Week 6 - C - Alcoholic liver disease - Metabolism, spectrum (steatosis, steatohepatitis, cirrhosis), features, management

Question 1

To keep health risks from alcohol to a low level if you drink most weeks, what are the UK advised alcohol guidelines?

Answer 1

men and women are advised not to drink more than 14 units a week on a regular basis

spread your drinking over 3 or more days if you regularly drink as much as 14 units a week

if you want to cut down, try to have several drink-free days each week

Question 2

How are the units of alcohol in a drink calculated?

Answer 2

Multiply the volume of the drink in litres by the alcohol concentration of the drink

Ie 70cl vodka at 40%

= 0.7 x 40

=28 units

Question 3

Excess alcohol consumption can have both acute and chronic effects on different organs

What are the different acute affects it can have on?

CNS

Gastrointestinal system

Respiratory system

Answer 3

CNS

• Accidents
• Violence

Gastrointestinal

• Oeseophagitis, Gastitis/ulceration
• Acute pancreatitis
• Fatty liver and alcholic hepatitis

Respiratory

• Overdose
• Aspiration

Question 4

What is the progressive effects of excess alcohol consumption on the liver?

Answer 4

Initially will cause a fatty liver and then will lead to inflammation - alcoholic hepatitis

Eventually it will start to causes fibrosis of the liver which will end as cirrhosis (scarring of the liver due to bridging fibrosis and nodular regeneration of hepatocytes)

Question 5

Chronic alcohol consumption can affected many different systems

What effects does it have on the

• CNS
• GI tract
• Cardiovascular
• Haematological
• Musculoskeletal

Answer 5

CNS - neuropathies, cerebellar degeneration, dementia, wenicke-korsakoff syndrome

GI-

• gastric erosions and ulcers, increases risk of some cancers
• Acute/chronic pancreatitis
• Cirrhosis of liver

Cardiovascular- hypertension, MI, stroke

Haematology - anaemia, bone marrow suppression

Musculoskeletal - proximal myopathy, osteoporosis

Question 6

Where is alcohol mainly metabolised?

What is the toxic substance produced during the metabolism of alcohol?

Answer 6

Alcohol is metabolized in the body mainly by the liver. The brain, pancreas, and stomach also metabolize alcohol.

The main toxic substance produced from the breakdown of alcohol (ethanol) is acetaldyhe

Question 7

Alcohol is metabolized by several processes or pathways.

Which enzymes are involved in the most common patway?

Answer 7

ADH - alcohol dehydrogenase

ALDH - aldehyde dehydrogenase

First, ADH metabolizes alcohol to acetaldehyde, a highly toxic substance and known carcinogen

Then, in a second step, acetaldehyde is further metabolized down to another, less active byproduct called acetate, which then is broken down into water and carbon dioxide for easy elimination (2).

Question 8

Which other enzymes are also involved in the breakdown of alcohol? (remember the main pathway in the liver is via alcohol and aldehyde dehydrogenase)

Answer 8

The enzymes cytochrome P450 2E1 (CYP2E1) and catalase also break down alcohol to acetaldehyde. However, CYP2E1 only is active after a person has consumed large amounts of alcohol, and catalase metabolizes only a small fraction of alcohol in the body

Question 9

Alcoholic liver disease—As the chief organ responsible for the breakdown of alcohol, the liver is particularly vulnerable to alcohol metabolism’s effects.

Alcoholic pancreatitis—Alcohol metabolism also occurs in the pancreas, exposing this organ to high levels of toxic byproducts such as acetaldehyde

What is the alcohol related liver disease spectrum?

Which point does it become irreversible?

Answer 9

REVERSIBLE

• Alcoholic fatty liver - More than 90 percent of people who drink heavily develop fatty liver
• Alcoholic hepatitis

IRREVERSIBLE

• Alcohol related cirrhosis (due to continual fibrosis of the liver)

Question 10

What is the condition known as when there is the abnormal retention of fat in the cells or organ?

What is seen on histology in this condition?

Answer 10

Steatosis, also called fatty change, is abnormal retention of fat (lipids) within a cell or organ. Steatosis most often affects the liver – the primary organ of lipid metabolism – where the condition is commonly referred to as fatty liver disease.

Fat vacuoles appear clear in hepatocytes on histology

Question 11

Alcoholic hepatitis is a diseased, inflammatory condition of the liver caused by heavy alcohol consumption over an extended period of time. It’s also aggravated by binge drinking and ongoing alcohol use.

What is the characteristic clinical presentation of a patient with alcoholic hepatitis? (presentation + examination)

Which features would make you think of a severe hepatitis?

Answer 11

Patient may present with

• Hepatomegaly
• Fever
• Ascites
• Jaundice
• Bleeding

Severe hepatitis - jaundice, encephalopathy, coagulopathy

Question 12

When alcoholic hepatitis develops, it may be the first time people realise that they are actually causing damage to their liver

What are the features of chronic liver disease?

Answer 12

Features

Spider naevia, palmar erythema, leuconychia (from hypoalbuminaemia), jaundice, finger clubbing, dupuytren;s contracture, gynaecomastia

Question 13

What are the different features of portal hypertension that can occur due to chronic liver disease?

What is the smelly breath known as? (breath of the dead)

Answer 13

Caput medusae

(oeseophageal and rectal varices also but usually only seen on actual endoscope/colonoscopy examination)

Hypersplenism

Thrombocytopenia

Fetor hepaticus - smells like a combination of rotten eggs and garlic

Question 14

What do blood tests show in a patient with alcoholic hepatitis?

Answer 14

Blood tests would show

• Increased bilirubin
• Increased WCC
• Increased INR
• Increased AST
• Decreased platelets - due to toic effect or hypersplenism from portal hypertension

Monitor creatinine in case of hepatorenal syndrome

Question 15

What s the management of alcoholic hepatitis?

What can be given for withdrawal symptoms from no alcohol?

Answer 15

Management is alcohol abstinence - vital

The typical treatment of alcohol withdrawal is with benzodiazepines such as chlordiazepoxide (or diazepam) (in patients with liver disease, lorazepam may be safer)

IV thiamine is also given as prophylaxis against Wernicke’s-Korsakoff syndrome due to long term alcohol consumption greatly lowering this vitamin (vit B1)

Question 16

What is used as prognostic scoring in cases of alcoholic hepatitis?

Answer 16

Maddrey’s discrimination factor (DF) or

Glasgow alcoholic hepatitis score (GAHS)

They roughly reflect mortality score

Question 17

What is considered for treatment in severe alcoholic hepaitis?

Generaly given if features of encephalopathy or Maddrey’s discrimination factor>32 (correlates to 45% mortality at 28 days)

Answer 17

Give the patient oral prednisolone

Question 18

To summarise, what are the complications of acloholic liver disease?

Answer 18

Alcoholic fatty liver ->

Alcoholic hepatitis (alcoholic steatohepatitis) ->

Cirrhosis ->

Hepatocellular carcinoma

Also portal hypertension, encephalopathy, hepatorenal syndrome

Malnutrition