R

B

RcTwppeterr

P

A5app1cf2c

0d

1

etransplantation of the Liver

.I. Gustafsson, L. Backman, S. Friman, G. Herlenius, P. Lindnér, L. Mjornstedt, and M. Olausson

ABSTRACT

Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction.The outcome of a second procedure depends upon several factors, some of which are notdefined at the time of the decision to retransplant. This study is an analysis of all re-TX of theliver performed at our unit between January 1995 and January 2004. Among the 474 liver TXwere 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication forre-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation,peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graftsurvivals. Patients who underwent re-TX did not differ from those transplanted once withregard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliarytract complications/chronic rejection, one-third hepatic artery thrombosis, and one-thirdothers, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/Chepatitis. The re-TX were “urgent” in 29 and “elective” in 26 cases. Complications werecommon; about half of the patients were reoperated due to bleeding or biliary problems. Todate (May 2004), 15 patients have died (12 “urgent” and 3 “elective”), of whom 5 had wellfunctioning grafts. In summary, liver re-TX is a complicated procedure associated withsignificant mortality and morbidity, but considering that the actual patient group has a poor

prognosis without re-TX, the results are nevertheless encouraging.

hmt

bswbciw

wttroc

o

tU

ETRANSPLANTATION (re-TX) is the only thera-peutic option for irreversible liver graft failure and

onstitutes 8% to 17% of procedures in several studies.1–5

he clinical outcome depends on several factors, some ofhich are not defined at the time of decision to retrans-lant, including graft quality, cold ischemia time, anderioperative factors. Furthermore, because re-TX is gen-rally associated with inferior survival rates and higher costshan the first TX, careful analysis of the potential benefits isssential to justify its role in an era of organ shortage andising costs.2,5 In the present study, we reviewed all livere-TX performed in our unit during the last 9 years.

ATIENTS AND METHODS

mong 474 liver TX performed from January 1995 to January 20045 (11.6%) were re-TX in 47 patients (27 male and 16 femaledults, 18 to 67 years old and 4 children aged 1 to 5 years). Threeatients received a third, one a fourth, and one a fifth graft. Therimary diagnoses were primary sclerosing cholangitis (PSC) in0 patients (21%), hepatitis C cirrhosis in 7 (15%), alcoholicirrhosis in 5 (11%), chronic active hepatitis in 5 (11%), acute liverailure in 4 (8%), cryptogenic cirrhosis in 3 (6%), other hepatitis in

(4%), and primary biliary cirrhosis (PBC), secondary biliary

irrhosis, hepatitis B cirrhosis, hepatitis E cirrhosis, autoimmune g

041-1345/06/$–see front matteroi:10.1016/j.transproceed.2006.02.120

438

epatitis, familiar amyloidotic polyneuropathy, hereditary tyrosine-ia, Alagille syndrome, biliary atresia, hepatoblastoma and gas-

roschisis in 1 patient (2%) each.Liver TX were performed with hepatectomy and venovenous

ypass in most cases; the “piggy back” technique was used occa-ionally. Choledochojejunostomy is sutured to a Roux-en-Y loopas regularly chosen in PSC patients as well as when preferredefore split livers or re-re-TX since it can be used in otherircumstances at the surgeon’s discretion. One rapidly deteriorat-ng young patient received a right lobe from his father. Six patientsith renal impairment underwent a combined liver and kidney TX.Three patients with portal vein thrombosis were transplanted

ith cavoportal hemitransposition. In five cases, it was impossibleo close the abdomen owing to organ swelling. Three patients werereated openly, one succumbed in the ICU, and two subsequentlyeceived autologous skin grafts to cover the organs with excellentutcomes. In two patients, a Gore-Tex patch was temporarily used toover the defect. Mean operative time was 9.5 � 4.5 hours with a

From the Transplantation and Liver Surgery Unit, Departmentf Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.Address reprint requests to Dr B.I. Gustafsson, Transplanta-

ion and Liver Surgery Unit, Department of Surgery, Sahlgrenskaniversity Hospital, S-413 45 Göteborg, Sweden. E-mail: bengt.

ustafsson@surgery.gu.se

© 2006 by Elsevier Inc. All rights reserved.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 38, 1438–1439 (2006)

mMit

R

Ta1ptCmtftefwmo

tttc

t(hemsfc5tro

wT

D

LomdaTmc

sfwpad

rctgabcvfstrc

rw

R

s

t1

at

pT

r

aH

a6

m

FS

LIVER RETRANSPLANTATION 1439

ean CIT of 8.7 � 3.0 hours. Mean donor age was 45 � 14 years.edian peroperative blood transfusion was 6 (range, 1.2 to 80). The

mmunosuppression consisted of cyclosporine/azathioprine/steroids inhe first 2 years of the series and thereafter tacrolimus/steroids.

ESULTS

he indications for re-TX were hepatic artery thrombosis/rteritis in 15 and biliary complications/chronic rejection in5 cases (28% each), acute rejection in 6 (11%), andrimary graft nonfunction (PNF) in 4 (7%). There werehree portal vein thromboses (5%), one recurrence of hepatitis, and one de novo hepatitis B. Other indications wereultiorgan failure (MOF), bleeding, liver necrosis, caval stric-

ure, secondary biliary cirrhosis, and veno-occlusive disease. Inour cases, the diagnoses were unclear or a combination ofwo or three of the above. Twenty-nine re-TX were consid-red urgent and 26 elective. The time from TX to re-TX (orrom re-TX to re-re-TX) varied from 3 to 4380 days. Re-TXas performed within 3 weeks in 14 cases and up to 3onths in another 16. Nine additional re-TX were carried

ut within the first year and 16 after more than 2 years.There were two peroperative fatalities and two other pa-

ients did not survive the first postoperative day. Complica-ions were common; 21 patients (45%) were reoperated owingo bleeding or biliary problems. Severe sepsis occurred in a fewases and there was one early cytomegalovirus infection.

There were six acute rejections (11%). Median time inhe ICU was 5 days (range, 1 to 80) and on the ward 25 daysrange, 8 to 89). To date (May 2004), 15 patients (32%)ave died, 12 of whom were in the urgent and 3 in thelective group. The causes of death (12 of 15 within 3onths post-TX) were circulatory collapse in six patients,

epsis/MOF in four and caval thrombosis, myocardial in-arction, and cachexia (malignancy) in one each. In twoases, the cause of death is unknown. Three-month, 1- and-year actuarial survivals were 74%, 72% and 68%, respec-ively. Graft survival to date is 58%. Of the five patients whoeceived more than two liver grafts, three are alive. Four

ig 1. Patient survival after liver retransplantation in Göteborg,weden, 1995-2004.

ut of six kidneys transplanted are functioning; one patient T

ho received two kidney grafts died during his fifth liverX. Follow-up time ranged from 4 to 110 months (Fig 1).

ISCUSSION

iver re-TX is often a life-saving operation because it is thenly available therapy for irreversible graft failure. However,edical, ethical, and financial aspects concerning this proce-

ure are complex and somewhat controversial.2,5 This study isreview of all liver re-TX performed during a 9-year period.he present study population was chosen from 1995, since ourodern era began around this time with more consistent

linical strategies, surgical techniques, and general policies.The re-TX rate was comparable to those reported from

everal other centers, which probably reflects similar criteriaor the decision to retransplant.1–5 There was only one patientith PBC as the primary diagnosis, which reflects the good TXrognosis for this indication. Furthermore, PSC was associ-ted with some early complications related to the chole-ochojejunostomy.There seems to be little controversy as regards elective

e-TX: the survival rates reported in recent years areomparable to those following first TX. Our results supporthis conclusion with an 84% overall survival in the electiveroup. On the other hand, urgent re-TX was associated with57% survival. Based on large studies, survival models haveeen constructed where recipient age, bilirubin, creatinine,oagulation factors, need for intensive care/mechanicalentilation, and interval following primary tx seem to beactors predictive of outcome.2,5–8 An expected 1-yearurvival rate of less than 40% is considered a contraindica-ion for re-TX by some authors.6 We agree that urgente-TX should be considered with caution and on a case-by-ase basis.5,6 Living-related TX may be an option.5

In conclusion, we report favorable outcomes after livere-TX in elective cases. Careful clinical assessment and timing,hen possible, are essential in order to avoid urgent re-TX.

EFERENCES

1. Markmann JF, Markowitz JS, Yersiz H, et al: Long-termurvival after retransplantation of the liver. Ann Surg 226:408, 1997

2. Yoong KF, Gunson BK, Buckels JAC, et al: Repeat ortho-opic liver transplantation in the 1990s: is it justified? Transpl Int1(Suppl 1):S221, 19983. Kashyap R, Jain A, Reyes J, et al: Causes of retransplantation

fter primary liver transplantation in 4000 consecutive patients: 2o 19 years follow-up. Transplant Proc 33:1486, 2001

4. De Carlis L, Slim AO, Giacomoni A, et al: Liver Retrans-lantation: indications and results over a 15-year experience.ransplant Proc 33:1411, 20015. Azoulay D, Linhares MM, Huguet E, et al: Decision for

etransplantation of the liver. Ann Surg 236:713, 20026. Rosen HR, Prieto M, Casanovas-Taltavull T, et al: Validation

nd refinement of survival models for liver retransplantation.epatology 38:460, 20037. Wong T, Devlin J, Rolando N, et al: Clinical characteristics

ffecting the outcome of liver retransplantation. Transplantation4:878, 19978. Markmann J, Gornbein J, Markowitz JS, et al: A simpleodel to estimate survival after retransplantation of the liver.

ransplantation 67:422, 1999