GI - Liver transplant Flashcards
Causes of acute liver failure
→ 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
Acute liver failure
Cardiovascular manifestations and treatment
Hypotension - monitor, echocardiogram
Intravascular volume depletion - fluid resuscitation
Vasodilation - Vasopressors
Low CO and RV failure - Inotropic support
Acute liver failure
Respiratory manifestations and treatment
Acute lung injury and ARDS
Higher risk of aspiration pneumonitis
Oxygen support, early tracheal intubation, mechanical ventilation
Acute liver failure
Metabolic and renal manifestations
Treatment
Hypoglycaemia - serial biochemical test and glucose supplement
Hyponatremia - fluid management
Renal dysfunction, lactic acidosis, hyperammonemia - renal replacement therapy
Impaired drug metabolism - review drugs
Acute liver failure
CNS manifestations and treatment
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
Define the pertinent features of stages of Hepatic encephalopathy
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
Outline the King’s criteria for liver transplant for acute liver failure
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
Liver transplant for fulminant liver failure
Indications
Indications:
- Liver failure:
- acute liver failure
- acute-on-chronic liver failure
- chronic liver failure with worsening liver function (INR, bilirubin, albumin) and cirrhotic complications - Metabolic diseases, eg. haemochromatosis, Wilson’s disease
- 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
Liver transplant for fulminant liver failure
Contraindications
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
Define acute-on-chronic liver failure
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
List complications of liver cirrhosis
- 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
Indication for liver transplant in chronic liver failure
Worsening liver function:
- High INR
- High bilirubin
- Low albumin
Complications of cirrhosis appear
2 major Prognostic indices for transplantation
□ Model for end-stage liver disease (MELD)
□ Child-Pugh score
Interpret following biochemical pattern for most likely cause of liver failure
Very high aminotransferase (>3500IU/L)
Low bilirubin (anicterus in early stages)
High INR
Paracetamol poisoning
Interpret following biochemical pattern for most likely cause of liver failure
Very high aminotransferase (25-250× ULN)
Elevated serum LDH
Ischemic liver injury
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
Wilson disease
Note that neurologic WD may be confused with HE. Features suggestive of neurologic WD including presence of dysarthria, dystonia, tremors or Parkinsonism
Interpret following biochemical pattern for most likely cause of liver failure
High aminotransferase (1000-200IU/L)
ALT > AST levels
HBsAg+, IgM anti-HBc+
Fulminant hepatitis B
First-line investigations for acute liver failure
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)
Child-Pugh score and classification
- Define metrics measured for total score
- Function
- Any use for transplantation?
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
MELD score
- Define metrics measured for total score
- Function
- Any use for transplant?
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
Pre-liver transplantation evaluations
□ 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
2 sources of liver for transplantation
Living donor liver transplant (LDLT)
Deceased donor liver transplant (DDLT)
Pre-requisites for Living donor liver transplant
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)
Pre-requisites for deceased donor liver transplant
Brainstem death
No HBV, HCV, HIV infection*
No extracranial malignancy
*HIV-positive graft livers may be considered in HIV-positive recipients
Living donor liver transplant (LDLT)
- define differences between transplant to child or to adult
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
Deceased donor liver transplant
- Procedures to extract, preserve and insert liver
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
Living donor liver transplant
Recipient benefits and costs
Recipient benefits:
- Life saving (5y survival of 85%)
- Life improvement
- Earlier and planned operation
- Healthy graft
Cost:
- Small-for-size graft
List donor morbidities after living donor liver transplant
Surgical:
- Scar, wound infection, hemorrhage, Pressure ulcer, DVT and PE
Liver:
- Cholestasis, Biliary injury, Portal hypertension
Social:
- Financial (missed work, missed school…)
Deceased donor liver transplant
Possible complications?
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
Liver transplant early complications
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
Causative pathogens of post-liver transplant infections
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
Late complications after liver transplant
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
Post-liver transplant management
Immunosuppressants: usu prefer tacrolimus ± steroids
Antimicrobials: antibiotics, anti-fungal and anti-viral
Antimicrobial prophylaxis after liver transplant
Types of drugs used against selective pathogens?
→ CMV prophylaxis: valacyclovir, acyclovir
→ PCP prophylaxis: septrin, inhaled pentamidine
→ Antifungal prophylaxis: fluconazole
→ Hepatitis B antiviral if anti-HBc +ve
List 5 classes of immunosuppressants with examples for post-liver transplant
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)
Side effects of mTOR inhibitors
mTOR inhibitors: everolimus
S/E:
↑risk of hepatic artery thrombosis, should NOT be used <30d post-LT;
hyperlipidaemia (for sirolimus)
Side effects of anti-metabolites
Antimetabolites: eg. MMF
S/E: leukopenia
