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ate Mortality in 679 Consecutive Liver Transplant Recipients: Theothenburg Liver Transplant Experience

.J. Lukes, G. Herlenius, M. Rizell, L. Mjörnstedt, L. Bäcman, M. Olausson, and S. Friman

ABSTRACT

Purpose. Liver transplantation (OLT) is an established treatment with excellent earlyoutcome. However, the long-term results are hampered by side effects of immunosuppres-sion, cardiovascular morbidity, recurrent disease, and chronic rejection. We analyzedcauses of late death (�2 years post-OLT) in 679 consecutive primary recipients in ourinstitution.Materials and methods. A total of 679 primary OLT recipients including thoseretransplanted within 3 months between January 1985 and August 2005 were identified;460 (67.7%) patients survived �2 years. The indications were cholestatic disease (35.1%),postviral (11.4%), alcoholic (12.9%), fulminant hepatic failure (7.0%), cryptogenic (3.1%),autoimmune hepatitis (4.8%), malignancy (7.7%), and others (18.0%). Sixty three patients(9.3%) died �2 years post-OLT. For 51 patients, sufficient records were present toestablish the cause of death.Results. Four hundred sixty (67.7%) patients survived �2 years. Their median age was58 years with, 43.7% older than 60 and 11.1% older than 70 years. Sixty three patients(9.3%) died at a median time of 69 � 4.8 months post–primary OLT; 49.1% died ofmalignancy and 13.7% of vascular complications and infectious complications respectively.Conclusions. Late mortality in our material is mainly due to malignant disease.Compared to other published reports on late mortality, the proportion of malignancy,especially recurrent, as cause of late death is higher. This might reflect a more generousapproach toward accepting older patients and a higher proportion of patients with various

malignant diseases accepted for OLT.

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IVER TRANSPLANTATION (OLT) is an establishedtreatment with excellent early outcomes. Significant

rogress has been made during the last decades, making it aoutine procedure. However, the long-term results are ham-ered by the side effects of immunosuppression, cardiovascu-

ar morbidity, recurrent disease, de novo and recurrentalignancy as well as chronic rejection. In the Scandina-

ian countries certain indications for OLT are moreommon than in the rest of the transplanting world, namely,he cholestatic diseases of primary biliary cirrhosis andrimary sclerosing cholangitis, which were 11% and 18%,espectively. There are only a few reports in the literaturen late mortality in OLT with varying outcomes dependingartly on factors like age distribution, underlying diagnosis,nd demographical data.1–9 No reports are available on acandinavian cohort. In this study we therefore analyzed

he causes of late death (�2 years post-OLT) among 679 4

2006 by Elsevier Inc. All rights reserved.60 Park Avenue South, New York, NY 10010-1710

ransplantation Proceedings, 38, 2671–2672 (2006)

onsecutive primary OLT recipients transplanted at ournstitution.

ATERIALS AND METHODS

total of 679 primary OLT recipients, including those retrans-lanted within 3 months between January 1985 and August 2005,ere identified for this retrospective analysis; 460 (67.7%) patients

urvived �2 years. The indications for OLT were cholestaticisease (35.1%), postviral (11.4%), alcoholic (12.9%), fulminantepatic failure (7.0%), cryptogenic (3.1%), autoimmune hepatitis4.8%), malignancy (10.0%), and others (15.7%). Sixty three

From the Department of Surgery and Transplantation, Sahlg-enska University Hospital, Göteborg, Sweden.

Address reprint requests to Daniel J. Lukes, MD, PhD, Depart-ent of Surgery and Transplantation and the Wallenberg Labora-

ory for Cardiovascular Research, Sahlgrenska University Hospital,

13 45 Göteborg, Sweden. E-mail: daniel.lukes@vgregion.se

0041-1345/06/$–see front matterdoi:10.1016/j.transproceed.2006.07.029

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2672 LUKES, HERLENIUS, RIZELL ET AL

atients (9.3%) died �2 years post-OLT. For 51 patients, sufficientecords were present to establish the cause of death. The data werextracted from the European Liver Transplant registry, Nordiciver Transplant Registry (part of Scandia Transplant, Århus,enmark) as well as hospital paper and computer records.All numerical data are expressed as percentages.

ESULTS

our hundred sixty (67.7%) patients survived �2 years.heir median age was 58 years with, 43.7% older than 60nd 11.1% older than 70 years. Sixty three patients (9.3%)ied at a median time of 69 � 4.8 months post–primaryLT; 49.1% died of malignancy, either recurrence (21.6%)

r de novo malignancy (23.5%), and 13.7% of vascular andnfectious complications respectively. The causes of deathre listed in Table 1.

ISCUSSION

ate mortality in our material was mainly due to malignantisease. Compared to other reports on late mortality, theroportion of malignancy, especially recurrent, as cause of

ate death is higher herein.8,10–12 The reason for this is notbvious, but might reflect a more generous approach to-ard accepting older patients and a higher proportion ofatients with various malignant diseases accepted for OLT.uring the first 10 years (1985 to 1995) the percentage

ndergoing OLT because of malignant disease was 13.6%;uring the last 10 years (1995 to 2005) the percentage wasown to 9.0%. Also a shift was seen toward other cancerorms, during the first era 88% were hepatocellular carci-oma; during the second, 32%. During this time theecipients also became older. The mean age at the time ofLT was 46.5 � 1.5 years versus 49.4 � 2.3 in the second

ra. Perhaps more important is a higher proportion of olderecipients, since during the first decade almost no recipientsere above the age of 60 years when transplanted. It haslearly been demonstrated that with increasing recipients

Table 1. Causes of Late (>2 Years Post-OLT) Mortality inPrimary Liver Transplant Recipients

Mortality Category Number of Deaths

otential complications of immunosuppression 21 (41.2%)De novo malignancy 12 (23.5%)Infection 7 (13.7%)Renal failure 1 (2.0%)Respiratory failure 1 (2.0%)

ascular complications 7 (13.7%)Cardiovascular 6 (11.8%)Cerebrovascular 1 (2%)

ecurrent disease 15 (29.4%)Malignant 11 (21.6%)Non-malignant 4 (7.8%)astrointestinal bleeding 2 (4%)uicide 1 (2%)nknown 4 (7.8%)

ge, there is an increased likelihood of de novo tumors.9 2

The other two major causes of late death were vascularnd infectious complications (13.7% each), which were notore common than reported by others in combined adult

nd pediatric materials.6,9,11,13 Infectious problems wereainly seen in younger (here below 60 years of age) and

ediatric recipients, whereas cardiovascular mortality in-reased with age.8,10,12 Both of these complications are toome extent influenced by the degree of immunosuppres-ion, though the European levels generally were lower thanhe North American ones.

In summary, the number of late malignancies in our mate-ial was higher than that reported by other. This might reflect,specially early on, a more generous approach toward accept-ng patients with malignant disease but also a relatively highroportion of elderly recipients. These data have to be seen

n the light of liver transplant accessibility, which has beennd still is relatively good in the Scandinavian countries.

CKNOWLEDGMENTS

jörn Brandsäter, MD, PhD, Department of Gastroenter-logy, Rikshospitalet, Oslo, Norway and Helena Tarnow,N and Ulla Haljamäe, RN, both Department of Surgery

nd Transplantation, Sahlgrenska University Hospital,öteborg, Sweden, are gratefully acknowledged for excel-

ent assistance with access to registry data.

EFERENCES

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