Liver II

Question 1

LFTs

Answer 1

• NB- exact reference ranges vary depending on the lab
• ALT (7-55 IU/L)- tell you about a primary liver problem
• AST (8-48 IU/L)- Indicate liver damage (released from hepatocytes)- in cirrhosis you have fewer hepatocytes so don’t produce many enzymes (why it is not that high)
• ALP (45-115 IU/L)- Billary disease
• Albumin (35-50g/L)- tell you about a primary liver problem- tends to be chronic liver disease
• GGT (9-48 IU/L)- Inducible enzyme (tends to be alcohol)
• Bilirubin (<19micromol/L)- raised in biliary disease (struggle to get rid of bile)
• INR (approx 1 (2.5 on warfarin)- tell you about a primary liver problem - no clotting factors
  
  • INR goes up Billary disease- bile absorbs fat vitamins (K) which are needed for clotting

Question 2

Prescribing in liver disease

Answer 2

• Primarily liver on biliary disease
• Pattern of LFTs
• Diagnosis
• Severity of disease
  
  • Child-Pugh classification
  • MELD/PELD
  • UKELD

Question 3

Child Pugh classification

Answer 3

Question 4

Drug considerations

Answer 4

• Liver metabolised
• Biliary excretion
• Other pharmacokinetic properties
  
  • Plasma binding
  • Extraction ratio
  • 1st pass metabolism & portosystemic shunts
• Consequences of accumulation (toxicity)
• Indication
• Alternatives

Question 5

General prinicples

Answer 5

• Avoid drugs which cause sedation if possible- cover encephalopathy
• Avoid NSAIDs- Risk of bleeding
• Avoid nephrotoxic drugs- Hepato-renal syndrome
• Consider starting low dose & titrate if appropriate-

Question 6

Indications for liver transplantation

Answer 6

Question 7

Contraindication to LTx

Answer 7

• Extra-hepatic malignancy
• Significant co-morbidity
• Active infection/sepsis
• Severe anatomic deviation- SMV thrombosis
• Active alcohol/ drug user

Question 8

Types of liver donors

Answer 8

• Donation after brain death (DBD)
• Donation after circulatory death (DCD)
• Living donor liver transplantation (LDLT)

Question 9

Types of liver graft

Answer 9

• Full size liver
• Partial graft- split liver
• Domino liver
• Auxiliary graft

Question 10

Split liver grafts

Answer 10

• Introduced in 1988
• For two recipients
  
  • Adult and child
  • Possibly for 2 adults

Question 11

Early complications after liver transplant

Answer 11

• Bleeding
• Hepatic artery thrombosis
• Primary non-function
• Acute renal failure
• Acute rejection
• Biliary obstruction/Leakage/Cholangitis
• Bacterial and opportunistic infection
• (Viral and fungal)

Question 12

Treatment of rejection

Acute

Answer 12

• Organ dysfunction elevated LFTs, unwell patient
• Biopsy (US to exclude vascular complications)
• Treatment with a pulse of steroids (prednisolone 200mg/ methylprednisolone 1g for 3 days)
• Check patient’s compliance
• Usually within 6 months of LTx

Question 13

Treatment of rejection

Chronic

Answer 13

• Slow organ function loss
• Difficult to treat
• Rare with new immunosuppressive drugs ( compliance )

Question 14

Late complications after LTx

Answer 14

• Recurrent diseases
  
  • Hepatitis C, PSC, PBC, HCC
• Biliary strictures
• Malignancy
• Chronic rejection

Question 15

Cause of death >5 years

Answer 15

• CV mortality
• New malignancy
• Sepsis
• Renal failure
• Chronic rejection

Question 16

Late outcome issues- how important?

Answer 16

• Limited number of donor livers
• Rising demand
• Rising mortality on LTx waiting list
• Maximum return needed on each donor
• Greatest need versus greatest benefit

Question 17

Medication post-transplant

Answer 17

• Immunosuppression
• Prevention of infection
• Gastro-protection
• Analgesia
• Prevention of hepatic artery thrombosis

Question 18

History of immunosuppression

Answer 18

Question 19

Liver transplant anti-rejection medication

Tacrolimus

Answer 19

Question 20

Liver transplant anti-rejection medication

Mycophenolate

Answer 20

Question 21

Liver transplant anti-rejection medication

Azathioprine

Answer 21

Question 22

Liver transplant anti-rejection medication

Prednisolone

Answer 22

Question 23

Other possible long term medications

Answer 23

Question 24

Short term medications following liver transplant

Answer 24

• Lanzoprazole- GI protection- decrease acid production
• Nystatin- prevent oral thrush
• Co-trimoxazole- Antibiotic- prevent chest infections
• Valganciclovir- Prevent CMV infection
• Isoniazid- Prevent TB
• Pyridoxine- Prevent pins and needles caused by isoniazid
• Sodium Bicarbonate- lower potassium in the blood
• Paracetamol- Analgesia
• Tramadol- Analgesia

Question 25

Information for patients taking tacrolimus

Answer 25

• The dose of tacrolimus is carefully adjusted to individual patients needs: too much (toxicity) too little (rejection of graft)
• Some medicines will interact with tacrolimus so you should always check new medications (OTC + Herbal)
• Some of the more commonly taken medicines interact with tacrolimus
  
  • NSAIDs
  • Antibiotics: Macrolides, rifampicin, chloramphenicol
  • CCB: Nicardipine, nifedipine and diltiazem
  • Antifungals: fluconazole, ketoconazole, miconazole, caspofungin
  • Drugs for HIV
  • Diuretics: Amiloride etc
  • Others: Omeprazole, StJW
  • Grapefruit juice, earl grey tea, herbal meds

Question 26

Role of pharmacist

Counselling of patient

Answer 26

• Reason for medication, dose, how to take
• SE
• Monitoring
• DDI
• COMPLIANCE

Question 27

Role of pharmacist

F/U in clinic

Answer 27

• Compliance
• Further Pt education
• Rx amendments
• Long-term meds

Question 28

Role of pharmacist

Clinical screening of prescriptions

Answer 28

• Usual clinical screen, plus:
• Adherence to Tx protocols
• Amendment of doses according to levels, renal fn et
• DDI

Question 29

Role of pharmacist

Others

Answer 29

• Prescribing
• Advice on prescribing in liver disease (pre-LTx)
• DH pre-LTx- what should be stopped post-Tx, what continued

Question 30

Normothermic machine perfusion

Answer 30

• New technique enabling real-time organ viability and function assessment
• Minimise organ damage during the preservation time
• Potential to increase organ number by 10-30%