Progress in pediatric liver transplantation—The Birmingham experience

Progress in Pediatric Liver TransplantationThe Birmingham Experience By D. Talbot,

O.A. Achilleos,

B.K. Gunson,

f? McKiernan, Birmingham,

l This report describes the evolution of the Birmingham, UK experience with pediatric liver transplantation from 1983 to present. Two hundred liver grafts were placed in 168 children less than 17 years of age. The current survival rate exceeds 80%. Copyright o 1997 by W.B. Saunders Company INDEX

WORDS:

Hepatic

failure,

liver

transplantation.

L

IVER TRANSPLANTATION is well established as a treatment option in pediatric liver failure. This procedure is performed in a restricted number of centers because highly specialized multidisciplinary services are required. Pediatric transplant programs started some time after the procedure had been established in adults in the early to mid 1980s. The operations, at first, replicated the standard adult operation using a whole liver graft. Results have been improved by developing specialist pediatric support. This was achieved by a combination of aggressive medical and nutritional supportQ to lessen or reverse the deterioration before liver transplantation.3-6 It became evident that children would die while awaiting a liver allograft simply because of the rarity of size-matched donors. This led to the second surgical development, which was to use larger donors and reduce their livers to size by using selected segments and discarding the remainder.6-10 The third surgical development was to divide one liver into two (split livers).“-l4 Finally livingrelated donor programs were developed by certain centers with their attendent risks to the donor (usually left lateral segment from parent to child).15-l7 These procedures have allowed the donor pool to be expanded further, hence enabling the mortality rate for those on the waiting list to be kept as low as possible. Since 1983 the unit has transplanted over 200 livers into pediatric recipients, and we present a review of the development of this program. MATERIALS

AND

From the Liver and Hepatobiliary Unit, Queen Elizabeth Hospital and the Children’s Hospital, Birmingham, England. Address reprint requests to Liver and Hepatobiliary Unit, Freeman Hospital, High Heaton, Newcastle Upon Tyne. England. Copyright o 1997 by WE. Saunders Company

710

D.A. Kelly, J.A.C. Buckels,

and A.D. Mayer

years of age) underwent transplantation with 200 liver grafts between 1983 and 1995 (median follow-up, 4 years). The transplants were performed for irreversible liver failure (acute, 48 and chronic, 152), congenital metabolic abnormalities, and tumors (Table I). The definition of the difference between acute and chronic. in adult terms, is a liver failure patient who is unlikely to survive 48 hours without a liver graft. For children this definition is generally more loosely interpreted and covers children who are experiencing increasing reversible episodes of liver decompensation. The transplants were performed either at the Queen Elizabeth (elective cases) or at the Birmingham Children’s Hospital (acute cases). In 1989 a dedicated pediatric hepatologist was appointed, and this service has now been expanded to three such consultants. In addition, nutritionists. psychologists, and social workers have joined the team to allow a multidisciplinary approach in the assessment and management of the children and their famihes. The surgical input is from the adult transplant surgeons. Since 1990 a combined approach has been adopted with mainly two surgeons, one performing the liver reduction and the other performing the recipient operation. The changing surgical techniques over time are illustrated in Table 2. Full-sized grafts were transplanted by the standard orthotopic technique. The majority of reduced liver grafts were left lateral segments implanting the donor left hepatic vein onto the recipient inferior vena cava, which was left intact (Brisbane technique). In most cases it was possible to perfuse the graft with a standard arterial anastomosis between the bifurcation of the hepatic artery and the gastroduodenal artery. Occasionally when recipients required regrafts or when an arterial vessel was encountered that was too small, an arterial conduit was required, which was anastomosed directly to the aorta. The portal vein was anastomosed to the native vein often at the bifurcation with the coronal vein (left gastric vein). With a thrombosed native portal vein a “jump” graft was sometimes required, anastomosing the donor portal vein via a vein graft to the superior mesenteric vein. The biliary drainage was established by a series of techniques including a gallbladder conduit, which was used in the early grafts and subsequently duct-to-duct or duct-to-Roux en Y small bowel loop.‘* Children undergoing transplantation at the Queen Elizabeth Hospital were transferred back to the children’s hospital after a period of stabilization in the adult intensive care unit.

METHODS

The records of the patients who had recetved liver transplants at either the Queen Elizabeth Hospital or Children’s Hospital. Birmingham were reviewed. One hundred sixty-eight children (less than 17

OOZZ-3468/97/3205-0012$03.00/0

S. Beath, England

RESULTS

The outcome after pediatric liver transplantation is summarized in Table 3 and the survival rate shown in Fig 1. Not surprisingly the worst results were at the beginning of the program when the mortality rate was 100%. The main causes of failure other than technical difficulties at the beginning of the program were primary nonfunction and hepatic artery thrombosis. With improved quality of donor organs because of better intensive care support of the donor and improved perfusion fluids (University of Journal

off’ediatric

Surgery,

Vol32,

No 5 (May),

1997: pp 710-713

LIVER TRANSPLANTATION

711

Table 1. The Changing

n

Medran Median

recipient recipient

Etiology Acute

of liver

age (yr) weight (kg)

Recipient

1985

Features

1986

With

1987

the Developing

Program

1983

1984

1

1

4

5

5

1988

1989

1990

1991

1992

1993

12

23

27

31

30

30

12 32

14 42

13 39

6 17

2 15

31

1.5 11

3.2 13

3.9 15

2.5 13

1.7 13

1.8 10

0

0

0

0

2

3

6

10

11

5

5

6

1 0

1 0

4 0

5 1

3 1

9 8

17 12

17 6

20 12

25 12

25 13

25 10

0.9 8

199415

disease

Chronrc Bilrary atresia Metabolrc

0

0

1

3

1

0

1

7

7

6

6

7

Viral Malignancy

0 1

0 0

0 0

0 0

2 0

1 0

2 0

3 0

5 1

2 1

2 1

4 0

Other

0

1

3

1

1

3

8

11

6

9

8

10

Table 2. The Changing

Median donor Whole graft Reduced

age (yrl

graft

Splrt graft

Donor

Features

and Operative

Techniques

With

the Developing

Program

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

199415

46 1

8 1

11.5 4

7 5

7 3

4 4

5 13

11.5 12

14 7

10 11

11 12

12 7

0

0

0

0

2

8

10

15

24

18

16

22

0

0

0

0

0

0

0

0

0

1

2

2

1991

1992

1993

199415

Table 3. Outcome

for the Recipients

0

0

0

0

0

0

2

2

2

0

0

0

Vascularthrombosis (% acute regraft/yr)

0 0

0 0

0 0

0 0

0 0

1 9

3 28

3 23

3 19

1 3

1 3

0 0

0 1

0 1

0 0

0 4

0 2

0 5

1 10

3 2

1 7

1 4

3 3

2 7

0

0

100

20

40

50

47

91

73

86

90

of totaliyr)

Wisconsin solution) the incidence of primary nonfunction is now very low, and we have had none since 199 1. Another factor that is known to contribute to primary nonfunction is cold ischemic time. In a review of the European Transplant Registry, the incidence of graft primary nonfunction was found to rise steadily with cold ischemia from 14 hours upwards.lg It is interesting to note that with the advent of liver reduction, which increased the cold ischemic time, the incidence of primary nonfunction increased in 1989 through 1991. This is documented in Table 4 where the complications with the different techniques are listed. It is evident here that in 1990 the primary nonfunction in the reduced group accounted for 26.6% of transplants as opposed to 0% for the wholeliver grafts. At this time the reduction and implant was performed sequentially but since the introduction of the two-consultant system the procedures are performed simultaneously so that the cold ischemic time has been reduced. The vascular complication rate was appreciable in the late 1980s and highest in 1990 (Table 4). Liver reductions were expected to minimize the incidence of vascular complications because the caliber of the graft vessels used for the anastomosis were larger. However in 1990 33.3% of liver reductions had a vascular complication

1987

1988

in Birmingham

Aucte regrafl Primary nonfunction

(% survival

1986

Transplantation

1984

Late regraft Death
1985

of Liver

1983

1989

1990

77.4

(hepatic artery or portal vein thrombosis) as opposed to 16.6% for whole grafts. Since 1991 the incidence of vascular complications has declined to five cases out of 91 transplants (4.4%). This is probably attributable to a combination of the learning curve and also to the dual surgeon system allowing each to be reasonably “fresh” in contrast to the “exhausted” old days. In only one case was an arterial conduit required, and this was for a split liver graft. Table 5 illustrates the changing biliary complication rate with time. The complications include biliary strictures requiring intervention together with biliary leak from the anstomosis. Initially a gallbladder conduit was used with a relatively high incidence of problems (mainly cholethiasis and strictures)18 masked here by the high mortality rate for other reasons. It is interesting to note that the complication rate remained the same despite the reducing ages of the recipients. In addition, after the learning curve of the liver reduction surgery was over: the incidence of biliary complications was marginally less in the reduced grafts as opposed to the whole grafts (the donor bile duct was larger). The results were better in the duct-to-Roux en Y anastomosis as opposed to duct-to-duct anastomosis (19.3% versus 15.6%).

712

TALBOT

Table 4. Vascular

100

With

Whole

80

,+PERCENTAGEi

Fig 1.

Pediatric

recipient

survival

over time.

The nature of both donors and recipients has also changed since the program began. The age of the donor has generally increased (Table 2). Early donors were generally older because the transplants were full-sized liver grafts (first donor, 46 years), but their age declined rapidly to a median of 4 years in 1988. With the introduction of liver reduction and splits, the age of the donor has increased to a maximum of 50 years (median, 14). When possible children and young adults are used as donors to ensure a good-quality graft to minimize the chances of primary nonfunction and arteriosclerosis producing arterial insufhciency and thereby producing biliary complications. Also, the donor-to-recipient weight ratio has to be restricted despite the reduction, to ideally 6 to 1, and at the most, 10 to 1. A larger donor would create problems for vascular anastomoses and recipient wound closure. The recipients have also changed. In the earlier days only chronic liver disease patients could be considered because they were stable enough to await the sizematched donor. Since the beginning of the reduced liver program the more unstable acute liver failure children could undergo transplantation with their attendent highrisk status. This was most evident in 1990 when 37% of patients underwent transplantation for acute failure with a total survival rate of 9 1%.

Complications Whole

For many years liver transplantation was considered an experimental procedure performed only as a last resort. It is now, in adult terms, an established treatment option, though success in pediatric patients has been slower to evolve. Birmingham and Kings College Hospital perform

in Early Regraft

Grafts

With

or Death

lime

1987

1988

1989

1990

1991

1992

1993

graft

199415

3

4

13

12

7

11

12

7

Vascularcomplication

0

1

6

2

1

0

1

0

Nonfunctron

0

0

0

0

1

0

0

0

Reduced graft Vascularcomplication

2

8

10

15

24

18

16

22

0

2

2

5

5

1

2

0

Nonfunctron

0

1

3

4

1

0

0

0

1

2

2

1

0

0

0

Split

-

-

-

-

-

Vascularcomplicatron Nonfunction

-

-

-

-

-

-

the vast majority of pediatric liver transplants within the United Kingdom. The survival results after transplantation show a dramatic improvement only from 1990. Before this, though they offered some hope to parents of severely ill children, the results were generally disappointing. The improvement in results has been because of a combination of the development of a specialist pediatric program and the designation of two consultant surgeons who perform the donor and recipient operations in combination. The expansion in numbers of pediatric transplants performed was caused by the development of the liver reduction program. This has been most evident for children in fulminant failure where invariably there would be no pediatric donor available. With the continuing attrition of children dying while on the waiting list there is now pressure to develop the program further. This will occur by the development of the split program, one donor organ into two recipients. This brings further difficulties to the program as well as doubling the work load on the intensive care of the children after surgery. The surgical, anesthetic, and theater staff have to work sequentially producing obvious exhaustion, which could compromise the success of the second graft. This difficulty could be addressed by sharing these organs between centers with active

Table

5. Biliary Complications (%) Against Time Periods With Varying Surgical Technique 1983. 1986

n

DISCUSSION

Resulting

and Reduced

ET AL

11

Gallbladder condurt/duct Gallbladder condurtiroux Duct/duct 1%) Duct/roux (%) Brliary complicatrons in Whole graft (%) Reduced

graft

t%)

(%) (%)

6 (0)

1987. 1990

67

4 (25)

2 (50) 2 (0)

0 (01 1 (0)

20 (51 43 (12)

1991. 199415

122 0 (0) 0 (0)

31 (19) 91 (14)

Ill 1 (9)

3132 (9)

7/37 (19)

o/o (0)

3135 (9)

13/85 (15)

LIVER TRANSPLANTATION

713

pediatric programs as already occurs in Belgium and Holland. ACKNOWLEDGMENT The authors acknowledge the success of this program and the assistance in preparing this manuscript to the pediatricians D. Kelly, P.

McKiernan, and S. Beath; the surgeons P. McMaster, A D. Mayer, and J.A.C. Buckels: the anesthetists I. Freeman. M Sealey, J. Ltlley. and S. Huggins: the theater staff R. Horne, C Pritchard. V Powles. A. Fisher. L. Edmund% M. O’Meara. and C. Rawlmgs; Intensive care staff m adult and pediatric units; paediatrrc nurses, radiologists. nutrniomsts. social workers. psychologists. and physiotherapists

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