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MBBS VI - SpC - Medicine > GI - Liver transplant > Flashcards

GI - Liver transplant Flashcards

1
Q

Causes of acute liver failure

A

→ Viral hepatitis
→ Drug-induced, eg. paracetamol, halothane, isoniazid
→ Herbs and health food products
→ Metabolic, eg. pregnancy, Reye syndrome, Wilson’s disease
→ Cardiovascular, eg. shock, heatstroke

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2
Q

Acute liver failure

Cardiovascular manifestations and treatment

A

Hypotension - monitor, echocardiogram

Intravascular volume depletion - fluid resuscitation

Vasodilation - Vasopressors

Low CO and RV failure - Inotropic support

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3
Q

Acute liver failure

Respiratory manifestations and treatment

A

Acute lung injury and ARDS
Higher risk of aspiration pneumonitis

Oxygen support, early tracheal intubation, mechanical ventilation

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4
Q

Acute liver failure

Metabolic and renal manifestations
Treatment

A

Hypoglycaemia - serial biochemical test and glucose supplement

Hyponatremia - fluid management

Renal dysfunction, lactic acidosis, hyperammonemia - renal replacement therapy

Impaired drug metabolism - review drugs

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5
Q

Acute liver failure

CNS manifestations and treatment

A

Hepatic encephalopathy

  • neurological exam, serum ammonia, EEG and psychomotor test
  • Lactulose, rifaximin, BCAA, LOLA
  • Endotracheal intubation if high-grade encephalopathy

Cerebral edema and intracranial hypertension

  • Osmotherapy by mannitol, hypertonic saline
  • Temperature control
  • Rescue therapy - Indomethacine, thiopentone

Seizures: phenytoin or short-acting benzodiazepines

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6
Q

Define the pertinent features of stages of Hepatic encephalopathy

A

0: Normal consciousness, no clinical features, normal EEG
1: Inverted sleep pattern, confusion, euphoria + tremor, apraxia + normal EEG
2: Lethargic, Disinhibition + Flapping tremor, hyporeflexia, dysarthria + Slow EEG
3: Arousable, incoherent speech + Flapping tremor, Hyperreflexia, Babinski + Abnormal EEG
4. Coma, not arousable + Decerebrate position + Abnormal EEG

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7
Q

Outline the King’s criteria for liver transplant for acute liver failure

A

Acetaminophen:

  • pH < 7.3 or all 3 of following
  • Grade III, IV encephalopathy + PT > 100s/ INR > 6.5 + Serum creatinine >300

Non-acetaminophen:

  • PT > 100s/ INR > 6.5 or ANY 3 of following
  • Age under 10 or over 45
  • NOT hepatitis A or B, halothane, idiosyncratic drug reaction, Wilson’s disease
  • Period of jaundice to encephalopathy > 7 days
  • PT > 50s/ INR > 3.5
  • Serum bilirubin > 300
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8
Q

Liver transplant for fulminant liver failure

Indications

A

Indications:

  1. Liver failure:
    - acute liver failure
    - acute-on-chronic liver failure
    - chronic liver failure with worsening liver function (INR, bilirubin, albumin) and cirrhotic complications
  2. Metabolic diseases, eg. haemochromatosis, Wilson’s disease
  3. Small, unresectable HCC:
    → Not meeting hepatectomy criteria: unilobar, no portal vein invasion, no distant mets, 15min ICG retention >14%
    → Meeting UCSF criteria: single ≤6.5cm or max 3 each ≤4.5cm with total ≤8cm
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9
Q

Liver transplant for fulminant liver failure

Contraindications

A

Contraindications:
□ Acute liver failure with uncontrolled infection, Cerebral edema with coning

□ Unfit patient status: severe cardiopulmonary disease, AIDS, uncontrolled sepsis

□ Extra-hepatic malignancy: metastatic HCC or other incurable extrahepatic malignancies

□ Active alcohol or other substance misuse

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10
Q

Define acute-on-chronic liver failure

A

Acute hepatic insult resulting in jaundice (serum bilirubin > 90) and coagulopathy (INR > 1.5)

Complicated in 4 weeks by ascites and/or encephalopathy

In a patient previously diagnosed or undiagnosed with chronic liver disease

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11
Q

List complications of liver cirrhosis

A
  • HCC
  • Portal hypertension: Hypersplenism, esophageal varices, ascites and SBP, hernia and hydrocele
  • Liver dysfunction: Hepato-pulmonary syndrome, Hepato-renal syndrome, Bleeding tendency, Immunosuppression, Malnutrition, Encephalopathy, jaundice
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12
Q

Indication for liver transplant in chronic liver failure

A

Worsening liver function:

  • High INR
  • High bilirubin
  • Low albumin

Complications of cirrhosis appear

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13
Q

2 major Prognostic indices for transplantation

A

□ Model for end-stage liver disease (MELD)

□ Child-Pugh score

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14
Q

Interpret following biochemical pattern for most likely cause of liver failure

 Very high aminotransferase (>3500IU/L)
 Low bilirubin (anicterus in early stages)
 High INR

A

Paracetamol poisoning

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15
Q

Interpret following biochemical pattern for most likely cause of liver failure

 Very high aminotransferase (25-250× ULN)
 Elevated serum LDH

A

Ischemic liver injury

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16
Q

Interpret following biochemical pattern for most likely cause of liver failure

 Coombs-negative haemolytic anaemia
 Aminotransferase <2000IU/L, AST:ALT >2
 Rapidly progressive renal failure
 Low uric acid levels

A

Wilson disease

Note that neurologic WD may be confused with HE. Features suggestive of neurologic WD including presence of dysarthria, dystonia, tremors or Parkinsonism

17
Q

Interpret following biochemical pattern for most likely cause of liver failure

 High aminotransferase (1000-200IU/L)
 ALT > AST levels
 HBsAg+, IgM anti-HBc+

A

Fulminant hepatitis B

18
Q

First-line investigations for acute liver failure

A

Blood:
→ Basics: CBC, RFT, ABG, arterial ammonia
→ Liver panel: LFT, PT/INR, (factor V)
→ Toxicology: serum paracetamol, blood/urine toxicology
→ Viral serology: anti-IgA IgM, HBsAg, IgM anti-HBc, IgM anti-HEV (esp if pregnant), anti-HSV, anti-VZV, IgM anti-CMV, monospot test
→ Autoimmune serology: ANA, anti-smooth muscle, anti-LKM, anti-SLA, Ig pattern

□ Imaging: USG for Budd-Chiari syndrome, portal hypertension, hepatic steatosis

□ Transjugular liver Bx if still unknown cause (percutaneous C/I due to bleeding risk)

19
Q

Child-Pugh score and classification

  • Define metrics measured for total score
  • Function
  • Any use for transplantation?
A

Considers HE, ascites, bilirubin, albumin and PT/INR

Predict prognosis from class A to C

NOT used for transplantation because

  • Limited differentiation: only 8 levels between Child B and C with same scores for different bilirubin and encephalopathy severity
  • Subjective assessment in ascites and encephalopathy
  • Variability of PT/albumin in different labs
20
Q

MELD score

  • Define metrics measured for total score
  • Function
  • Any use for transplant?
A

Based on bilirubin, INR and serum Cr

Excellent in predicting 3mo mortality

Clinically important for prioritization of chronic liver disease patients for transplant

  • ≤14 → does NOT benefit from LT
  • 15-17 → equivocal benefit
  • ≥18 → definitely beneficial
21
Q

Pre-liver transplantation evaluations

A

□ ABO/Rh blood typing: only require ABO matching, does NOT require HLA matching

□ Serology for viral: CMV, EBV, varicella, HIV, hep A-C

□ Cardiopulmonary evaluation: ECG, cardiac stress testing, echocardiogram, lung function test

□ Cancer screening: CT/MRI abdomen, colonoscopy, Pap smear, mammography, PSA as indicated

□ Hepatic imaging: triphasic contrast CT abdomen for vascular anatomy and HCC

□ Upper endoscopy if previous variceal haemorrhage

22
Q

2 sources of liver for transplantation

A

Living donor liver transplant (LDLT)

Deceased donor liver transplant (DDLT)

23
Q

Pre-requisites for Living donor liver transplant

A

 Age 18-60y (arbitrary, depends on LFT)

 No HBV, HCV, HIV infection

 No medical diseases

 Altruistic (ensure informed consent)

 Remnant liver ≥30% of total liver vol

 Remnant liver regenerates to almost 100% within 3mo (otherwise danger)

24
Q

Pre-requisites for deceased donor liver transplant

A

 Brainstem death
 No HBV, HCV, HIV infection*
 No extracranial malignancy

*HIV-positive graft livers may be considered in HIV-positive recipients

25
Q

Living donor liver transplant (LDLT)

  • define differences between transplant to child or to adult
A

Liver is divided by the Cantlie’s line (i.e. from IVC to gallbladder, Middle hepatic vein as landmark)

Left lobe (1/3) transplantation
 For adult to child (left lat. segment)
 From large body sized adult to small body sized adult (<60kg)

Right lobe (2/3) transplantation
 For adult to adult
 Right liver graft with middle hepatic vein
 ↑risk for donor but ↑recipient survival

26
Q

Deceased donor liver transplant

  • Procedures to extract, preserve and insert liver
A

Organ procurement operation
 In situ flushing by cannulating IMV or aorta and pour in preservation solution (HTK solution) at 4oC
 Total hepatectomy of graft liver

Organ transplantation operation
 Usually orthotopic
 Total hepatectomy of diseased liver
 Orthotopic placement of graft liver with anastomosis of suprahepatic/infrahepatic IVC, portal vein, hepatic artery and bile duct

27
Q

Living donor liver transplant

Recipient benefits and costs

A

Recipient benefits:

  • Life saving (5y survival of 85%)
  • Life improvement
  • Earlier and planned operation
  • Healthy graft

Cost:
- Small-for-size graft

28
Q

List donor morbidities after living donor liver transplant

A

Surgical:
- Scar, wound infection, hemorrhage, Pressure ulcer, DVT and PE

Liver:
- Cholestasis, Biliary injury, Portal hypertension

Social:
- Financial (missed work, missed school…)

29
Q

Deceased donor liver transplant

Possible complications?

A

Technical complications
 Bleeding
 Reperfusion injury due to accumulated toxins in GI → endotoxaemia and ↓BP
 Air embolism
 Anastomotic stenosis
 Graft failure due to eg. poor anastomosis, long cold ischaemia time

30
Q

Liver transplant early complications

A

Primary graft non-function: hepatocellular dysfunction due to prolonged cold-ischaemia time

Anastomotic complications
→ Eg. hepatic artery thrombosis, portal vein thrombosis, biliary leak or strictures

Acute cellular rejection: first 5-10d, but can occur at any point after LT (usu ≤6w)

Infection: post-operative bacterial infections, opportunistic pathogens due to high-dose immunosuppression

31
Q

Causative pathogens of post-liver transplant infections

A

0-1mo: post-operative bacterial infections, eg. abdominal/intrahepatic abscesses, cholangitis, wound infection, pneumonia, C. diff colitis

1-6mo: opportunistic pathogens due to high-dose immunosuppression
e.g. CMV, varicella-zoster, Epstein-Barr, RSV, HHV-6, TB

> 6mo: usually with community-acquired infections

32
Q

Late complications after liver transplant

A

Recurrence of primary liver disease: most commonly HBV and HCV

Immunosuppression-related complications:
→ Infections
→ Metabolic syndrome
→ CNI-related renal impairment
→ Metabolic bone disease
→ De novo malignancy: most commonly skin cancer (0.9-3.2%)
→ Hyperuricaemia and gout: ↓uric acid excretion by CyA and tacrolimus

33
Q

Post-liver transplant management

A

Immunosuppressants: usu prefer tacrolimus ± steroids

Antimicrobials: antibiotics, anti-fungal and anti-viral

34
Q

Antimicrobial prophylaxis after liver transplant

Types of drugs used against selective pathogens?

A

→ CMV prophylaxis: valacyclovir, acyclovir

→ PCP prophylaxis: septrin, inhaled pentamidine

→ Antifungal prophylaxis: fluconazole

→ Hepatitis B antiviral if anti-HBc +ve

35
Q

List 5 classes of immunosuppressants with examples for post-liver transplant

A

Calcineurin inhibitor (CNI): cyclosporine, tacrolimus

Steroids (avoid if possible): hydrocortisone, prednisone, prednisolone

mTOR inhibitors: everolimus

Antimetabolites: eg. MMF

Antibody therapy: anti-thymocyte globulin, muromonab-CD3 (OKT3, anti-CD3), basiliximab, daclizumab (anti-IL-2)

36
Q

Side effects of mTOR inhibitors

A

mTOR inhibitors: everolimus

S/E:
↑risk of hepatic artery thrombosis, should NOT be used <30d post-LT;
hyperlipidaemia (for sirolimus)

37
Q

Side effects of anti-metabolites

A

Antimetabolites: eg. MMF

S/E: leukopenia

MBBS VI - SpC - Medicine (80 decks)

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