohol is one of the most common causes of chronic liver disease worldwide. The risks of alcoholic liver disease (ALD) start from any level of regular drinking and increase with the amount being consumed.

In the UK, a unit of alcohol contains 8g of ethanol. Guidelines state that men and women should drink less than 14 units per week, which is approximately equivalent 6 pints of beer.

Patients with ALD may also have other risk factors for liver disease (e.g. non-alcoholic fatty liver disease, chronic viral infection), which may interact to increase disease severity.

Epidemiology

Liver disease is the 5^th biggest killer in the UK and ALD accounts for 5000 deaths per year in the UK. The male:female of ALD ratio is 2:1. Alcohol causes 4% of all diseases and costs the NHS £3 billion per year.

Risk factors

• Drinking pattern: although alcohol dependence increases the risk of ALD, many of those that develop ALD are not dependent on alcohol. Damage is more likely in binge drinkers as this gives the liver less time to recover
• Gender: women have a smaller volume of distribution, so have a higher alcohol concentration in the blood than males for the same amount of alcohol consumed
• Genetics: certain genes can predispose to ALD e.g. PNPLA3
• Obesity and nutrition: obesity increase the risk of liver-related mortality by 5-fold in heavy drinkers. In addition, excessive alcohol consumption is associated with nutritional deficiencies that increase morbidity.

Pathophysiology

Alcohol can produce a wide spectrum of disease, progressing from fatty change to hepatitis to cirrhosis.

Alcohol is metabolised in the liver via 2 pathways: alcohol dehydrogenase (80%) and microsomal ethanol-oxidising system (20%). These lead fatty acid accumulation as well the production of reactive oxygen species (ROS) and cytokines.

Fatty liver disease

Metabolism of alcohol produces fat in the liver. Large amounts of alcohol consumption leads to cells swelling with fat (steatosis). There is no liver cell damage yet and the changes are reversible once alcohol consumption stops.

In some cases, collagen is laid down around central hepatic veins (perivenular fibrosis) as stellate cells become myofibroblasts. This can then progress to cirrhosis without a preceding hepatitis.

Alcoholic hepatitis

In addition to fatty change, there is leucocyte infiltration and hepatocyte necrosis. Mallory bodies (cytoplasmic inclusions) and giant mitochondria can be seen. Mallory bodies are suggestive but not specific for alcoholic damage.

If alcohol consumption continues, hepatitis may progress to cirrhosis

Alcoholic cirrhosis

Represents advanced liver disease. Cirrhosis is usually micronodular.

Clinical features

As well as liver disease, alcohol disease can damage other organs:

• Gastrointestinal: oesophagitis, Mallory-Weiss tears
• Respiratory: pulmonary tuberculosis, pneumonia
• Cardiac: cardiomyopathy
• Neurological: neuropathy, cerebellar degeneration, dementia. Wernicke-Korsakoff syndrome may develop as a result of thiamine (vitamin B₁) deficiency
  • Wernicke syndrome: triad of confusion, encephalopathy and ophthalmoplegia. It is reversible but may progress to Korsakoff syndrome if thiamine deficiency continues.
  • Korsakoff syndrome: retrograde amnesia and confabulation. It is irreversible.
• Endocrine: pseudo-Cushing’s syndrome, hypoglycaemia, gout
• Reproductive: hypogonadism, foetal alcohol syndrome, infertility
• Psychiatric

Hepatic effects can be considered according to the pathological status, although there is considerable overlap in clinical features.

Alcoholic fatty liver disease

Patients are asymptomatic. The liver may be normal or slightly enlarged. This stage has a good prognosis and steatosis usually disappears after 3 months of abstinence from alcohol.

Alcoholic hepatitis

Presents with:

• Jaundice
• Hepatomegaly
• Malnutrition
• Chronic liver disease signs e.g. palmar erythema, ascites, peripheral oedema
• Complications of portal hypertension e.g. variceal bleeding
• Fever

Cirrhosis often coexists and develops if drinking continues. Prognosis is significantly worse than fatty liver disease. 30% of patients die in the acute phase, particularly if there is hepatic encephalopathy or raised INR. Patients with acute hepatitis often deteriorate in the first 1-3 weeks in hospital. Jaundice takes up to 6 months to resolve even if abstaining from alcohol.

Alcoholic cirrhosis

The final stage of liver disease from alcohol abuse. Signs of chronic liver disease are present, although patients can still feel well with few symptoms.

Cirrhosis usually present with complications, usually variceal bleeding, jaundice or ascites. Other signs of decompensation include encephalopathy and hepatocellular carcinoma.

Investigations

Aim to establish alcohol misuse and exclude alternative causes of liver disease. The severity of liver damage should also be assessed.

Establish alcohol misuse

Alcohol misuse can be established through a clinical history obtained from the patient and their friends and family.

Blood tests can support alcohol misuse, including:

• FBC: macrocytosis
• Gamma-glutamyltransferase (GGT): raised in alcohol misuse

Exclude alternative diagnoses

Blood tests include:

• Viral serology: check for hepatitis A-E, EBV, CMV
• Ferritin: raised in haemochromatosis
• LFT and GGT: check for raised bilirubin, ALT and ALP
• Autoantibodies: ANCA, ANA, AMA
• Immunoglobulin levels: IgM, IgG
• Caeruloplasmin: reduced in Wilsons’s disease
• Alpha₁-antitrypsin levels

Assess severity

Blood tests:

• Folate levels
• Clotting studies: prolonged INR and APTT in advanced cirrhosis
• U&E: check for hepatorenal syndrome
• FBC: check for anaemia (gastrointestinal bleeding)

Imaging studies:

• Ultrasound scan and elastography: check liver size, shape and degree of fibrosis
• CT abdomen: checks for hepatosplenomegaly and collateral vessels
• Endoscopy: visualise and treat varices
• Liver biopsy: assesses severity of cirrhosis and support diagnosis

Management

Advising patients to stop drinking is the most important intervention. Assistance is effective even after cirrhosis has developed. Chlordiazepoxide should be used to prevent withdrawal symptoms.

Patients should be screened for infections; spontaneous bacterial peritonitis can be diagnosed on ascitic tap and should be treated with antibiotics.

Nutrition

• IV thiamine (e.g. Pabrinex) is important in preventing Wernicke-Korsakoff encephalopathy
• IV vitamin K should be provided to prevent bleeding
• A diet high in protein and vitamin supplements is recommended
• Enteral feeding via large-bore nasogastric tube in severely ill patients

Corticosteroids

Effective in patients with severe alcoholic hepatitis and increases survival. Contraindications include sepsis and variceal bleeding.

Liver transplantation

A controversial treatment in ALD. Most centres require at least 6 months of assistance from alcohol before being considered for transplant. However, the outcomes of transplants in ALD are generally good.

Preventing relapses

Group therapy and self-help are useful in preventing relapses. Drugs that assist in preventing relapses include acamprosate, disulfiram and naltrexone.

Complications

• Portal hypertension and variceal haemorrhage
• Hepatic encephalopathy
• Ascites
• Hepatocellular carcinoma
• Alcohol-related conditions e.g. Wernicke-Korsakoff encephalopathy
• Alcohol withdrawal and delirium tremens

Prognosis

Fatty liver disease has a good prognosis. However, hepatitis and cirrhosis have much worse outcomes; 5-year survival is 50%.