I want to be

a

Paediatric

Liver Transplant surgeon

Dr. Beelke D’hondt

MD ( Belgium), FRC Paed Surg (RSA)

Overview 1. Historical Steps

2. Knowledge

3. Skills

4. Passion

5. Aim for perfection

6. Outcomes

7. Future perspectives

Historical Steps • 1963 : Thomas Starzl : first liver transplantation

• 1967 : Thomas Starzl : first successful liver transplantation

• 1968 : Roy Calne : first successful liver transplantation in Europe (DDLT)

• 1979 : FDA approves cyclosporine

• 1983 : National Institutes of Health : consensus conference declares liver

transplantation a valid therapy for ESLD

• 1984 : first reduced-size liver transplantation

• 1987 : UW solution

• 1988 : First split-liver transplant

• 1989 : Tacrolimus introduced into clinical trials

• 1990 : First successful living-related liver transplantation

• 2003 : IGL-1 solution : to replace UW solution

Recent progress

• Technical development

• Progress in pre-operative management

• Progress in peri- and postoperative management

• Progress in immunosuppression

Recent progress : pre-operative management

1. Multidisciplinary approach of the sick child

2. Nutritional support

3. Enteral feedings

4. Control of bleeding esophageal varices

5. Correction of ascites

Recent progress : peri- and postoperative management

1. Anesthesiological expertise of dealing with

extreme sick babies/infants/children

2. Surgeons trained in paediatric surgery

3. Paediatric intensivists with expertise in liver

failure, renal dialysis

Recent Progress in

immunosuppression

• 1st break through : cyclosporin A + steroids : doubled the 1y patient survival rate

• FK 506 (tacrolimus) with small dosage of prednisolone

• FK 506 + anti-IL-2 receptor monoclonal antibodies: no need for steroids , low incidence of acute rejection

• AIM : prope tolerance, steroid free post PLTX evolution

• Downside: increased risk for infections, malignancies

KNOWLEDGE

Indications & Contraindications

of PLTX • Indications

• Relative contra-indications 1. An advanced or partially treated systemic infection 2. Advanced hepatic encephalopathy (grade IV) 3. Severe psychosocial abnormalities. 4. Portal venous thrombosis extending throughout the mesenteric venous system.

• Absolute contra-indications 1. HIV (+) 2. non-resectable extrahepatic malignancy. 3. Uncontrolled systemic sepsis. 4. Irreversible neurological injury 5. Concomitant end-stage organ failure that cannot be corrected by a combined Transplantation

1. Extra-hepatic cholestasis: Biliary atresia

2. Intra-hepatic cholestatic disease : sclerosing cholangitis, Alagille, PFIC

3. Metabolic disease : Cystic fibrosis, a1- anti trypsine deficiency , Wilson’s disease, Crigler-Najjar syndrome,

disorders of the urea cycle, tyrosinemia, inborn errors of the bile acid metabolism, organic acidemia, acid

Lipase defect, oxaluria type I

4. Fulminant hepatic failure

5. Irresectable hepatic malignancy : hepatoblastoma, HCC

Evaluation of the

transplant patient 1. Confirm indication for PLTX

2. Determine the severity of the disease

3. Consider alternative treatments to Tx

4. Exclude contra-indications to Tx

5. Identify active infections and assess Immunological status of the

child

6. Rule out cardiac malformations that might need to be corrected

before Tx

7. Establish a pre-transplant therapeutic plan : immunizations,

nutritional support, dental care, prevention of drug-induced side

effects

8. Inform parents, and patient, on the transplantation procedure and

the post-transplantation period

9. Evaluate social status and logistic issues

Teamwork

The Key to success

Is

Team of Specialists The hospital in which the liver transplant center will be established should have the following departments :

1. Gastro-enterology with endoscopy facility

2. Pediatric/ adult anesthesiology

3. Pediatric/ adult surgery

4. Pediatric/ adult ICU facility

5. Tropical disease

6. Radiology

7. Hematology and blood bank.

8. Pathology.

9. Biochemistry laboratory.

10. Nephrology with hemodialysis and peritoneal dialysis unit.

11. Cardiology

12. Immunology

• Crossmatch

• Monitoring drug level

• Screening antibodies for patients in waiting list

• HLA typing

•

13. Pneumology

14. Psychiatry

15. Physiotherapy

16. Microbiology laboratory

• PCR- EBV

• CMV Antigen

HOLISTIC APPROACH

Mens sana in corpore sano

Child = sick kid

• Kiddie with a (congenital) disease

• Malnourished

• Unhappy miserable desperate

• Family member

Prioritization

• Early 80ies : patient stratification based on

severity of illness & waiting time

• Late 80ies: waiting time no relationship with

mortality, EXCEPT for fulminant liver failure

• need for objective medical criteria score

PELD score

Pediatric end-stage liver disease score

• Albumin

• Total bilirubin

• INR

• Growth failure

• age (<1y)

• PELD = 4.80[Ln serum bilirubin (mg/dL)] + 18.57[Ln INR] - 6.87[Ln albumin (g/dL)] + 4.36(<1 year old) + 6.67(growth failure)

PELD score

• Additional PED points for specific risk factors:

hepatopulmonary syndrome, metabolic diseases,

liver tumors

• Unfortunately : PELD score is not a successful

predictor of post-transplant outcome

SKILLS

The transplant operation

• Until early 80ies : whole liver transplantation of

donor with weight close to the recipient’s weight

• 50 % mortality due to waiting for the ideal donor

• Development of new techniques changed this

high mortality to a current overall survival rate of

> 90%

Technical developments

1. Split liver (80ies)

2. Living related liver transplantation : segment 2-

3 in pediatric LTX

Donor surgery in LDLT

• Standardized technique of segmentectomy

S2&3

• Ethical concern :

• mortality : 1/1000 LD

• Morbidity : 10%

• Strict selection criteria

Anatomy of the liver

Recipient surgery

1. Hepatectomy

2. Anhepatic phase

3. Implantation:

1. piggyback anastomosis of the VCI

2. End-to-end running anastomosis of the PV ( portoplasty )

3. End-to-end interrupted anastomosis of the HA

4. Biliairy anastomosis : hepaticojejunostomy

4. 2 abdominal drains

5. Abdominal patch if GRBWR >4M

Check perop patency

with

Duplex-doppler

Recipient surgery

Hepatic Dupplex doppler Per- and postoperative hepatic duplex doppler will help in detecting :

- Venous kinking/thrombosis

- Arterial flow problems (RI) : tardus-parvus wave pattern

- Biliairy stricture

Normal = - PV : continuous flow pattern towards the liver w/ mild

velocity variations due to respiration

- IVC & hepatic veins: phasic flow pattern

- Arterial : rapidly systolic upstroke with continuous diastolic flow

- Bile ducts should not be visible

PASSION

Nothing great in the world has ever

been accomplished without

passion

Georg Wilhelm Friedrich Hegel

Passion

• Every patient is different, every transplantation is

as starting from scratch

• Teamwork supplies everyone’s fuel

• “Fight” for every patient and their course, with or

without complications

Early postoperative course

- Primary non-function (rare)

- Vascular complications:

- HAT : 5-18%,

- PVT: 5-10%

- Biliairy complications : 24%

- lateral vs terminal leaks

- Biliary strictures

- calculi

Possible technical complications

Early postoperative course

• Hyperacte rejection :

• Rare after PLtX

• Minutes to days post PLTX

• Mediated by ABO or preformed anti-HLA AB

• Intravascular thrombosis, intestinal haemorraghe

• Acute rejection : • 20-50 % during first week post PLTX

• T ceel dependent

• May be cell-mediated, antibody-mediated or both

• No imaging modality sensitive or specific to diagnose rejection

• Symptoms : fever, lethargy, anorexia, increased liver enzymes

• Usually reversible with steroids (sliding scale)

Bacterial/viral infections

Rejection

Late complications

• Most common cause of long-term alograft loss

• Occurs over months/years

• Incidence : 5-10%

• Risk factors :

- previous episode(s) of acute rejection

- poor HLA match

- long warm ischaemia time

- CMV infection

- raised blood lipids

- inadequate immunosuppression

• 2 subtypes: - vanishing bile duct syndrome R/ change IS or re-TX if non-responsive

- progressive ischemic injury of the bile duct re Tx

Chronic rejection

Post transplant

malignancies

• 4-5% of LDLT recipients will develop a malignant

tumor

• 4-fold increased risk for lymphoma ( non-Hodgkin

lymphoma) compared to normal population

Drugs

The following drugs must be permanently available in the center :

• Immunosuppressive drugs (Medrol, Solumedrol, Prograf,

Neoral, Cellcept, Rapamune, Zenapax or Simulect)

• Drugs used to treat acute rejection episodes such as

methylprednisolone

• Wisconsin University solution

• Drugs to treat bacterial, viral, and fungal or parasitic infections.

AIM FOR EXCELLENCE

“ Nothing we had done in advance would

have prepared us for the enormity of the task Thomas Starzl, the puzzle people

3D bioprinting technology

Outcome after PLTX • European liver transplantation Registry (1988-2005):

• UNOS :

• SPLIT : 1y patient survival 88%

1y alograft survival 82%

4y patient survival 83%

4y alograft survival 74%

< 2Y old > 2y old

1y patient survival 81% 84%

1y alograft survival 71% 73%

10y patient survival 74% 75%

10 alograft survival 60% 61%

Outcome after PLTX

• Role of age :

• Survival for infants <1y or <10kg : 65% and 80%--> improved due to technical innovations, better graft preparations

• Role of diagnosis :

• Similar survival rate if metabolic or cholestatic liver disease

• Early survival in acute liver failure and liver tumor group is worse, Long-term survival is similar to those of oter recipients

• PELD score of >20 or deterioration of PELD score before PLTX

Outcome after PLTX

• Graft-related outcome:

• Inferior when donor age : < 6mo or >60y

• Graft type (whole, reduced, split, LD) : less clear

• In experienced centres : no difference

• In lower volume centres : older patients with LDLT : less favourable outcome

• Severity of patient’s illness @ Tx : most important prognostic factor : PELD>20, severe growth retardation, acute liver failure : significant lower overall survival

• Long-term survival : influenced by consequences of prolonged IS like infection, PTLD, renal inufficiency, hypertension, DM, coronary artery disease.

Future perspectives

• Hepatocyte stem cell transplantation

• Genetic therapy

• Bio Artificial liver systems

Conclusion

• Success of liver transplantation is directly related to the strength of the team

• As a surgeon, not only technical skills, but also a broad knowledge of immunosuppression, pathology and psychological insight are of critical value in the holistic approach of the child with ESLD

• A transplant patient is a patient for life, but being allowed a +/- normal life throughout

THANK YOU