Institute of Liver & Biliary Sciences

Dedicated to Excellence in Patient Care,

Teaching & Research in Liver & Biliary Diseases

Pusa Road, New Delhi (India)

www.blkhospital.com

Director

HPB Surgery & Liver Transplantation

BLK Super Speciality Hospital

drsanjaynegi@gmail.com

Current Concepts in Liver Transplantation

Sanjay Singh Negi

Centre for Digestive & Liver Diseases

Multifaceted organ: Powerhouse & Factory

Large functional reserve: Remarkable capacity to recover from injury, S/S if >80% of liver damaged, Can remove upto 75% though restrict upto 35%

Unique features of liver

Normal liver after resection or donation: Functional recovery in 1-2 weeks Regenerates anatomically to 100% of size in 4-6 weeks

Regenerative capability

Capacity to recover lost in diseases & liver fails Unlike renal failure where hemodialysis, in Liver failure: No clinically effective liver

dialysis, Stem cell transplant experimental Medical treatment is supportive, LTx is the only curative option

Curative Treatment for Liver Failure

Develops slowly (≥ 6 mths) due to continuing slow damage to the liver Causes: Viral (HBV, HCV), Alcohol abuse, Steato-hepatitis

S/S: Jaundice, Ascites, Encephalopathy, GI Bleed, Mucosal Bleed or Effects on other organs (HRS, HPS)

Chronic Liver Disease

CLD: Survival in absence of LTx

1 2 3

Encephalopathy None 1-2 3-4

Ascites Absent slight Mod.

Albumin (mg/dl) > 3.5 2.8-3.5 < 2.8

PT (seconds prolonged) <4 4-6 >6

Bilirubin (mg/dl) <2 2-3 >3

Grades A: 5-6 B: 7-9 C: 10-15

Child Turcotte Pugh (CTP) Score

Survival according to CTP Score

Points Class 1-year survival 2-year survival

5-6 A 100% 85%

7-9 B 81% 57%

10-15 C 45% 35%

0.957 X Log e (Sr. Creatinine mg/dl)

+ 0.378 X Log e (Sr. Bilirubin mg/dl)

+ 1.120 X Log e (INR)

+ 0.643

MELD Score

3-mth mortality according to MELD Score

MELD < 9 10 -19 20 - 29 30 - 39 > 40

Mortality 1.9 % 6 % 19.6 % 52.6 % 71.3 %

Mortality+

too sick 2.9 % 7.7 % 23.5 % 60.2 % 79.3%

R. Wiesner et al; Gastroenterology 2003; 124: 91-96

Develops suddenly (days to weeks) due to massive damage to otherwise normal liver Cause: Viral (HAV, HEV), Drugs (AKT, PCM)

S/S: Jaundice, Encephalopathy, Coagulopathy, MODS Rapid progression leading to death. Timely LTx is the only cure.

Acute or Fulminant Liver Failure

ALF: Etiology

INDIA USA UK France

Viral (%) 95 60 30 50-60

Major cause HEV/HBV Cryptogenic Non A - Non B HBV/HAV

Drugs 4.5 30-35 60 15-20

Major drugs INH/RCIN PCM PCM NSAID/PCM

Others 0.5 5 10 10-15

LTx: Best treatment with consistent outcome

Wide spectrum & Rapid pathological progression

Properly selected patients in a timely fashion

Acute or Fulminant Liver Failure

Model Components Etiology Sensitivity Specificity Validation

KCH (O’Grady 1989)

Paracetamol Arterial pH <7.3 OR Any 3 within 24 hrs HE Grade 3 or 4 INR >6.5 Sr. Creat >2.26 mg%

Non-Paracetamol

INR>6.5 (PT>100) OR Any 3 Age <10 or >40 Etio (Seroneg, Drug) JEI >7 days INR >3.5 (PT>50) Sr. Bil >17.5 mg%

All

Acetaminophen

Non-Acetaminophen

69% 92% Yes

Clichy (Bernuau 1986)

HE Grade 3 or 4 V<20% in <30 yr V<30% in >30 yr

Hepatitis B

86%

76% Scarce

AIIMS (Acharya 1996)

Any 3 Age >40 PT prolongation >25 sec Sr. Bil>15 CE

HEV/HBV

Drugs

86% 90% No

PGIMER (Dhiman 2007)

Any 3 Age >50 PT prolongation >35 sec JEI >7 days CE HE Gr 3 or 4 Sr Creat >1.5

Viral Hepatitis

91% 65% No

Multi-Variable Prognostic Models (Mathematical)

Clinical judgment

Balancing Act

Balance

Balance

Death in absence of LTx Death even after LTx

Recovery only with LTx Risks of LTx & IS

Too early Too late

Liver Resection or Liver Transplantation?

Liver Cancer (HCC)

Lesser resources & Greater applicability No graft (no waiting / donor risk)

Lesser morbidity / mortality No risk of IS

Liver Resection for HCC

Curative modality of choice in Non-Cirrhotics & Compensated Cirrhotics Bridge to LTx & May allow selection of patients for LTx

Liver Resection for HCC

Anatomical resections with maximal parenchymal preservation

Liver Resection for HCC

IOUS Guided Hepatectomy

Safe, lower morbidity & ascitis especially in cirrhotics No compromise in margins & long-term outcome

Experienced surgeon, Single lesion < 5 cm, Peripheral segment

Laparoscopic Approach

Widest possible margin

Treats ‘Field Change’ (Lesser recurrence)

Treats underlying CLD (No PHF)

Liver Cancer (HCC): LTx

HCC Criterion

Criterion Component

Milan Single tumor ≤5 cm

Upto 3 tumor each ≤3cm

UCSF Single tumor ≤6.5 cm

Upto 3 tumor each ≤4.5cm

Total tumor diameter ≤8cm

Toronto No number or size restriction

No systemic symptoms

Not poorly differentiated (if beyond Milan)

Each criterion assumes no extra-hepatic disease & no macrovascular invasion

Acute or Fulminant Liver Failure Survival <90% in absence of LTx (CTP ≥7, MELD>15)

Complication (PHT bleed, Recc. Enceph, SBP, HRS, HPS) Liver cancer: HCC

Serious QoL issues (Repeated Hosp./Tt, Itching, Fatigue)

When to refer CLD patient for LTx?

Biliary atresia Wilsons disease

Genetic Disorders Causing liver damage: Crigler-Najjar Syndrome or PFIC

No liver damage but cured after LTx: Primary Hyperoxaluria, Familial Amyloid Polyneuropathy, Maple Syrup Urine Disease etc.

Pediatric: Indications for LTx

Contra-indications for LTx

Severe cardiopulmonary disease

Active infection/uncontrolled sepsis

Extrahepatic malignancy (criteria for cure not met)

Active alcohol/substance abuse

Lack of psychosocial support / non-compliance

•Brain Dead, Heart Beating •Extended Criterion

•Split

Living Donor

Supply: Source of organs

Deceased Donor

•Related •Unrelated

Declaration of Brain (Neurological) Death

Irreversible coma

Absence of spontaneous movement

No response to noxious stimuli

Irreversible loss of brainstem activity and

respiratory centre function or Demonstration of

cessation of intracranial blood flow

Deceased Donor Living Donor

Source of organs: Merits & Demerits

•Better quantity (Whole graft) •Donor complication or coercion N/A •Lower recipient complication

•Better graft quality •Minimal waiting time •Elective surgery

Supply: Lack of Deceased Donation

Lack of awareness

Socio cultural factors

Lack of organized effort to promote and coordinate

organ donation

Scarcity of ICU beds and donor m/m facilities

At BLK: Robust system for Organ donation, Highest rate in Delhi-NCR, 30% of LTx

Deceased Donation: Further Hurdles

Timely availability of a deceased donor organ before

the patient becomes too sick for LTx

Logistics of organ harvesting and transport

Likelihood of marginal grafts due to paucity of

expertise in management of brain dead donors

Difficulty for the recipient to arrive at the transplant

centre at short notice

Demand-Supply Mismatch

Liver disease 3.5 million patients CLD 4 million patients

20,000 patients/yr need LTx 2000 children/yr need LTx

Demand: Magnitude of problem

LDLT: Relevance to Indian Scenario

Lack of cadaveric organs

Closely knit families: willing for donation

What is the Outcome after LTx?

Outcome following LTx

Underlying etiology

Nature of graft

Severity of pre-transplant illness

MELD

Complications (PHT, SBP, HRS, HPS)

ALF

When to refer patient for LTx: Timing

INIE

RV

EN

TIO

N

Spontaneous recovery without LTx

Spontaneous unlikely, Recovery with LTx

Succumb despite LTx

Too early Too late

SICKEST SICKER SICK

Highly skilled & dedicated human resources

Infrastructure 24 x 7

Pre-requires for LTx programme

Dedicated Twin UCV OTs

Isolated ICU Cubicles with Independent AHUs

Close healthy family member ABO compatible, Age 18 to 50

No co- morbidities, No malignancy, Normal LFT, No fatty liver Suitable surgical anatomy Willing to accept the risk

LDLT: Who can donate?

Donor Work-up

Minimal amount of liver tissue that can safely be removed from a donor

While providing an adequate amount of liver for the recipient

Essence of LDLT is to strike a balance between:

Recipient Hepatectomy

Graft Implantation

Waveform: Low resistance, Brisk systolic uptake PSV >30 cm/sec RI: 0.5-0.8

LTx is best treatment with consistent outcome (CLD, ALF, HCC)

LDLT has similar or better outcome than DDLT

Early identification & Timely referral

Outcome: severity of illness & nature of graft

LDLT: Ethical & Donor safety concerns

Critical to ensure adequate graft volume & quality

Take Home Message

Teamwork

drsanjaynegi@gmail.com