Alcoholic Liver Disease

Question 1

Causes of liver disease

Answer 1

Alcohol consumption
Viral infections e.g. hepatitis
Inherited disease e.g. Wilson's
Vascular abnormalities
Toxins, cancer, biliary tract disorders, infections, etc.

Question 2

What is the recommended number of units per week in UK?

Answer 2

14 units

Question 3

What classifies as ‘binge drinking’

Answer 3

> 6 units in a single session

- major cause for A&E admissions

Question 4

What are the short term affects of alcohol on the body?

Answer 4

1) Loss of inhibition (impaired judgement)
2) Decreased respiratory rate
3) GI disturbances
4) Loss of consciousness
5) Impotence (inability to take effective action)
6) Acute poisoning
7) Complexion/effect on appearance
8) Unintentional injuries

Question 5

What are the long term effects of alcohol on the body?

Answer 5

1) Liver disease
2) Cancer
3) Pancreatitis
4) GI ulceration
5) Osteoporosis (malabsorption)
6) Infertility
7) Heart disease and stroke due to cholesterol
8) Increased blood pressure
9) Obesity
10) Dementia

Question 6

Stages of liver disease

Answer 6

Healthy liver
Fatty liver (steatosis)
Fibrosis
Cirrhosis

Question 7

How is alcohol metabolised?

Answer 7

Alcohol dehydrogenase to acetaldehyde
Acetaldehyde dehydrogenase to acetic acid
Further metabolised to fatty acids

Question 8

What happens to alcohol metabolism in chronic consumption?

Answer 8

Impaired efficiency of aldehyde dehydrogenase

1) Build up of acetaldehyde = inflammation, necrosis (inflammatory immune response- protein function)
2) Acetaldehyde = inhibits alcohol dehydrogenase (increased levels of circulating alcohol- causes effects to persist for longer)

Upregulation of CYP450 2E1

• Microsomal ethanol oxidising system responsible for ~10% in low consumption
• High consumption = increased free radicals produced causing further damage

Question 9

What is fatty liver?

Is it reversible? What does it effect?

Answer 9

Accumulation of fat in the hepatocytes
- due to disruption of metabolic pathways

Reversible and rarely symptomatic
- doesn’t effect metabolism of food/drugs

Question 10

What is the form of acute alcoholic hepatitis that is commonly caused by alcohol consumption? (AAH)

Answer 10

Steatohepatitis

Question 11

What is steatohepatitis?

Answer 11

Accumulation of fat + hepatocellular injury

• inflammation and fibrosis
• can cause liver pain, vomiting, confusion
• improves with abstinence (though many will still develop cirrhosis despite)

Question 12

What is thought to be the mechanisms of injury for steatohepatitis?

Answer 12

Poorly understood

• oxidative stress
• aldehyde accumulation
• altered protein function

Question 13

What is fibrosis/cirrhosis?

Answer 13

Inflammation + fibrogenesis + collagen deposition

• the more episodes of inflammation, the more likely it is to develop
• irreversible, unlike acute episodes
• direct injury from free radicals and expression of inflammatory cytokines
• may exhibit signs of decompensation
• abstinence is key in management

Question 14

Will cirrhosis occur in all patients with multiple episodes of inflammation?

Answer 14

No, dependent on individuals

Increased susceptibility depends on:

• genetics
• age
• gender
• BMI
• race
• consumption patterns

Question 15

Give the outline of the management plan for patients admitted with AAH

Answer 15

1) Treat withdrawal symptoms and seizures if they occur
2) Treat the inflammatory component of AAH
3) Treat any complications of both liver disease and alcohol use
4) Treat malnutrition/malabsorption
5) Abstinence

Question 16

Treatment (AAH) for malnutrition and behavioural changes (delusions, agitation, confusion)

Answer 16

Sedatives and vitamin supplement
- e.g. Chlordiazepoxide (BZ) + Pabrinex (injection)

Chlordiazepoxide

• anti-convulsant and sedative
• slow onset means lower risk of dependency
• symptom triggered dosing
• if chronic end stage patients, give oxazepam/lorazepam (shorter t1/2)

Question 17

Why might shorter-acting BZs be used?

Answer 17

BZs are metabolised by the liver

- effects may last much longer than desired

Question 18

Why is Pabrinex used?

Answer 18

Many patients will have poor diet

• vitamin deficient (high carbs, low protein, vitamins and minerals)
• malabsorption in intestinal mucosa (corrosion of lining)
• thiamine deficiency (vitamin B = polyneuritis- motor/sensory effects)

Question 19

What can thiamine deficiency lead to?

Answer 19

1) Wernicke’s encephalopathy (mimics dementia)
- vitamin B reserves used up
- leads to nstagmus (involuntary rapid eye movements), ataxia (loss control of body movements), learning/memory impairment

2) Korsakoff syndrome

Question 20

Dosing for Pabrinex?

Answer 20

1-3 pairs BD/TDS

• Avoid IM if coagulopathic
• IV also available

Question 21

What are the typical signs of acute alcoholic hepatitis?

Answer 21

Signs of decompensation
Enlarged liver (hepatomegaly)
Fever
Leucocytosis (increased WBC)

Question 22

Lab signs of AAH

Answer 22

Increased:
WBC
Neutrophil count
AST
INR
Bilirubin

Question 23

If signs indicate AAH, but also raised creatinine?

Answer 23

Hepato-renal syndrome

- indication for liver transplant (poor prognostic marker)

Question 24

Scoring systems used for AAH

Answer 24

MELD
Lille

• albumin, bilirubin, INR, creatinine
• recalculate as treatment progresses

Question 25

Pharmacological treatment for AAH

Answer 25

1) Pabrinex/Chlordiazepoxide
2) Corticosteroids e.g. prednisolone 7 days/ pentoxifylline (inhibits TNFa, phosphodiesterase inhibitor)

NB: Pentoxifylline: less evidence based, more experience based for prescriber

Currently in clinical trials:

• anti-TNF biologics
• antioxidants
• colchicine etc.

Question 26

What systems does alcohol effect and how?

Answer 26

Dysregulation GABA + Glutamine

GABA system

• normally, facilitates GABAergic neurotransmission, leading to inhibition
• chronically: body adapts and reduces GABA receptors to counteract alcohol-induced increase in activity

Endogenous opioid system (dopamine)
- increases release of endorphins to stimulate dopamine release

Glutamine system

• inhibits excitatory glutaminergic function
• chronically: upregulated NMDA receptors to increase glutamate functioning

Question 27

What happens if alcohol is suddenly withdrawn?

Answer 27

CNS hyperactivity

- can lead to seizures

Question 28

Treatment for abstinence?

Answer 28

1) Psychological treatments (counselling, therapy)

2) Pharmacological treatment
- Acamprosate
- Disulfram
- Naltrexone (opioid antagonist)

Question 29

What is the mechanism of Acamprosate?

Answer 29

1st line treatment

• stimulates GABAergic neurotransmission
• antagonise effects of excitatory amino-acid neurotransmission
• no liver metabolism nor sedation

Question 30

What is the mechanism and profile of Disulfram?

Answer 30

Irreversibly inhibits aldehyde dehydrogenase

• increased levels of acetaldehyde exacerbate the effects of alcohol, causing patient to refrain from further alcohol intake
• nausea, flushing, headache, palpitations
• metabolised by liver, excreted by kidneys

Benefit is debatable, and relies on patient being compliant

Question 31

What are the significant interactions with disulfram?

What are the ADR’s associated with disulfram?

Answer 31

Phenytoin

Hepatotoxicity

Question 32

What is the mechanism and profile of Naltrexone?

Answer 32

Opioid antagonist

• decrease the affects of alcohol (causes increased opioid activity)
• reduce craving and consumption
• metabolised liver; excreted kidneys
• ADR: hepatoxocity