Alcoholic liver disease (ALD) covers a spectrum of disease which includes 3 conditions:
- Alcoholic fatty liver disease - fatty build-up in the liver. Reversible with alcohol cessation.
- Alcoholic hepatitis - inflammation of the liver. If mild it is reversible with permanent abstinence.
- Cirrhosis - scar tissue formation. It is irreversible. Abstinence can prevent further damage.
It causes approximately 3 million deaths annually (5% of deaths)
14 units weekly is the upper limit for both men and women. It should also be spread over 3+ days (not more than 5 units daily).
Pregnant women should abstain completely, otherwise they run the risk of causing foetal alcohol syndrome.
Pathophysiology
Chronic, heavy alcohol ingestion will not always result in ALD. Approximately 10-20% of alcohol abusers develop alcoholic hepatitis/cirrhosis.
Alcohol is metabolised in the liver through 2 pathways:
- Alcohol dehydrogenase - alcohol dehydrogenase is a hepatic enzyme which converts alcohol → acetaldehyde. Acetaldehyde is then converted to acetate by acetaldehyde dehydrogenase. Through this process, NAD is also reduced to NADH as a byproduct. When there is excessive NADH, we inhibit gluconeogenesis and also increase fatty acid oxidation. This promotes fatty infiltration of the liver.
- CYP2E1 - generates free radicals through oxidation of NADPH → NADP.
Chronic alcohol use also causes hepatic macrophages to produce TNF-a and ROS which causes oxidative stress and mitochondrial dysfunction
Normally we have antioxidants such as glutathione and vitamin E but with alcohol-use disorder we get deficiencies in these molecules. As a result, oxidative stress then causes hepatocyte necrosis and apoptosis.
⚠️ Risk factors
- Prolonged heavy alcohol consumption
- Hepatitis C
- Female sex - develops more rapidly in women than in men. However most ALD patients are still male.
🧰 Presentation
- Abdominal pain - RUQ pain and discomfort.
- Jaundice - more common in severe alcoholic hepatitis.
- Hepatomegaly - suggestive of fatty liver or alcoholic hepatitis.
- Ascites - common complication of cirrhosis.
- Weight loss/weight gain - weight loss and anorexia are common but weight gain may be due to ascites/oedema with portal hypertension.
- Fatigue
- Portal hypertension - due to cirrhosis of the liver
- Pruritus - due to accumulation of bile salts in the skin layers with jaundice.
- Haematemesis and melaena - due to oesophageal or gastric varices, gastric irritation and coagulopathy.
- Spider naevi (spider telangiectasia) - central red spot with deep red extensions that radiate outwards like spiders.
- Splenomegaly - as a result of portal hypertension. Hepatomegaly may also be present early on, but with advanced cirrhosis, the liver shrinks.
- Palmar erythema
- Gynaecomastia - due to altered sex hormone metabolism.
- Caput medusae - engorged para-umbilical veins once again due to portal hypertension.
- Dupuytren’s contracture - a thickened palmar fascia associated with severe liver disease.
- Asterixis - flapping motions of outstretched hands that are dorsiflexed. It represents a hepatic encephalopathic state that occurs in severe ALD.
🔍 Investigations
- FBC
- Anaemia is a common finding, but can be due to multiple things such as iron deficiency, GI bleeding, folate/B12 deficiency, hypersplenism, haemolysis.
- Leukocytosis
- Thrombocytopenia due to alcohol-induced bone marrow suppression.
- High MCV
- LFTs
- ⭐️ ALT/AST both raised with AST 2x more than ALT.
- ALP may be raised, representing cholestasis.
- Low albumin representing poor synthetic function.
- ⭐️ GGT raised. It has a better sensitivity of ~70% for liver injury and alcohol use.
- Clotting - an prolonged PT or raised INR indicates advanced cirrhosis or liver failure. It is also a useful prognostic indicator.
- U&Es - may be deranged in hepatorenal syndrome.
- Hyponatraemia frequent in advanced cirrhosis.
- Hypokalaemia and hypophosphataemia commonly cause muscle weakness in ALD.
- Hypomagnesaemia can predispose patients to seizures during withdrawal.
- 🥇 Ultrasound - may show fatty changes early on (seen as more echogenic substance in the liver).
- Another type of US that can be done is a FibroScan which measures elasticity of the liver with high frequency sound waves. It assists in assessing degree of cirrhosis present.
- Endoscopy - to assess and treat oesophageal varices.
- CT/MRI to look for fatty changes once again, signs of HCC, hepatosplenomegaly and abnormal vascular changes as well as ascites.
- 🏆 Liver biopsy - to confirm alcoholic hepatitis or cirrhosis. NICE recommend a biopsy when steroid treatment is being considered.
🧰 Management
Alcohol abstinence coupled with alcohol withdrawal management needs to be implemented as first-line management. Detoxification is needed along with nutritional support (especially thiamine).
🥇 For mild alcohol dependence, GP advice and brief interventions within the primary care setting or during inpatient hospitalisations. Ideally the patient and physician develop a plan for decreasing alcohol consumption.
🥇 For moderate-severe alcohol dependence, psychosocial interventions such as CBT/counselling is indicated. Pharmacotherapy is also indicated first-line.
The first-line medications used are (not all 3 at once, just 1 of the 3):
- Naltrexone - 50-100mg OD for 3-4 months. It can also be given once monthly for 6 months as a 380mg IM injection. Can precipitate opioid withdrawal if the patient has been using opioids as well. It works by reducing pleasurable effects of alcohol.
- Acomprosate - 666mg orally 3x daily for 3-4 months. It works by reducing cravings for alcohol.
- Disulfiram - 500mg OD for 1 week then 250mg OD. It works by sensitising the individual to alcohol (i.e. inducing nausea and vomiting).
Alcohol rehabilitation and behaviour modifications need to be implemented but we need to treat the withdrawal syndrome that accompanies abstinence.
To treat withdrawal we use:
🥇 Diazepam or oxazepam or chlordiazepoxide these are all BDZs that combat withdrawal effects.
🥈 Lorazepam
This is to diminish the delirium tremens and seizures.
🥇 IV pabrinex/Thiamine is also given to prevent Wernicke’s encephalopathy. Pabrinex is a combination of B vitamins. Thiamine can be given orally following pabrinex administration.
All of this is coupled with supportive care such as hydration and reassurance.
Steroids have been shown to improve outcomes over 1 month with severe alcoholic hepatitis but infection and GI bleeds should be treated prior to any steroid use. We can use Maddrey’s discriminant function to determine who would benefit from steroid administration. It is calculated using the PT and bilirubin concentration.
- 🥇 Prednisolone - 40mg orally OD.
Pentoxyfilline is an oral anti-TNF agent that can sometimes be used but the STOPAH study showed that prednisolone improved survival at 1 month but pentoxyfylline did not.
If a patient has abstained for 3 months they then may be eligible for referral for liver transplant if the disease is so severe and warrants the referral.
Complications
- WIthdrawal - presents with a multitude of issues. Symptoms start at 6-12 hours, these include:
- Sweating
- Tachycardia
- Anxiety
- Hallucinations
At 36 hours seizures have peak incidence.
At 48-72 hours, delirium tremens is at its peak incidence. ➡️
- Delirium tremens - is an acute onset of delirium due to alcohol withdrawal. Features include:
- Coarse tremor
- Confusion
- Delusions
- Auditory and visual hallucinations
- Fever
- Tachycardia
- Ataxia
- Arrhythmias
It has a mortality of 35% if not treated.
It occurs because chronic alcohol use results in GABA downregulation and glutamate up regulation to balance the effects of alcohol (which is GABA stimulation). Removal of alcohol causes a hyper-excited state then coupled with excessive adrenergic activity.
An acute neurological condition occurring due to thiamine deficiency. It presents with a clinical triad of:
- Ophthalmoparesis with nystagmus
- Ataxia
- Confusion
If this is not treated with urgent thiamine replacement, one could develop Korsakoff syndrome which can then be termed Wernicke-Korsakoff syndrome.
With WKS we add the amnesia (both anterograde and retrograde amnesia) to the aforementioned symptoms.
Wernicke’s encephalopathy has a high mortality rate if untreated and WKS is often irreversible, requiring full-time institutional care.