- Liver transplantation (LTx) is the only curative treatment option for end-stage liver disease and acute or chronic liver failure. It provides consistent outcomes with proper patient selection and timely transplantation. - Living donor liver transplantation (LDLT) is especially relevant for the Indian scenario due to the lack of deceased donors. It allows for shorter wait times but requires ensuring donor safety and adequate graft volume/quality. - Referral for LTx should be timely based on disease severity and prognostic scores to prevent patients from becoming too sick or dying without transplantation. Outcomes depend on factors like etiology, graft quality, and pre-transplant illness severity.

1. 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

2. 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

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

4. 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

5. 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

6. CLD: Survival in absence of LTx

7. 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

8. 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%

9. 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

10. 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

11. 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

12. 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

13. LTx: Best treatment with consistent outcome
Wide spectrum & Rapid pathological progression
Properly selected patients in a timely fashion
Acute or Fulminant Liver Failure

14. 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)

15. Clinical judgment
Balancing Act

16. Balance
Balance
Death in absence of LTx Death even after LTx
Recovery only with LTx Risks of LTx & IS
Too early Too late

17. Liver Resection or Liver Transplantation?
Liver Cancer (HCC)

18. Lesser resources & Greater applicability
No graft (no waiting / donor risk)
Lesser morbidity / mortality
No risk of IS
Liver Resection for HCC

19. Curative modality of choice in Non-Cirrhotics & Compensated Cirrhotics
Bridge to LTx & May allow selection of patients for LTx
Liver Resection for HCC

20. Anatomical resections with maximal parenchymal preservation
Liver Resection for HCC

21. IOUS Guided Hepatectomy

22. Safe, lower morbidity & ascitis especially in cirrhotics
No compromise in margins & long-term outcome
Experienced surgeon, Single lesion < 5 cm, Peripheral segment
Laparoscopic Approach

23. Widest possible margin
Treats ‘Field Change’ (Lesser recurrence)
Treats underlying CLD (No PHF)
Liver Cancer (HCC): LTx

24. 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

25. 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?

26. 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

27. 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

28. •Brain Dead, Heart Beating
•Extended Criterion
•Split
Living Donor
Supply: Source of organs
Deceased Donor
•Related
•Unrelated

29. 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

30. 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

31. 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

32. 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

33. Demand-Supply Mismatch

34. 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

35. LDLT: Relevance to Indian Scenario
Lack of cadaveric organs
Closely knit families: willing for donation

36. What is the Outcome after LTx?

37. Outcome following LTx
 Underlying etiology
 Nature of graft
 Severity of pre-transplant illness
 MELD
 Complications (PHT, SBP, HRS, HPS)
 ALF

38. When to refer patient for LTx:
Timing
INIERVENTION
Spontaneous recovery
without LTx
Spontaneous unlikely,
Recovery with LTx
Succumb despite LTx
Too early Too late
SICKESTSICKERSICK

39.  Highly skilled & dedicated human resources
 Infrastructure 24 x 7
Pre-requires for LTx programme

40. Dedicated Twin UCV OTs

41. Isolated ICU Cubicles with Independent AHUs

42. 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?

43. Donor Work-up

44. 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:

45. Recipient Hepatectomy

46. Graft Implantation

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

48.  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

49. Teamwork
drsanjaynegi@gmail.com