Unit 4 - The Liver 2

Question 1

What sexual characteristics are affected by liver disease?

Answer 1

Endocrine changes most common in alcoholic liver disease

- poor metabolism of oestrogen

Question 2

How are males affected by liver disease?

Answer 2

Testicular atrophy
Female body hair
Gynaecomastia
- increased breast tissue

Question 3

How are females affected by liver disease?

Answer 3

Menstrual irregularity

Reduced fertility

Question 4

How can liver disease be tested biochemically?

Answer 4

Simple, inexpensive, easy to perform
Useful to monitor disease progression or response to therapy
Enzymes
- hepatocellular
- AST
- ALT
Bilirubin
Synthetic function
- PT and INR
- albumin

Question 5

Apart from biochemical liver tests, how else can liver disease be investigated?

Answer 5

Laboratory investigations
- hepatitis A
- hepatitis B
- hepatitis C
- immunoglobulins
- lipid profile
Imaging
- ultrasound - preliminary assessment
- CT and MRI - precise definition of abnormalities
Biopsy
- gold standard for establishing diagnosis and assessing severity

Question 6

What is the treatment for pruritis?

Answer 6

Anion exchange resins

- bind bile acids and prevent reabsorption

Question 7

What are the side effects of anion exchange resins?

Answer 7

GI issues
- constipation
- diarrhoea
- flatulance
Fat and vitamin malabsorption

Question 8

Why is the poor adherence of anion exchange resins?

Answer 8

Poor palatability

Question 9

What counselling points should be given for treating pruritis?

Answer 9

Take interacting drugs 1 hour before or 4 hours after colestyramine
Benefits may take up to one week to become apparent

Question 10

Give two examples of anion exchange resins used to treat pruritis

Answer 10

Colestyamine

Colestipol

Question 11

Apart from anion exchange resins, what else can be used to treat pruritis?

Answer 11

Antihistamines
- sedating properties useful if pruritis affects sleep
Ursodeoxycholic acid
- treats cholestatic disease
Rifampicin
- inhibits hepatocyte uptake of bile salts
- decreases reabsorption
Opiod antagonists
- itching due to increased endogenous opiate tone
Topical therapies
- calamine lotion
menthol 2% in aqueous cream

Question 12

What is the aim of treating ascites?

Answer 12

Mobilise intra-abdominal fluid

Question 13

What non-pharmacological treatments are there for ascites?

Answer 13

Simple measures:
- reduce sodium intake
- fluid restriction
Moderate to severe measures
- diuresis (increase urine output)
- paracentesis (sucked out with a needle)

Question 14

What pharmacological treatments are there for ascites?

Answer 14

Diuretics
- increase diuresis
Spironalactone is first line agent
- blocks sodium reabsorption in kidney tubules
- dose range 50 - 400 mg daily
- titrate slowly
- side effects
- gynaecomastia (potassium sparing diuretic)
- hyperkalaemia (potassium sparing diruetic)
Add furosemide if severe
Care to avoid excessive diuresis

Question 15

How is paracentesis used to treat ascites?

Answer 15

Use in refractory ascites
Combined with albumin administration
Does not affect mechanisms responsible for fluid accumulation
- transient effect
Repeated every 2 - 4 weeks in outpatient setting

Question 16

What is TIPS?

Answer 16

Transjugular Intrahepatic Portosystemic Shunt

Question 17

Where is the shunt placed in TIPS?

What is a shunt ?

Answer 17

Between hepatic portal vein and systemic circulation
In medicine, a shunt is a hole or a small passage which moves, or allows movement of, fluid from one part of the body to another

Question 18

What are the drawbacks of TIPS?

Answer 18

Prevents recurrence in refractory ascites

Shunt stenosis is common

Question 19

What percentage of patients with cirrhosis develop encephalopathy?

Answer 19

40%

More than half die within a year

Question 20

What are the symptoms of encephalopathy caused by cirrhosis?

Answer 20

Reversible neuropsychiatric condition

• lack of awareness
• altered mental state
• disorientation

Question 21

What are the causes of encephalopathy in cirrhosis?

Answer 21

Portosystemic shunting
Metabolic dysfunction
Alteration of Blood Brain Barrier
Ammonia heavily implicated
- accumulation in CNS

Question 22

What is encephalopathy precipitated by?

Answer 22

GI bleeding
Spontaneous Bacterial Peritonitis (SBP)
Drugs

Question 23

What is the treatment for encephalopathy?

Answer 23

Lactulose

Antibiotics

Question 24

How is lactulose used to treat encephalopathy?

Answer 24

Acidifies colonic contents
- leading to ionisation of nitrogenous products and therefore a reduction in absorption
30 - 40 ml/day titrated to achieve 2 - 3 soft stools per day
Side effects
- bloating
- diarrhoea

Question 25

How are antibiotics used to treat encephalopathy?

Answer 25

Metronidazole reduces ammonia production by GI bacteria

Question 26

What is used to treat clotting abnormality caused by liver disease?

Answer 26

Phytomenadione IV (vitamin K) - 10mg daily for 3 days - oral not as effective as IV (therefore not used) Not effective in patients with significant disease

Question 27

What medications should patients with a clotting abnormality avoid?

Answer 27

NSAIDs Aspirin Anticoagulants

Question 28

What are varices?

Answer 28

Development of weak and leaky vessels

Question 29

What is the treatment for varices?

Answer 29

Shunting of portal blood to systemic circulation - pre-existing vessels dilate - active angiogenesis

Question 30

What is the initial treatment for varices?

Answer 30

Stop immediate bleeding Treat hypovolaemic shock - increase blood volume Aim to prevent recurrent bleeding

Question 31

What medication should be given immediately to treat varices?

Answer 31

Terlipressin (vasopressin analogue) - systemic vasoconstrictor - infused for 2 - 5 days

Question 32

How can varices be prevented?

Answer 32

``` Band ligation Long term non-selective beta-blockers - propanolol - reduced portal hypertension by splenic vasoconstriction - reduced portal blood flow ```

Question 33

What is Acute Liver Failure (ALF)?

Answer 33

Rapid deterioration in liver function in a previously healthy individual

Question 34

What is the most common cause for Acute Liver Failure in the UK?

Answer 34

Paracetamol overdose

Question 35

Why is Acute Liver Failure complicated to manage?

Answer 35

``` Multiple organ systems affected - central nervous system - cardiovascular - renal systems affected Infection and bleeding can be life threatening ```

Question 36

How many paracetamol tablets consumed within 24 hours can result in severe harm?

Answer 36

20 - 30 tablets

Question 37

Why is paracetamol overdose hard to metabolise?

Answer 37

Saturation of glutathione pathway

Question 38

Which chemical is produced in the metabolism of paracetamol when glutathione is exhausted?

Answer 38

NAPQI

Question 39

When does NAPQI cause necrosis of liver and kidney?

Answer 39

When glutathione reserves are less than 30%

Question 40

What is the timeline after paracetamol overdose?

Answer 40

``` 0 - 24 hours - asymptomatic - non-specific signs 24 - 48 hours - right upper quadrant pain - jaundice - deranged bloods - coagulopathy > 72 hours - jaundice - somnolence - liver failure ```

Question 41

What is the result of paracetamol overdose?

Answer 41

Cerebral oedema Shock Sepsis Renal failure

Question 42

What is the treatment for paracetamol overdose in the first 4 hours?

Answer 42

Activated charcoal - mop up GI tract Do not treat with N-ac - wait for paracetamol to be absorbed into the blood to find single paracetamol concentration related to time of ingestion

Question 43

What is the treatment for paracetamol overdose between 4 and 36 hours after ingestion?

Answer 43

N-actylcysteine - almost 100% effective if given within 8 hours - increases glutathione concentration

Question 44

When was legislation introduced to restrict the sale of paracetamol?

Answer 44

1998 - pack size - packaging

Question 45

What was the effect of restricting the sale of paracetamol?

Answer 45

Significant decrease in paracetamol overdose | - Heath hospital still admits 1 patient a week

Question 46

Why do prescribers need to be aware of liver disease in patients?

Answer 46

Impaired drug metabolism - main route of elimination for many drugs - hepatic reserve is large - liver disease must be severe for clinically relevant changes occur - care with rifampicin and fusidic acid

Question 47

What is hypoproteinaemia?

Answer 47

Low levels of protein in the blood | - albumin

Question 48

What are the implications of hypoproteinaemia?

Answer 48

``` Albumin is produced in the liver Affects highly protein bound drugs - low albumin - less albumin binding - increased free drug concentration - exposure to drug increased ```

Question 49

What prescribing considerations are there in patients with liver disease?

Answer 49

``` Impaired clotting - clotting factors synthesised in liver - increased sensitivity to oral anticoagulants Hepatic encephalopathy - many drugs can impair cerebral function - lower awareness - care with - sedative drugs - opioids - diuretics that reduce potassium levels Fluid overload - oedema/ascites exacerbated by drugs that cause fluid retention - NSAIDs - corticosteroids Hepatotoxic drugs - dose related or idiosyncratic - avoid - use with extreme caution ```