1. Liver Transplantation – ‘who needs a liver transplant’
Nalaka Gunawansa
Vascular and Transplant surgeon
Annual academic sessions
College of Surgeons – Sri Lanka

2. Indications For LT Acute (fulminant) hepatic failure
Early graft failure (PGNF, HAT)
Late graft failure (CR, biliary cirrhosis, HAT, recurrent disease)
Chronic Liver disease (HBV, HCV, AIH, ALD, NAFLD)
CPS> Severe bone disease (esp PBC/PSC)
Uncontrolled variceal bleeding Hepatopulmonary syndrome
Diuretic resistant ascites Portopulmonary hypertension
Chronic hepatic encephalopathy Hepatorenal syndrome
SBP Severe malnutrition Intractable pruritis
Metabolic liver disease (alpha 1 AT def, Wilsons etc.)
HCC
Paediatric – biliary atresia

3. Fulminant liver failure - acute HBV, HAV, drugs, infection etc

4. Hepatocellular carcinoma
Llovet et al. Hepatocellular carcinoma. Lancet 2003

5. Worldwide Incidence of Hepatocellular Carcinoma
HCC Epidemiology
Worldwide Incidence of Hepatocellular Carcinoma
Slide 5
Worldwide Incidence of Hepatocellular Carcinoma
The incidence of HCC varies considerably around the world with the highest rates in Southeast Asia and sub-Saharan Africa (areas where HBV infection is endemic and high). The United States have recently moved into the intermediate incidence areas (age-adjusted incidence rates close to 4 per 100,000 person-years).
El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology Nov;127(5 Suppl 1):S27-34.
High (> 30:100,000)
El-Serag HB,
Gastroenterology
2004
Intermediate (3-30:100,000)
Low or data unavailable (< 3:100,000)

6. Management options Surgical resection Liver transplantation
Ablative therapy (ethanol, RFA, cryo)
Chemoembolization
Systemic chemotherapy

7. Barcelona Clinic Liver Cancer Staging Classification (BCLC)
Liver transplantation (CLT/LDLT)
PEI/RFA
New agents
Curative treatments 50%-75% at 5 years
Randomized controlled trials 40%-50% at 3 years vs 10% at 3 years
Chemoembolism
Single
Increased
Associated diseases
Normal No
Yes
Terminal stage (D)
Symptomatic
treatment
Stage A-C
PST 0-2, Child-Pugh A-B
Multinodular, PST 0
Portal invasion, N1, M1
Portal pressure / bilirubin
3 nodules <3 cm
Intermediate stage (B)
PST >2, Child-Pugh C
Stage D
Very early stage (0)
Single <2 cm
Carcinoma in situ
Early stage (A)
Single or 3 nodules
<3 cm, PST 0
Advanced stage (C)
Portal invasion,
N1, M1, PST 1–2
PST 0, Child-Pugh A
Stage 0
Resection
CLT/LDLT = cadaveric liver transplantation/living donor liver transplantation; PST = Performance Status Test.
Slide 190
Barcelona Clinic Liver Cancer Staging Classification (BCLC)
This shows the Barcelona Staging classification for HCC which was recommended by the AASLD guidelines, and has been the only classification that has been externally validated.
Llovet JM et al. Lancet. 2003; 362:1907

8. HCC; Liver Transplantation
Non-cirrhotics with multiple HCC
Cirrhotics - simultaneous treatment of HCC and underlying cirrhosis
No macrovascular invasion
No extra-hepatic spread
Strict selection criteria on size
Milan criteria – HCC <5cm or up to 3 nodules, largest < 3cm each
UCSF criteria – HCC <6.5cm, total diameter <8cm
5yr survival – 70%
5yr recurrence rate – 15% *
* Mazzafero, et al, NEJM 1996

9. Survival After Transplant for HCC: UNOS Experience
HCC Treatment
Survival After Transplant for HCC: UNOS Experience
1.0 .8 .6
Cumulative
Survival .4 .2
P<0.001
Slide 214
Survival After Transplant for HCC: UNOS Experience
There has been a steady improvement in survival of patients receiving liver transplantation for hepatocellular carcinoma in the United States. This is primarily due to use of the Milan criteria for patient selection, as well as to technical improvements in liver transplantation.
J Clin Oncol Dec 1;21(23): Epub 2003 Oct 27. Comment in: J Clin Oncol Dec 1;21(23): The outcome of liver transplantation in patients with hepatocellular carcinoma in the United States between 1988 and 2001: 5-year survival has improved significantly with time. Yoo HY, Patt CH, Geschwind JF, Thuluvath PJ.
Days
365
730
0195
1460
1825
Patients at Risk
Yoo HY, et al, J Clin Oncol 2003

10. Resection vs Transplantation for HCC: Intention-to-Treat Analysis
HCC Treatment
Resection vs Transplantation for HCC: Intention-to-Treat Analysis
By “Intention-to-Treat analysis”, survival is comparable between OLT and Resection
77 surgical resections, 87 transplants
Resection
Transplantation
I yr survival
85%
84%
3 yr
62%
69%
5yr
51%
Slide 218
Resection vs Transplantation for HCC: Intention-to-Treat Analysis
Based on “Intent-to-Treat” analysis the survival (1 and 3 year) for hepatic resection for HCC is comparably similar to liver transplantation if the waiting time is short and the drop out while on the waiting list was low.
Llovet JM, et al, Hepatology 1999

11. Resection versus Transplantation
HCC + cirrhosis Treatment
Resection versus Transplantation
TRANSPLANTATION
curative in early stage
advanced cirrhosis – Childs Pugh B, C
Low recurrence rates
Shortage of organs
drop-out while awaiting transplantation
Immunosuppression
RESECTION
readily available
Childs Pugh A without significant PHT
No need for lifelong immunosuppression
high rate of recurrence of HCC
Slide 219
Resection versus Transplantation
There are pros and cons to both hepatic resection and liver transplantation.

12. Resection vs. Transplant for HCC Three Year Recurrence Rates
HCC Treatment
Resection vs. Transplant for HCC Three Year Recurrence Rates
Author / Year Number Recurrence
Resection Transplant Resection Transplant
Iwatsuki % 42.9%
Michel % 14.3%
Vargas % 0%
Tan % 20%
Otto % 36.0%
Llovet % 2.3%
Weimann % 0%
Figueras % 0%
DeCarlis % 9% %
0 - 43%
Slide 220
Resection vs. Transplant for HCC Three Year Recurrence Rates
It demonstrates that 3 year recurrence rates for HCC after liver resection are higher compared to those who underwent liver transplantation. The high recurrence rates observed with liver transplantation were from earlier series when candidates were not carefully selected based on tumor bulk.
Overall
Wong LL, Amer J Surgery 2002

13. Outcomes of HCC Treatment: Observational Population-based study1
0.8
0.6
(Kaplan Meier Estimate)
Survival
Transplant
Resection
0.4
Ablation
Slide 257
Outcomes of HCC Treatment: Observational Population-based study
The cumulative 5-year survival in 2,963 patients with HCC diagnosed between 1992 and 1999 and identified in SEER-Medicare datasets. Patients were grouped into 4 groups depending on the type of therapy received. Median overall survival was 104 days following HCC diagnosis with the longest survival in the transplant group (852 days) and the shortest survival in the group with no treatment (58 days). In the survival analysis, transplantation led to the longest survival, followed by resection. Neither ablation nor TACE yielded prolonged survival (3 year survival was less than 10%).
El-Serag HB, Siegel AB, Davila JA, Shaib YH, Cayton-Woody M, McBride R, McGlynn KA. Treatment and outcomes of treating of hepatocellular carcinoma among Medicare recipients in the United States: a population-based study. J Hepatol Jan;44(1):
TACE
0.2
0.5 1
1.5 2
2.5 3
3.5 4
4.5 5
Follow up Duration (Years)
El-Serag HB, et al, J Hepatology 2006

14. CADAVERIC ORGAN DONOR SHORTAGE
Waiting List Registrants
Donors
UNOS July 2001 3

15. Living Donor: Liver Transplantation
Driven by:
Expansion in number of patients requiring liver transplantation
Shortage of deceased donor organs
- genuine lack of donors
- cultural beliefs (eg Japan)
Increase in waiting list deaths
- Fulminant liver failure
- Disease progression

16. Living Donor Transplantation
Recipient Advantages
Elective surgery
Avoid long waiting time
Less ischaemia time for the graft
‘Healthy’ liver
Problems of maintaining brain dead donor
Recipient Disadvantages
Increased technical complications
Arterial stenosis / thrombosis
Biliary leak / stricture (x3 commoner)
Small for size

17. Living Donor Transplantation:
Donor Disadvantages
Psychological stress to donor and family
Inconvenience / risk of evaluation process
Operative mortality ( 1/300)
(1/1000 for L/lobe, 1/200 for R/lobe)
- 15 reported deaths worldwide (12 R/lobe, 3 L/lobe)
Major postoperative complications (10-20%)

19. Donor criteria
No psychological or social contraindication to live donation.
Age 21 – 55
Graft to recipient weight ratio > 0.8%
BMI < 30
No history of cardiovascular disease
No history of significant respiratory disease.
No diabetes, kidney dis, etc…….
No history of excess alcohol, liver disease
Suitable liver anatomy
Donor safety is paramount – no exceptions to the rule

24. Liver Transplantation in SL – the future
Live donor LT
Split liver
Extended criteria donors
Donation after cardiac death
A co-ordinated approach to organ donation, procurement, sharing and transplantation