Alcoholic Liver Disease

Alcoholic liver disease (ALD) is a clinical spectrum starting at alcoholic steatosis, and potentially ultimately resulting in liver cirrhosis.

Pathophysiology

1. Alcoholic beverages contain ethanol, which is metabolised by the liver
2. Ethanol is first converted into acetaldehyde by alcohol dehydrogenase (ADH).
3. Acetaldehyde is then converted into acetate by acetaldehyde dehydrogenase (ALDH).
4. The entire process of alcohol metabolization generates lots of NADH. This results in imbalance in the intracellular NAD+/NADH ratio which causes metabolic shifts towards increased formation of fatty acids and triglycerides, the latter of which ultimately accumulate in the liver leading to fatty liver, or steatosis.
5. This fatty accumulation can eventually progress into alcoholic hepatitis i.e. inflammation of the liver due to the excess alcohol intake.
6. A proportion of ethanol is also metabolised by the cytochrome CYP2E1 enzyme, which oxidises ethanol into acetate.
7. With chronic alcohol consumption, CYP2E1 levels rise. This is the reason people develop a tolerance to alcohol – more alcohol is needed to achieve the same level of intoxication that previously lower amounts of alcohol would have achieved.
8. The process of ethanol -> acetate by CYP2E1 releases reactive oxygen species which can damage parts of the cell such as mitochondria.
    

TL;DR – the metabolites produced from alcohol breakdown in the liver can have a toxic effect on the liver, mainly resulting in fat accumulation and direct hepatocyte damage. Over time, all the fat accumulation can result in hepatitis and even more over time, cirrhosis.

Progression

1. Alcoholic steatosis/fatty liver: Fat build-up in the liver from alcohol consumption
2. Alcoholic hepatitis: Inflammation of the liver due to alcohol consumption
3. Cirrhosis: Irreversible fibrosis of the liver

Clinical Features

The presentation of alcoholic liver disease can vary considerably between patients. Steatosis alone is often asymptomatic, although there may be hepatomegaly.

Alcoholic hepatitis may present with:

• Jaundice
• Hepatomegaly
• RUQ pain/discomfort
• Fever

If there is more advanced stage fibrosis or cirrhosis, patients may present with stigmata of chronic liver disease such as ascites, hepatosplenomegaly, peripheral oedema, spider naevi etc.

Investigations

Alcohol Dependency

Patients do not necessarily need to be alcohol dependent in order to develop alcoholic liver disease. However, the simple CAGE questionnaire can be used to screen for alcohol dependency. This involves asking the patient if they:

• CUT: Felt like they need to cut down on drinking
• ANNOYED: when people say they need to cut back
• GUILT: Feel guilty about drinking
• EYE-OPENER: Needed to drink as an ‘eye-opener’ first thing in the morning or to get rid of a hangover

Bloods

• FBC: May show a macrocytic anaemia due to chronic alcoholism
• LFT:
  • Elevated AST, gGT ALT. ALP may also be elevated in later stages of the disease
  • Bilirubin: May be elevated
  • AST:ALT Ratio: In alcoholic liver disease, AST is usually raised more than ALT. >1.5 rise suggests alcoholic liver disease
  • Albumin: Low due to reduced synthetic liver function
• Clotting screen: Elevated INR/PT due to deranged clotting function of the liver
• Hepatitis Serology: Ensure hepatitis is not the cause of symptoms
• Folate: May be low
• U&Es: Deranged in case of hepatorenal syndrome

Imaging

• Ultrasound: Looking for fatty changes
• FibroScan: If concerned about cirrhosis. Looks at the elasticity of the liver to look at the degree of cirrhosis.
• CT/MRI: If concerned about hepatocellular carcinoma

Biopsy

Liver biopsy is an invasive but excellent method of diagnosis as features of alcoholic liver disease can be identified on biopsy. Histological features include:

• Mallory Denk Bodies
• Neutrophil infiltration
• Hepatocyte ballooning
• Fibrosis in a ‘chicken-wire fence pattern’

Management

Conservative

• Advising patients to stop drinking – ideally life-long abstinence
• Nutritional support e.g. Pabrinex and thiamine/ensure adequate protein intake
• Motivational intervieweing/CBT

Steroids

• Corticosteroid treatment: This is sometimes used in the treatment of alcoholic hepatitis. NICE guidelines state they can be used for treating alcoholic hepatitis under very specific circumstances.
  • A score called Maddrey’s Discriminant Function for Alcoholic Hepatitis needs to be calculated. This score takes into account the PT and bilirubin mainly.
  • This tells us how much patients would benefit from steroid treatment. If the patient has a score of 32 or more and meets the following criteria, they can be offered corticosteroid treatment:
    • Has been treated for active infection/GI bleeding that is present
    • Renal impairment, if present, has been controlled
    • Risks vs benefits of steroid treatment have been explained

Transplant

In the UK, patients can be referred for consideration of liver transplant. NICE suggest patients should have decompensated liver disease which persists despite best medical management and 3 months of abstinence of alcohol.

Complications

Complications should be managed appropriately. There are many, both for chronic liver disease as well as specifically for alcohol related liver disease.

References

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513682/

https://www.ncbi.nlm.nih.gov/books/NBK546632/

https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/cld.172

https://www.mdcalc.com/maddreys-discriminant-function-alcoholic-hepatitis

https://www.nice.org.uk/guidance/cg100/chapter/Recommendations#ftn.footnote_10

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513682/