Hepatobiliary Surgery JC066: I Need A New Liver: Liver Transplantation Flashcards
Questions related to liver transplantation
- What are disease indications for liver transplantation?
- When should liver transplantation be performed?
- What are sources of liver graft?
- How is it being performed?
- What are the post-operative complications and medications?
- How successful is liver transplantation in the long run?
Indications for liver transplantation
- Fulminant hepatic failure
- Acute-on-chronic liver failure
- Chronic liver failure
- Metabolic diseases
- Small unresectable HCC
- Fulminant hepatic failure
- Severe liver injury, potentially reversible in nature with onset of hepatic encephalopathy **within 8 weeks of first symptoms (usually jaundice) in **absence of pre-existing liver disease
Causes:
1. Drug intoxication
- paracetamol
- halothane
- Food poisoning
- Amanita phalloides (mushroom) - Hepatitis
- Hep A, E
- Acute Hep B - Wilson’s disease
Clinical features of Acute hepatic failure
Clinical features:
1. Brain
- hepatic encephalopathy
- cerebral edema
- intracranial hypertension
- Lung
- acute lung injury - Liver
- loss of metabolic function
- hypoglycaemia
- lactic acidosis
- hyperammonaemia
- coagulopathy - BM
- suppression - Leukocytes
- impaired function —> high risk of sepsis - Heart
- high output state - Pancreas
- pancreatitis - Adrenal
- inadequate glucocorticoid production —> hypotension - Kidney
- dysfunction / failure - Portal hypertension
- Systemic inflammatory response
Management of Acute liver failure
Nursed in ***ICU
1. Organ support
- ***Metabolic support
- hypoglycaemia
- hypoNa - Monitor consciousness level
- indication for liver transplantation - ***Coagulopathy
- beware of procedures - ***Antibiotic prophylaxis
Hepatic encephalopathy
- may progress ***rapidly within days
- monitor closely + protect airway
Grading (0-4) on 3 aspects:
1. Consciousness / Intellect
- forgetfulness, irritability (grade 1)
- lethargic (grade 2)
- somnolent, aggressive (grade 3)
- coma (grade 4)
- Clinical features
- apraxia (grade 1)
- flapping tremor (grade 2)
- babinski +ve (grade 3)
- decerebrate (grade 4) - EEG
- slow 5 cps triphasic waves (grade 1-3)
- slow 2-3 cps delta waves (grade 4)
Subclinical (between 0 and 1): Normal Consciousness / Intellect + EEG except Psychomotor testing abnormality
Indication for Liver transplantation
King’s college criteria
- Irrespective of grade of encephalopathy
- PT >100s (INR >6.5)
or 3 of following:
- Age <10 / >40
- Duration of jaundice before encephalopathy >7 days (indicate low reversibility)
- PT > 50s (INR >3.5)
- Bilirubin > 300 umol/L
- Non-A, Non-B, Halothane or Idiosyncratic drug reaction, Wilson’s disease
For paracetamol poisoning:
- pH <7.3
or
- PT >100 + Creatinine >300 + Grade 3/4 encephalopathy
When NOT to transplant in Acute liver failure
- ***Uncontrolled infection
- e.g. severe bronchopneumonia, fungal septicaemia - Cerebral edema + ***coning
- may become vegetative state even after operation
Acute-on-chronic liver failure
Acute hepatic insult manifesting as:
- **Jaundice (serum bilirubin >90) + Coagulopathy (INR >1.5)
- Complicated within 4 weeks by **Ascites / Encephalopathy in a patient with ***previously diagnosed / undiagnosed chronic liver disease
Causes:
- Acute exacerbation / Flare of chronic Hep B
- Cirrhosis with acute deterioration
—> hepatic function ***decompensation (e.g. variceal bleeding)
—> death
Chronic liver failure
Causes:
- Cirrhosis (of any etiology)
—> **Hep B
—> **Hep C
—> **Alcoholism
—> **Primary biliary cirrhosis
—> Secondary biliary cirrhosis (chronic bile duct obstruction due to iatrogenic disease, biliary atresia in paediatrics —> ***longstanding biliary obstruction)
—> Autoimmune hepatitis
—> Budd-Chiari syndrome
***Clinical features of Chronic liver failure
- Malaise
- Jaundice
- Ascites
- Infection (spontaneous bacterial peritonitis)
- Bleeding esophageal varices
- Coma
Laboratory abnormalities:
1. ↑ INR
2. ↑ Bilirubin
3. ↓ Platelet
4. ↓ Serum albumin
5. ↓ WBC (∵ hypersplenism)
(6. ↑ NH3, ↓ Urea)
Complications of Cirrhosis
- HCC
- Portal hypertension
- Varices in stomach, esophagus —> Bleeding
- **Ascites —> Infection (spontaneous bacterial peritonitis) + Hernia, Hydrocele
- **Hypersplenism
- ***Encephalopathy - Liver dysfunction
- **Hepatopulmonary syndrome (↑ liver production / ↓ liver clearance of vasodilators, possibly involving nitric oxide —> **microscopic intrapulmonary arteriovenous dilatations —> **overperfusion relative to ventilation, leading to **VQ mismatch + hypoxemia)
- Ascites —> Infection (spontaneous bacterial peritonitis) + Hernia, Hydrocele
- ↓ Protein synthesis —> Malnutrition, **Immunosuppression, **Bleeding tendency
- ↓ Elimination of wastes —> **↑ Bilirubin, **Encephalopathy, **Hepatorenal syndrome (∵ activation of **RAAS due to portal hypertension —> renal vasoconstriction)
When to transplant in Chronic liver failure
- Worsening of liver function
- ↑ INR, ↑ Bilirubin, ↓ Albumin
- Complications of cirrhosis (esophageal bleeding, intractable ascites, unresectable HCC, spontaneous bacterial peritonitis)
Sources of donor liver grafts
- Living donor liver transplantation
- Deceased donor whole graft liver transplantation
- Deceased donor split liver transplantation
- Deceased donor reduced size liver transplantation
- Sequential liver transplantation
Demand for liver transplant: 15-20 per million population per year
HK brain dead organ donation rate: 4-6 per million population per year
Diagnosis of brain death
- ***Fixed + dilated pupils, not responding to light
- Absent corneal reflexes
- No motor response to painful stimuli
- No reflex activity except spinal cord reflex
- No oculocephalic reflex (doll’s eyes)
- No vestibulo-ocular reflexes
- No gag / cough reflex to bronchial stimulation
- No respiratory movements if mechanical ventilation stopped to ensure pCO2 >60 mmHg
Prerequisite for Liver donation
- ***No HBV, HCV, HIV infection
- ***No extracranial malignancy
Transplantation procedure
- Brainstem dead patient
- Organ harvesting
- in-situ flushing (to cannulate aorta with cold organ preservation solution)
- **University of Wisconsin solution at 4oC
—> HES (Hydroxyethyl starch): support colloidal pressure
—> Lactobionate: prevent cell swelling
—> Glutathione: inhibit oxygen free-radical generation
—> Adenosine: enhance ATP synthesis after reperfusion
—> Allopurinol: inhibit oxygen free-radical generation
—> others
or
- **HTK solution (Histidine-Tryptophan-Ketoglutarate)
—> little K content (lower chance of cardiac arrhythmia) - Orthotopic liver transplantation: Anastomosis
- Suprahepatic + Infrahepatic IVC
- Hepatic artery
- Portal vein
- Bile duct
- Hepaticojejunostomy / Duct-to-duct anastomosis
Technical complications of Liver transplantation
- ***Bleeding (∵ deranged liver function —> coagulopathy)
- ***Reperfusion injury (flushing of endotoxins, sudden ↑ right heart strain —> right heart failure)
- Air embolism
- Anastomosis stenosis
- ***Graft failure
Who gets the brain-dead organ first?
- According to urgency
- Patients with ***Fulminant liver failure will get first
- Chronic liver failure patients are prioritised according to liver function grading
Liver function grading
- Child-Pugh classification
- MELD (Model for End-stage Liver Disease) score —> **better depictor for mortality
- Serum bilirubin level
- INR
- Serum creatinine level
—> Cut-off value: **>=15 (already shows significant survival benefit)
Liver donation
Full function of liver required: ***>=1/3 of normal liver
Dead donor:
- One Liver will be split into Right + Left lobe for 2 patients
- along Cantlie’s line (middle hepatic vein) (X Falciform ligament: divide Left lateral and Left medial segment)
- Right (2/3 of liver): including RHV + MHV, for Adult
- Left (1/3 of liver): for Young adults / children
Living donor:
Left liver donation:
- From large body size to small body size recipient
- Limited applicability
Right liver donation:
- From small body size to large body size recipient
- Expands applicability of living donor liver transplantation
Living donor liver transplantation (LDLT)
Currently, LDLT and DDLT has comparable outcomes (even for high MELD score —> i.e. no need to wait for deceased donor graft)
Prerequisite:
- <60 yo
- **No HBV, HCV, HIV infection
- **No medical diseases
- Altruistic (no conflict of interest)
- Remnant liver ***>=30% total liver volume (∵ avoid liver failure in donor)
- Remnant liver regenerates to almost 100% in 3 months
Cost and Benefits:
Recipient benefit:
- life saving
- life improvement
- **earlier operation (no need to wait for graft)
- **planned operation
- healthy graft
Recipient cost
- small-for-size graft (smaller than whole graft)
Donor cost:
- mortality ~0.5%
- **morbidity ~15%
—> wound infection, cholestasis, biliary injury, haemorrhage, DVT, PE, pressure ulcer, portal hypertension, scar, financial burden, school
- surgical scar
- **long term morbidity?
Donor benefit:
- satisfaction
Post-op medication for recipients
-
Immunosuppressants (lifelong)
- **IL-2 receptor antagonists (Simulect) (during the operation)
- Steroid
- Cyclosporine, FK506 (Tacrolimus, prone to develop seizure after surgery) (after induction during operation) (Calcineurin inhibitor)
- Sirolimus, Everolimus (anti-tumour effect as well —> for HCC) (mTOR inhibitor)
- **Mycophenolate mofetil (as an adjunct) - Antibiotics
- Antifungals
- Antivirals
Current practice of immunosuppression:
- ***Avoid steroid
- Try to ↓ dosage of immunosuppressants
Risk of immunosuppressants
- ↑ risk of opportunistic **infection
- e.g. CMV, TB - ↑ risk of ***malignancy
- Drug specific **SE
- Steroid: moon face, osteonecrosis, impaired glucose tolerance
- Cyclosporine: **hairy face (hirsutism), **gum hypertrophy, **nephrotoxicity
- Tacrolimus (FK506): **neurotoxicity (idiosyncratic), **nephrotoxicity
- Mycophenolate mofetil: **leukopenia
- Sirolimus: **hyperlipidaemia
From JC077:
1. Prednisolone: Cushingoid facies, **hyperglycaemia, HL, peptic ulcers, HT
2. Cyclosporine: **nephrotoxicity, HT, HL, **gum hypertrophy, gout
3. Tacrolimus: **nephrotoxicity, HT, **new onset DM, tremors, GI upsets
4. Mycophenolate mofetil: diarrhoea, vomiting, **anaemia, **leukopenia, viral infections
5. Rapamycin: synergistic nephrotoxicity with CNIs, proteinuria, HL, impaired wound healing, interstitial pneumonitis
6. Azathioprine: GI upsets, **hepatotoxicity, anaemia, leukopenia, thrombocytopenia
Long-term outcome of Liver transplantation
- 5-year survival 85%
- Good QOL
- Gainful employment
- ***Recurrence of original disease (e.g. HCC) possible
- ***Transmission of disease from donor to recipient possible
Summary
- Improve brain-dead donor organ donation rate
- Use every liver graft (even HBV e.g. HBV donor to HBV recipient) / Split into 2 grafts
- Explore possibility of Non-heart beating donor
- Improve donor safety
- Improve recipient survival
- Audit and Research
SpC Interactive tutorial: Portal Hypertension
Portal hypertension:
- Pathologic increase in portal pressure
- Resulting from obstruction of portal blood draining from splanchnic circulation back to systemic circulation
Normal direction of flow splanchnic circulation:
- Left gastric vein (aka Coronary vein) + Splenic vein + Inferior mesenteric vein
—> join Superior mesenteric vein
—> Main portal vein
—> R + L portal vein
—> Liver
—> R + M + L Hepatic vein —> IVC
- Short gastric vein / Vasa brevia —> Lower esophagus —> Systemic circulation
Definition of Portal hypertension
Pathologic increase in portal pressure
***Portal pressure gradient (PPG): >5 mmHg
- PPG = Portal vein P - IVC P
- PPG >10mmHg —> Ascites
- PPG >12mmHg —> Variceal bleeding
- PPG 6-10mmHg —> Subclinical portal hypertension (detected in surveillance imaging)
Etiologies of Portal hypertension
- Pre-hepatic (20%)
- **Malignant invasion of portal vein (e.g. **Head of pancreatic cancer, ***HCC)
- Congenital absence of portal vein
- Thrombophlebitis of umbilical vein - Hepatic (80%)
- ***Cirrhosis
—> Viral cirrhosis
—> Alcoholic cirrhosis
—> Autoimmune hepatitis causing cirrhosis
—> PBC, PSC
—> Biliary atresia
—> Wilson’s disease
- Congenital hepatic fibrosis - Post-hepatic
- Cardiac cirrhosis (RH failure e.g. constrictive pericarditis)
- IVC obstruction
- Budd-Chiari syndrome (Hepatic vein obstruction)
- Venule obstruction (i.e. in Sinusoid level) —> Hepatic veno-occlusive disease
***Pathophysiology of Portal hypertension
Cirrhotic liver
—> **Architectural disturbances (fibrosis, scarring, vascular thrombosis inside liver etc.) + **Functional alterations (contraction of vascular smooth muscle + stellate cells)
—> Increased hepatic resistance
—> Portal hypertension
—> **Splanchnic arterial vasodilatation (splanchnic arteries try to dilate to increase blood flow to liver) —> Increased portal blood inflow —> Portal hypertension (vicious cycle)
—> **Effective hypovolaemia (low BP) —> Activation of endogenous vasoactive system —> contraction of vascular smooth muscle (in liver?) —> Portal hypertension (vicious cycle)
—> ***Na retention, Hypervolaemia, Increased cardiac index
—> Increased portal blood flow
—> Portal hypertension (vicious cycle)
Long-term outcome of Portal vein thrombosis
- Cavernous transformation
- New vessel development across blocked portal vein - Collaterals formation
- Pre-existing vessel (usually not engorged / dilated) between portal and systemic circulation —> Engorged + Open during portal hypertension
- Thin wall veins —> cannot support large volume of portal blood flowing through them —> rupture may occur (esp. for varices located at GEJ —> massive bleeding)
- ↑ Variceal wall tension may be cause of rupture
Clinical features of Portal hypertension
Back pressure effect:
Viscera:
- Splenomegaly
- Ascites
- Hepatomegaly (if post-hepatic cause)
Blood vessels:
- Dilatation of pre-existing collaterals between portal and systemic circulation
—> Venous hum
—> Around umbilicus: Caput medusae (∵ umbilical vein join the left portal vein —> normally obliterated after birth)
—> Lower end of esophagus: Esophageal varices
—> Rectum and anal canal: Rectal varices
—> Extraperitoneal / Retroperitoneal surfaces: Silent (seen only on imaging)
Diagnosis of Portal hypertension
- Clinical
- Manifestations of portal hypertension - Measurement of portal pressure
- Cannulation of branch of mesenteric vein at laparotomy
- Wedge hepatic venous pressure (balloon inflated: Portal pressure, deflated: IVC pressure)
- Percutaneous transhepatic cannulation of portal vein (by interventional radiologist)
CT images of Cirrhosis
Liver:
- Shrunken liver: left lateral section not covering stomach, large potential space between liver and anterior abdominal wall (normally no space)
- Nodular surface
- Recannulisation of umbilical vein (pathognomonic)
Spleen:
- Splenomegaly: enlargement beyond mid-axillary line
Esophageal varices
Diagnosis:
1. Barium swallow (obsolete, showing spiral shape filling defect)
2. Upper endoscopy
- 4 columns: 2, 5, 7, 10 o’clock
- no correlation between degree of portal HT and number of columns
- Active bleeding from varices
- Blood clot on varices indicating recent bleeding
- Esophageal varices only and absence of other bleeding source in stomach / duodenum
Clinical features:
1. Haematemesis
2. Melena (Fresh / Old)
3. Shock
4. Hepatic encephalopathy / coma (∵ ↑ nitrogen products)
Treatment aim:
1. Stop bleeding
2. Restore / Maintain normal BP, pulse, urine output, haematocrit —> maintain organ function (including liver)
3. Prevent hepatic coma in case of cirrhosis (∵ blood breakdown product in gut absorbed into portal blood may predispose to hepatic coma)
***Treatment of Esophageal variceal bleeding
- ABC
- ETT intubation if coma / haematemesis clot
- 2 Large bore cannula
- IV fluid + blood replacement (if large blood loss + high rate of loss) - ***Terlipressin / Vasopressin + Nitroglycerin (counteract Vasopressin’s vasoconstriction in heart / gut)
- Upper endoscopy
- active bleeding still seen —> **Sengstaken-Blakemore tube (if you don’t know how to do intervention) / **Injection Sclerotherapy / ***Banding
- active bleeding not seen (i.e. bleeding stopped) —> Continue supportive treatment - Correct bleeding tendency
- **FFP infusion
- **Platelet concentrates infusion - Anti-hepatic coma treatment
- **Lactulose
- **Rifaximin (0% bioavailability —> high concentration in large bowel —> kill all gut flora converting blood products into toxic substance)
- Neomycin (nephrotoxic)
- Enema (rarely used since patient cannot hold enema) - Antibiotic
- ∵ Immunocompromised - Definitive treatment (if not done yet)
- **Injection Sclerotherapy / **Banding - Re-bleeding
- **TIPS
- **Surgery (Shunt, Devascularisation)
- ***Liver transplantation - No re-bleeding
- Reassess by endoscopy every 2 months (***Propranolol (decrease portal BP) +/- Isosorbide mononitrate)
Risk of emergency endoscopic treatment of bleeding varices:
1. Aspiration pneumonia
2. Prolonged hypotension
3. Serious complications (10-20%)
- e.g. Malposition of gastric balloon
4. Procedure related mortality (2%)
Sengstaken-Blakemore tube
- 3 lumens
—> Gastric balloon
—> Esophageal balloon (seldom need to inflate if gastric ballon can already stop bleeding)
—> Gastric aspiration channel - Inflate gastric balloon —> Stop bleeding by compression of GEJ —> Interruption of blood flow from gastric veins to azygos vein
- Inflation of gastric balloon by 200ml
- Traction by 1 pound weight
- NOT exceed ***24 hours
- Efficacy 90%
Problems:
1. Incorrect position of gastric balloon
- Esophagus —> **Perforation of esophagus (causing mediastinitis)
- Trachea —> **Perforation of trachea
- Inadequate traction —> Continue bleeding
- Inadequate size —> Slipping out of esophagus —> **Asphyxia, laceration of esophagus —> 1 pound weight should be <=15 cm from ground (∵ esophagus length is ~25cm)
2. Patient’s saliva cannot empty into stomach —> **Aspiration of saliva into trachea
3. Too heavy + prolonged traction —> ***GEJ necrosis
Confirmation of position of gastric balloon:
1. Plain X-ray
2. Radioopaque contrast in gastric balloon
3. Endoscopy (best way ∵ direct vision)
Medical therapy
- Terlipressin (Vasopressin analogue) (70-75% effective)
- Octreotide (65%)
- Somatostatin (65%)
- Vasopressin (50%)
Vasopressin:
- lower portal BP by constricting splanchnic arterioles
- may induce **Ischaemia to small bowel —> abdominal pain
- may induce **myocardial ischaemia
- ***Nitroglycerin used to counteract vasoconstrictive SE (not advocated now)
Prevent recurrent bleeding after stabilisation
- Injection sclerotherapy / Banding —> Obliteration of esophageal varices
- Via endoscopy
- Fine need puncture of varices / para-variceal areas (no difference)
- Sclerosants: Ethanolamine oleate / Sodium tetradecyl sulphate
- Fibrin glue for gastric varices (not for esophageal varice due to risk of chemical mediastinitis) - Creation of shunt between portal vein (or its branches) to IVC (or its branches) (Radiologically / Surgically) —> Reduction of portal BP
Radiological shunt:
- Transjugular intrahepatic porto-systemic shunt (TIPS) (stenting between hepatic vein and portal vein)
- Risk: HE
Surgical shunt:
- **Total shunt: Porto-caval shunt (all portal blood now go into IVC)
- **Selective shunt: Mesenterico-caval shunt / Spleno-renal shunt (only shunt part of portal blood away —> lower risk of HE / liver atrophy)
- Risks:
—> **Hepatic encephalopathy (∵ nitrogenous products diverted away from liver)
—> **Liver atrophy (∵ gut hormone no longer goes to liver)
- Advantage of selective shunt:
—> Maintain blood supply to liver + prevent liver atrophy / HE
- Division / Detachment of blood vessels around the GEJ (i.e. Devascularisation) —> Reduction of blood flow to stomach + esophagus
- Liver transplantation if liver irreversibly damaged by disease
Choices:
1. Injection sclerotherapy / Banding
- ALL cases
- Surgical shunt
- Recurrence of bleeding after Injection sclerotherapy / Banding
- Child A - Radiological shunt
- Recurrence of bleeding after Injection sclerotherapy / Banding
- In preparation for liver transplantation (∵ anatomy not altered) - Devascularisation
- Recurrence of bleeding after Injection sclerotherapy / Banding
- Child C - Liver transplantation
- Child C
