Expanding Selection Criteria

for Living Liver Donor

Shin Hwang

Division of HBP Surgery and Liver Transplantation,

Department of Surgery, University of Ulsan College of
Medicine and Asan Medical Center, Seoul, Korea
 Living Donor Liver Transplantation

• Shortage of deceased donor organ donation

• Donor safety is always most important.

• Selection of living donors and extent of donor

hepatectomy

• Innovative concepts and surgical techniques

to optimize liver sharing between living donor
and recipient
 First 1000 liver transplantations at AMC
181+a
(1992, 11, 20 - 2004, 11, 10)

160 152
140 DDLT 137
123
120 LDLT
105
100
Cases

SLT: 5 82
80
Reduced: 1
60

40 33 30
25 20
20 16 16
4 6 63 811 10 11
4
3 2
0
1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 12+a

2004
 First 1000 LDLTs at AMC
1000
Adult
n = 892
800

Cumulative case umber

600

400
r e b mu esacl a unn A

200
Pediatric
n = 108
0

Year
 Living donor liver grafts at Asan Medical Center
2:1
RL+LL
2:1
LL +LL 870
LL+S1
384
NUMBER

Modified
RL 261

Extended
156 RPS
Adult RL
(6th RL graft)
LL RL
74
Pediatric
41

LLS2
1994 1997 1997 1998 1999 1999 2000 2000 2001 2004
Dec Feb Jul Mar Jan Sep Mar Nov Apr Nov
World-first 1000 LDLTs at a single-center
Kyoto University

Tanaka et al. Living donor liver transplantation in Japan and Kyoto University: what can we learn?
J Hepatol 2005;42:25.
 Recipient Outcome in 1000 LDLTs at AMC

Pediatric

Adult
oi t r opor pl avi vr u S

Posttransplant months
 Vancouver Form

On the care of Liver Organ Donor

on September 15 and 16, 2005

Live liver donation should only be

performed if the risk to the donor is justified
by the expectation of an acceptable
outcome in the recipient.

Transplantation 2006;81
 Vancouver Form
Donor Evaluation
 Initial screening of potential donors (Age < 60)
 Complete history and physical examination
 BMI > 30 kg/m2 may increase risk of surgical complications
 Lab testing (compatible ABO blood type)
 No psychosocial, ethical issue, or concerns about the motivations of
the donor.
No active or uncontrolled psychiatric disorder.
 Imaging studies (Donor remnant volume, GRWR)
For donor Safety:
Calculated remnant liver > 30% of the original
liver volume with complete venous drainage
For recipient Safety:
Estimated GRWR > 0.8%
 Possible or routine preoperative liver biopsy: steatosis < 20% for right
liver donation
 Estimated Worldwide Living Liver Donor Mortality
Hepatic failure
- Excessive resection
- Lipodystrophy
- NASH
- Remnant liver torsion
Sepsis
MOF

Massive bleeding

Pulmonary embolism
Anesthesia-related
For right liver donors, mortality rate is up to 0.5%.
Aspiration pneumonia
For left liver donors, the mortality rate is 0.1%.
Peptic ulcer-related
Transplantation 2006;81
Living donor mortality reports
 Living donor complications

Vancouver forum
 Living donor complications

RL donation is associated with an increased

morbidity (range 20-60%, overall 35%) and more
severe complications than LL or LLS donation.

RL donation is associated with an increased morbidity (range 20-60%,

overall 35%) and more severe complications than LL or LLS donation.
Lo et al. Complications and Long-Term Outcome of Living Liver Donors: A survey of 1,508 cases in Five Asian Centers. Transplantation 2003;75:
S12.
 General
Donor safety operative risk

Learning
curve

Hepatic resection rate Hepatic steatosis

Anatomical variations
 Operation Risk and Extent of Hepatectomy

Donor Risk

Extent of Donor Hepatectomy LLS LL RL ERL

Chronology Pediatric Adult

LDLT LDLT
 Operation Risk and Graft Types

Graft type n Morbidity (%)

S3 monosegment 8 0
Lateral segment 753 8.2
Posterior segment 13 15.4
Left lobe 484 12.0
Left Lobe + S1 140 15.7
Right lobe 443 19.0
1841 12.4%
meshita K et al. Operative morbidity of living liver donors in Japan. Lancet 2003; 362:687-6
Permissible Extent of Donor Hepatectomy
Remnant liver volume

35% or 30%
of total liver volume
Permissible Extent of Donor Hepatectomy

Small original liver e.g. 1.6 of GRWR or 85% of SLV

35% or 30%
of total liver volume

-> 0.5 > GRWR

30% > SLV
Posthepatectomy liver function and regeneration

• Age
- General operative risk
- Regeneration power
• Fatty change
- Loss of functional liver mass
- Detrimental effect
• Deprivation of MHV outflow
: Congestion-induced ischemic injury
 Donor Hepatectomy
up to 70% of total liver volume

• 20-40 years
• No or minimal fatty change
• No venous congestion (MHV preservation)
 Donor Hepatectomy
up to 65% of total liver volume

• 20-40 years
• No or minimal fatty change
• No venous congestion (MHV preservation)
 Is CT volumetry reliable
to assess the remnant liver proportion?

Not always YES.

Pitfall of CT volumetry
Interlobar volume proportions:
Arterial phase vs Venous phase
Discrepancy among CT volumetry, interlobar color demarcation
and real transection planes
 Right lobe graft: CT volume vs Weight

n = 359 - RL CT volume
1
4
0
0

: 779 ± 133 mL
1
2
0
0

- Actual RL graft weight

R

1
0
0
0
: 692 ± 107 g
R_Vo_
lt
CT volume

8
0
0
(10% difference)
6
0
0
Correlation Coefficient
(r) = 0.838/ r2 =0.702
4
0
0

4
0
0 5
0
0 6
0
0 7
0
0 8
0
0 9
0
0 1
0
0
0 1
1
0
0
Actual graft weight =
A
ct
u
a
l
Actual Graft Weight 163+0.678*CT volume
 Left lobe graft: CT volume vs Weight
8
0
0
n = 113 - LL CT volume
7
0
0 : 372 ± 92 mL

- Actual LL graft weight

6
0
0
o_Lt

: 384 ± 82 g
Vl
CT volume
R

5
0
0
_

4
0
0 (Little difference)
3
0
0

Correlation Coefficient
2
0
0 = 0.841 / r2 =0.707
2
0
0 3
0
0 4
0
0 5
0
0 6
0
0

Actual Graft
A
c
t
ul Weight
a Actual graft weight =
107+0.745*CT volume
 Right / Left lobe grafts: CT volume vs Weight

Over-estimation
40.00 Right Lobe
- Graft
Error Ratio (%)

20
.00

Ⅹ Left Lobe
- Graft
0.0
0

Error Ratio (%) =

(E-A)/A*100 E E:
estimated volume
-20.00
(mL)
A: actual weight
Under-estimation (g).
2
00 4
00 600 8
00 1
000 12
00

Actual Graft Weight

 Current guidelines of permissible donor conditions
for graft type selection only focused on donor safety
-------------------------------------------------------------------------------------------------------------------------
-------
Right lobe graft
- Donor age of 20 - 30 years and no fatty change
-> Remnant left liver volume >= 30% of original liver volume
- Donor age of 30-50 years or mild fatty change up to 30%
-> Remnant left liver volume >= 35% of original liver volume
Extended right lobe graft
- Donor age of 20 - 30 years and no fatty change
-> Congestion-free remnant left liver volume† >= 30% of original liver
volume
- Donor age of 30-50 years or mild fatty change up to 30%
-> Congestion-free remnant left liver volume† >= 35% of original liver
volume
Right posterior segment graft
- Donor age of 20-60 years and fatty change up to 50%
-> Separate branching of right posterior portal vein
and right posterior segment volume
larger than left lobe plus caudate lobe volume by 100 mL
Left lobe with or without caudate lobe
- Donor age of 20-60 years and fatty change up to 50%
-> Congestion-free remnant right lobe volume >= 30% of original liver volume
Left lateral segment
- Donor age of 20 - 60 years and fatty change up to 50%
-------------------------------------------------------------------------------------------------------------------------
 Type of Grafts in 1218 Adult LDLT at AMC
( from Feb 1997 to Dec 2006 )
Donor Donor
200 Remnant Remnant
180
Liver ≥ 35 Liver > 30 %
LL Dual 170
160 RL LL+S1
%
167

140 MRL PS
120 ERL E-LLS 113

100
80
80 75
59
60 51 54
45
40 38 34 35
22 28 26 27
14
20 10 15 13
98 12 8 8 9
5
14
6
333 62 7 55 3 1 7 3
2 11 1 3 21
1
0
1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
 How to share MHV

1 2 3 4 5

6 7 8 9 10

11 12 13 14 15

16 17 18 19 20
 HVC mapping using CT

Interlobar
Interlobar margin
margin in
in arterial
arterial phase
phase Mapping of predicted HVC
CT
CT

W2 H2
H2
H2 H1
H1
W2
W2 W1
W1
W1 H1

HVC width in venous phase & volume study Ventral end of GB bed
5-mm
5-mm thickness
thickness CT
CT scan
scan
Proportional Amount of HVC to Right Lobe Volume

V5
V8
19% of RLV
15% 25% 35%
31%

25% 35% 45%

54% of RLV

35% 45% 55%

3-D Reconstruction of Liver Anatomy

2 types of imaging software

Semi-automatic Image-processing

Hepavision2, Germany VoxelPlus, Korea,

Factors associated with MHV reconstruction

Graft size
to recipient

Amount
of HVC Availability of
Vessel graft

Reconstruction
technique
Hepatic venous congestion after MHV procurement
Fates of S4 after procurement of RL+MHV

Uneventful regeneration Atrophy

Anatomical Variations of MHV
Right lobe graft with or without MHV trunk
depending on V4 anatomy
4 Main types and 12 Subtypes of V4s
(2-D view from head to feet)

A1 A2 A3
A
MHV-dominant

B1 B2 B3
B
MHV-dominant,
enabling tailoring
C1 C2 C3
C
LHV-MHV Mixed
IVC
D1 D2 D3
D
LHV-dominant umbilical portion
 Proportional and Configurational Differences

AMC, n=328, 2004 Nakamura, n=83, 1981

A1 A2 A3
A
43.3%

B1 B2 B3 9.5%
B
12.2%
type III

C1 C2 C3 28.6%
C
28%
type II

D1 D2 D3
D 61.9%
type I
16.5%
Direct matching is not reasonable due to different configurations.
 Five types of Right Lobe Grafts

• Simple RL
• Modified RL (MHV reconstruction)
• Modified extended RL
• Extended RL with V4b preservation
• Extended RL (with complete MHV trunk)
Anatomy of ventral branching of MHV

A B C
Customized transection to obtain single V5

A B C
Congestion at the remnant left liver

5%
of left liver volume
Modified extended right lobe graft

ERL + MRL

Hwang et al. Hepatogastroenterology 2006

Modified right lobe graft
Cryopreserved vein graft

V8

V5
Conversion from type A to type C

A B C
 Tailored MHV transection
with V4b preservation in type B

V4b
RL graft with MHV trunk
+ V4b preservation
RL graft with MHV trunk
Interposition reconstruction
True extended RL graft
Selection of Right Lateral Sector graft

600 gm- weighed RLS graft

Right lateral sector graft: How difficult?

AMC

Limitation in anatomy (+)

Tokyo

Limitation in anatomy (-)

Really to most transplant surgeons ?
AMC Indication for RPS Procurement
Knacks and pitfalls in left liver grafts

1 2 3 4 5

6 7 8 9 10

11 12 13 14 15

16 17 18 19 20
Massive Hepatic Venous Congestion
V8-Preserving Left Lobe Graft Procurement
 MHV-LHV venoplasty

A B
CT follow-up of V8 preservation

Preoperation

Postoperation: arterial phase venous phase

Were they actually benefited from V8 preservation?
• Collateral formation
• CT attenuation changes
Pre-enhancement
Pre-enhancement

Preoperation Low-density portion

Arterial
Arterial phase
phase Venous
Venous phase
phase

Hypoattenuation and hyperattenuation

Pre-existing large MHV-RHV communication
1-week CT

2 out of 27
Hyperattenuation predominance

Arterial
Arterial phase
phase Venous
Venous phase
phase 1-week CT

Well-compensated congestion
: 12 /27 (44%)
 Hypoattenuation predominance

Arterial
Arterial phase
phase Venous
Venous phase
phase 1-week CT

Poorly-compensated congestion
: 8 / 27 (30%)
after exclusion with 3 anatomical conditions
 Selection of Left lobe plus S1 graft

10% increase of graft weight

Hwang et al. Simplified standardized technique for living donor liver transplantation using left liver graft plus caudate
lobe. Liver Transpl 2004;10:1398-1405.
Left lobe plus caudate graft
Living donor left lateral segmentectomy
Left lobectomy without MHV
Persistent bile leak requiring remnant S4 resection

Preop 1-week

2-month 4-month
Removal of the non-functioning ischemic parenchyma
 First Dual Graft LDLT and Outcome

5 days

400 gm

300 gm
2 mos
 AMC 2000-2005
Left lobe Left Lateral segment Lateral segment
lobe

Left lobe Lateral segment

82 53 (1; Cadaveric graft) 10

Posterior Posterior
Left lobe segment Lateral segment segment

Left
Right lobe lobe

27 (5; Lateral segment) 2 3

Various kinds of 177 dual living donor liver transplantation among 993 adult
living donor liver transplantation.
 Indication of Dual LDLT

In Donor
Donor Volume ratio
Macro-steatosis
Remnant Liver R:L > 2:1
> 30%
≤ 30% steatosis > 30%

In Recipient

GRWR < 0.8 %

 Adult LDLT at AMC

GRWR or SLV/GV according to Graft Type

Mean Minimum Maximum

GRWR RL 1.04 0.62 1.67

LL 0.89 0.49 1.13
Dual 1.03 0.85 1.26

SLV/GV RL 55.6 36.6 82.7

LL 43.1 26.5 52.9
Dual 52.3 42.9 73.4
Safety of Dual-Graft Donors
Donor Risk

Immoderate Right Lobe harvest

Two Left Lobes harvest

 Hepatic Steatosis in LDLT

Steatosis Deceased-donor LT Living-donor LT

Mild yes many controversy

(< 30%) between 20% and 30%

Moderate yes or no usually no

(30% ≤ < 60% )

Severe absolutely no absolutely no

( ≥ 60%)
 Liver Biopsy
BMI is not always reliable.

No biopsy-related complication in consecutive 1600 donors

Macro- vs. Microvesicular steatosis

More effective
on weight reduction
Macro Micro
Macro- and Microvesicular steatosis

Simple steatosis: Macro =< Micro

Pathologic : >> (e.g., NASH)
Slow weight reduction by 5% over 3 mos
is recommended.
 Gilbert Syndrome donor
Dual Living-Donor Liver Transplant by using Gilbert Disease Donors

Right-sidedGraft
Right-sided Graft Left-sided
Left-sidedGraft
Graft
Leftlobe
Left lobe:: 250
250gmgm Left
Leftlobe
lobe:: 320
320gmgm
((<<35
35%%ofofTLV)
TLV) ((<< 35%
35%of
ofTLV
TLV))
Fattychange
Fatty change::10%
10% Fatty
Fattychange
change::40%
40%

UNOS2a
UNOS 2a(Male,
(Male,56)
56), ,MELD
MELDscore
score40 40
HBV-Cirrhosis,Hepato-Renal
HBV-Cirrhosis, Hepato-RenalSyndrome
Syndrome
TB 47.8
TB 47.8mg/dl
mg/dl BUN/Cr
BUN/Cr169169/ /11.5
11.5mg/dl
mg/dl PT13.4
PT 13.4%
%

Posttransplant 7th day Posttransplant 11th mo

 Unrelated Donors

Good Samaritan donors

- 34 /1600 (2.1%) at AMC

- 29 out of 34 were contributed as one of dual-graft donors

- Left lobe graft was preferred due to Donor Safety.

 Donor exchange LDLT
ABO-Incompatible adult LDLT: Is it justifiable?

Five sets at AMC

PBC (F/54) HBV-LC (F/54)

O+ AB+
Recipient 157cm/47kg 150cm/52kg
MELD 16 MELD 11

nephew(M/32) unrelated(M/49)
Donor A+ O+
Left Lobe Left Lobe + S1
Steatosis 10% Steatosis 25%
450 gm 360 gm
GRWR 0.9 GRWR 0.8
Donor exchange LDLT using Good Samaritan donor

Recipient A B

Donor A B C
No donor Good
Samaritan
 No Anatomical Limitation
in living liver donor ?

Technical feasibility &

Complication rate
Availability of
living donor
 Left-sided gallbladder

- 1999, Kyoto U (Transplantation, 1999;68:1160)

: 4 / 379
-> 1 turn down; 3 Left Lobes to 2 pediatric & 1 adult

- 2004 AMC (Liver Transpl 2004;10;141)

: 3 / 642
-> 1 Right Lobe, 1 RPS, 1 Left Lobe
Left-sided GB as live RL donor

upper margin of
Right duct
Cystic duct
the duodenum

Round ligament
Umbilical vein
P4
P2,3
Real right portal vein
 Posttransplantation 1 year

Remnant left lobe Right lobe graft

Donor Recipient
2 Right Hepatic Arteries

2%
 Complex anomalous hepatic veins
: usually overcome by innovative surgical techniques
 Case

Hepatic venous congestion

after complex HV reconstruction
Donor liver with complex hepatic vein anatomy

• Accessory RHV-dominant RHV anatomy

• Convergence of V8 at MHV root
• Venous congestion from incomplete reconstruction
• Wall stent insertion
Donor Liver Anatomy
Donor Liver Anatomy

Video
Donor Liver Anatomy
Posttransplant Day 1

Video
Wall stent insertion at day 1
Posttransplant Day 2

Video
Posttransplant Day 7

Video
Successful revascularization of complex SHVs

Vein anatomy-based customized

reconstruction method should be used
instead of conventional methods.
Complex anomalous hepatic veins
Quilt venoplasty
 Normal variations of the Portal vein
Nearly always acceptable

I II III

n = 157 (79.7%) n = 15 (7.6%) n = 25 (12.7%)

Rare anomalous branching of the portal vein
: Too high operative risk for technical challenge

A
UP

Type IV
Preoperative MR cholangiography
Multiple anomalous branching of the bile duct
: Acceptable with multiple anastomoses

A A
A

P P
Acc P
Acc P
P

3 bile buct anastomoses 4 bile buct anastomoses

Rare anomalous branching of the bile duct
: Too high operative risk for technical challenge

B4
Rare anomalous branching of the bile duct
: Pay special attention!

B2
Donor bile duct stricture
After 1 month
Denuding-induced bile duct stricture
ERBD
After 4 mos
Use of hepatitis B core Ab-positive allograft

40-45% of Korean liver donors: anti-HBc (+)

Risk of de novo hepatitis

HBV naïve Anti-HBc (+),

recipient anti-HBs (+)
recipient
Up to 70% Variably occurred
French data
Serum anti-HBc and HBV DNA in liver donors

1/22 11/21
(4.5%) (52%) Gut 2005;50:95
French data
Natural course of viral reaction
in HBV-naïve recipients without HBV prophylaxis

Gut 2005;50:95
French data
Natural course of viral reaction
in HBV-naïve recipient with low-dose HBIG < 50 IU/L

Gut 2005;50:95
Korean data
Anti-HBc (+) allograft to anti-HBs (+) recipient

Risk of de novo hepatitis is not always low.

3 pediatric recipients without HBV prophylaxis

1 HBV-naïve -> HBsAg sero-conversion after 14 mos

2 anti-HBs (+) -> HBsAg (+) after 16 and 20 mos

Transpl proc 2004;36:2311

Anti-HBc (+) allograft to HBs Ag (-) recipient

Prevention of de novo hepatitis

 HBIG monotherapy
- Low-dose method was preferred.
:100-200 IU/Kg or 5000 IU; anti-HBs titer > 100-200 IU/L
- High-dose method
:100-200 IU/Kg or 10,000 IU; anti-HBs titer > 500 IU/L
 Lamivudine

Anti-HBc-positive allograft requires HBV prophylaxis

regardless of recipient’s viral marker status.
 Perioperative Living donor management

Gabexate mexilate infusion since midnight

: Its effect is not proven on our prospective study yet.

Hyperalimentation after right lobe donation

Intraportal glucose-potassium-insulin infusion

for 1 week in high-risk donors

 Postoperative follow-up

1 week: Liver CT, HB scintigraphy

1 mo: Liver CT or USG, lab tests

 3 mos: Liver CT or USG, lab tests

 12 mos: Liver CT or USG, lab tests

 Operative scar care

Hypertrophic scar occurred in 10-20%.

For young female donors

Meticulous follow-up by a plastic surgeon

(who was also a donor for his father)
 Living Donor Liver Transplantation
1-year study at AMC (Apr 2005 – Apr 2006)

Total No. of patients performed

living donor evaluation (385)

Number of patients rejected Number of patients rejected

for recipient problems (69) for donor problems (86)

Total number of patients who

underwent LDLT (230)

385 patients -> 230 LDLT (59.7%)

 Donor-related problems rejected for LDLT
Reasons Number of
potential donor
ABO incompatible 6
Significant medical diseases 5
Small remnant volume in Donor 39
Severe fatty change 14
Small graft size 4
Anatomical variation 2
Viral marker abnormality 6
Abnormal LFT 1
Refusal to donate 11

total 86 of 385 (22%)

From 2005 April To 2006 April at the Asan Medical Center

 Asan Medical Center, Seoul, Korea

1 case of really serious complication

(CRF after contrast-induced ARF)
in 1600 living liver donors to date
 Conclusions
• In the situation of deceased donor organ
shortage, living donor liver transplantation can
be a feasible option.

• Donor safety would be guaranteed only after

strict observation of donor selection criteria
and meticulous surgery.

• Innovative surgical techniques may contribute

to overcome anatomical variations of the
donor liver without imperilment of donor
safety.