Evolving Role of Liver Transplantation in Elderly Recipients · 2020. 1. 17. · 4Information Technology, Mayo Clinic, Jacksonville, FL The need for liver transplantation (LT) among

Original article | 1363

ORIGINAL ARTICLE

Evolving Role of Liver Transplantation in Elderly RecipientsOmar Y. Mousa,1 Justin H. Nguyen,3* Yaohua Ma,2 Bhupendra Rawal,2 Kaitlyn R. Musto,3 Marjorie K. Dougherty,3 Jefree A. Shalev,4 and Denise M. Harnois1,3*1 Divisions of Gastroenterology and Hepatology and 2 Biomedical Statistics and Informatics and Departments of 3Transplantation and 4 Information Technology, Mayo Clinic, Jacksonville, FL

The need for liver transplantation (LT) among older patients is increasing, but the role of LT in the elderly (≥70 years) is not well defined. We retrospectively reviewed all primary LTs from 1998 through 2016 at our center. Survival and associated risk factors were analyzed with Cox regression and Kaplan-Meier methods for LT recipients in 3 age groups: <60, 60-69, and ≥70 years. Among 2281 LT recipients, the median age was 56 years (range, 15-80 years), and 162 were aged ≥70 years. The estimated 5- and 10-year patient survival probabilities for elderly LT recipients were lower (70.8% and 43.6%) than for recipi-ents aged 60-69 years (77.2% and 64.6%) and <60 years (80.7% and 67.6%). Patient and graft survival rates associated with LT improved over time from the pre–Model for End-Stage Liver Disease era to Share 15, pre–Share 35, and Share 35 for the cohort overall (P < 0.001), but rates remained relatively stable in septuagenarians throughout the study periods (all P > 0.45). There was no incremental negative effect of age at LT among elderly patients aged 70-75 years (log-rank P = 0.32). Among elderly LT recipients, greater requirement for packed red blood cells and longer warm ischemia times were significantly associ-ated with decreased survival (P < 0.05). Survival of LT recipients, regardless of age, markedly surpassed that of patients who were denied LT, but it was persistently 20%-30% lower than the expected survival of the general US population (P < 0.001). With the aging of the population, select older patients with end-stage liver diseases can benefit from LT, which largely restores their expected life spans.

Liver Transplantation 25 1363‒1374 2019 AASLD.Received January 3, 2019; accepted June 15, 2019.

Liver transplantation (LT) among elderly persons, here defined as those aged ≥70 years, is controversial.(1,2) The world population is aging rapidly.(3) As longevity improves, the number of older patients being evaluated and considered for LT is increasing.(2,4) LT is a proven

lifesaving intervention for patients with acute and chronic end-stage liver diseases, extending life spans by an average of 15 years.(5) The role of LT among older patients is poorly defined, however, and it is even less understood for the elderly because the United Network for Organ Sharing (UNOS) caps recipient age at 65 years in estimation of risk adjustment.(1)

In 2017 in the United States, life expectancy at ages 60 and 70 years was 23.2 and 15.6 years, respectively.(6) In the context of saving lives, LT is considered a means of restoring patients’ expected life spans, as defined by the general population.(5,7,8) Few centers have reported results of LT for elderly recipients.(9,10) More data exist on LT among older recipients aged 60-69 years(11-17) and, in general, show that older patients have poorer survival outcomes than younger recipients. Several studies however—including 2 single-center expe-riences(9,10) and those using Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients national data(4,18,19)—show that increasingly more elderly patients are receiving LT and do relatively well compared with younger matched

MOusa et al.

Abbreviations: BMI, body mass index; CI, confidence interval; CIT, cold ischemia time; CMV, cytomegalovirus; CNS, central nervous system; DCD, donation after circulatory death; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; ICU, intensive care unit; LOS, length of stay; LT, liver transplantation; MELD, Model for End-Stage Liver Disease; PRBC, packed red blood cell; RR, relative risk; SD, standard deviation; UCLA ECD, University of California, Los Angeles, Extended Criteria Donor; UNOS, United Network for Organ Sharing; WIT, warm ischemia time.

Address reprint requests to Justin H. Nguyen, M.D., Department of Transplantation, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224. Telephone: +1-904-956-3261; E-mail: [email protected]

This study was partially supported by the National Institutes of Health grant R21 AG052822-01A1 to Justin H. Nguyen.

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mailto:[email protected]

MOusa et al. liver transplantatiOn, september 2019

1364 | Original article

patients; thus, LT should not be restricted on the basis of age alone.

Since the inception of our LT program, >5.0% of the LT recipients have been elderly.(20) In a previous study, we reported that 47 elderly LT recipients treated at our center between February 1998 and May 2004 fared as well as younger recipients, with equivalent 5-year sur-vival rates and posttransplant complications.(10) In the current study, we reviewed the outcomes of a larger cohort of elderly recipients of primary LT from a single center to further assess the role of LT among elderly patients.

Patients and MethodsThis study was reviewed and deemed exempt by the institutional review board. At our institution, clinical parameters for recipients and donors of LTs are pro-spectively recorded in an LT database. We retrospec-tively searched this database for the records of recipients of deceased donor LT at our transplant center from February 1998 through December 2016. We excluded cases that included cardiac procedures, pancreatodu-odenectomy, cholangiocarcinoma, combined heart or lung transplant, kidney transplant, pancreas transplant, kidney-pancreas transplant, prior LT, partial or split LT, and donation after circulatory death (DCD) transplants.

All patients underwent extensive, multidisciplinary, pre-LT evaluation and met the standard UNOS cri-teria for transplant approval by the LT selection com-mittee. Clinically available variables in the LT database were reviewed. For recipients, these included date of transplant, date of death, date of graft loss, and pri-mary diagnosis; general characteristics, including age and body mass index (BMI); physiologic Model for End-Stage Liver Disease (MELD) score; LT waiting

time; LT hospital length of stay (LOS); any required intensive care unit (ICU) admittance; previous abdom-inal surgery; status or condition at time of LT (eg, out-patient, in hospital, or in the ICU); cold ischemia time (CIT); warm ischemia time (WIT); intraoperative requirement of a packed red blood cell (PRBC) trans-fusion; and total operating time. For donors, these vari-ables included age; sex; BMI; donor risk index scores; University of California, Los Angeles, Extended Criteria Donor (UCLA ECD) scores; donor status of viral infections (hepatitis B virus [HBV], hepatitis C virus [HCV], and cytomegalovirus [CMV]); and cause of death.

Overall survival among LT recipients was compared with that of patients denied transplant and that of a matched cohort in the general US population. Survival data in the general US population were obtained from the National Vital Statistics reports in 2017.(6) Comparisons were performed among 3 LT recipient age groups: <60, 60-69, and ≥70 years (elderly). For each age group, the estimated expected lifetime m(x), where x is age in years of the patient at the time of LT, was estimated with linear regression (see estimation of expected life-times in the Supporting Materials); for age <60 years, m(x) = −0.9217x + 62.115 (R2 = 0.9996); for age 60-69 years, m(x) = −0.7673x + 23.92 (R2 = 0.9998); and for age 70-85 years, m(x) = −0.6056x + 15.923 (R2 = 0.9963). Estimated values were consistent with a previous report.(4)

statistical analYsisRecipient and donor pretransplant, operative, and posttransplant characteristics were compared among the same 3 age groups: <60, 60-69, and ≥70 years. Continuous variables were expressed as mean ± stan-dard deviation (SD), and categorical variables were expressed as n (%). Statistical significance was set at P ≤ 0.05 and was obtained using a χ2 test or t test. Univariate and multivariate Cox proportional hazards regression models were used to evaluate any associa-tion between overall survival or graft survival and the recipient’s demographics and pretransplant, opera-tive, and posttransplant characteristics. Relative risks (RRs) and 95% confidence intervals (CIs) were cal-culated. A recipient’s post-LT LOS was considered a time-dependent covariate for Cox regression analysis purposes. Adjustment for multiple testing was done in these analyses. A 2-sided P ≤ 0.05 was considered statistically significant. Kaplan-Meier survival analyses

*These authors contributed equally to this work.

Additional supporting information may be found in the online version of this article.

Copyright © 2019 by the American Association for the Study of Liver Diseases.

View this article online at wileyonlinelibrary.com.

DOI 10.1002/lt.25589

Potential conflict of interest: Nothing to report.

Correction statement: In the caption for Fig. 3, the period dates “1998-2002” and “2006-2013” were corrected to “1998-2001” and 2006-2012.” We apologize to the authors and our readers for this error.

liver transplantatiOn, vol. 25, no. 9, 2019 MOusa et al.


were performed comparing overall survival and graft survival in the same 3 age groups: <60, 60-69, and ≥70 years. Statistical analyses were performed using SAS, version 9.4 (SAS Institute, Inc., Cary, NC).

Resultsclinical cHaracteristics OF lt recipients anD DeceaseD DOnOrsAmong 3104 recipients of deceased donor LT during the study period, 823 were excluded for the following reasons: cardiac procedure (n = 11), pancreatoduo-denectomy (n = 9), cholangiocarcinoma (n = 49), combined heart or lung transplant (n = 2), kidney transplant (n = 136), pancreas transplant (n = 4), kid-ney-pancreas transplant (n = 1), partial or split LT (n = 37), DCD transplant (n = 331), and prior LT (n = 300; patients could be excluded for more than 1 reason). The remaining 2281 primary LT patients served as the study cohort. LT recipients had 1 of the following primary diagnoses: cirrhosis due to alco-holic liver disease, viral hepatitis, nonalcoholic fatty liver disease, autoimmune hepatitis, primary sclerosing cholangitis, alpha-1-antitrypsin deficiency, primary biliary cholangitis, hemochromatosis, Wilson’s disease, hepatocellular carcinoma (HCC), fibrolamellar HCC, congenital hepatic fibrosis and Caroli syndrome, Budd-Chiari syndrome, or biliary atresia.

The median recipient age was 56 years (range, 15-80 years; mean ± SD, 56.1 ± 10.1 years; Table 1). The study cohort was divided into 3 groups by recipi-ent age at the time of LT: ≥70 years (n = 162; elderly), 60-69 years (n = 739), and <60 years (n = 1380). Most of the elderly patients (n = 151; 93.2%) received LT in the MELD era. Compared with the 2 other age groups, the elderly recipients had a lower BMI (P = 0.02) and lower physiologic MELD score (P < 0.001). They also had a shorter waiting time than recipients aged 60-69 years. Although not statistically significant, fewer elderly patients were in the ICU or hospital at the time of organ offer for LT (P = 0.22). More elderly patients had HCC as a codiagnosis (P < 0.001), and fewer elderly patients had HCV as their primary liver disease (P < 0.001). The elderly group had a signifi-cantly shorter CIT (P < 0.001) but intermediate WIT and operation time. Overall, they had shorter LOS and a similar rate of ICU requirement after LT compared

with recipients <60 years. The elderly group had an equivalent incidence of previous abdominal surgery as recipients aged 60-69 years and intermediate incidence of portal vein thrombosis.

On the basis of donor characteristics (Table 1), elderly LT recipients were more likely than the younger patients to have donors who were older, particularly aged 70 years or older (P < 0.001); had higher donor risk index (P < 0.001); were female (P = 0.03); were more likely to have diabetes mellitus (P = 0.03); and more often had anoxia and cerebrovascular/stroke as the cause of death (P = 0.01). Donors of elderly recip-ients had a slightly higher BMI than donors of recipi-ents <60 years old but were not more often obese.

recipient anD DOnOr FactOrs assOciateD WitH patient DeatH anD graFt lOss aFter lt

Patient DeathFor the whole cohort, a univariate analysis indicated that older age; need for hospitalization before LT; in-creasing PRBC requirement; longer total operating time, CIT, WIT, and recipient posttransplant hospital LOS; HCC history; need for ICU management after LT; donor UCLA ECD score of ≥2; and cerebrovascu-lar/stroke as the cause of donor death were significantly associated with decreased overall patient survival (all P < 0.05; Fig. 1A; Supporting Table 1A). Specifically, the risk of death increased by 2% per 300-mL increase in PRBC requirement (RR, 1.02; P < 0.001), by 5% per 1-hour increase in CIT (RR, 1.05; P = 0.01), by 17% per 15-minute increase in WIT (RR, 1.17; P < 0.001), and by 6% per 7-day increase in hospital LOS after LT (RR, 1.06; P < 0.001). Recipients with a history of HCC had a 1.33-times higher risk of death than those without (RR, 1.33; P = 0.001), and recip-ients transferred to the ICU after LT had a 1.69-fold increased risk of death compared with those who were not (RR, 1.69; P < 0.001).

On multivariate analysis, greater PRBC require-ment, longer WIT, longer recipient posttransplant hospital LOS, and history of HCC were significantly associated with decreased overall patient survival (P < 0.05; Fig. 1B; Supporting Table 1A). The risk of death in elderly recipients was 1.46 times higher than among recipients <60 years, but this did not reach sta-tistical significance (RR, 1.46; P = 0.06).



taBle 1. recipient and Donor Demographic and clinical information by recipient age group

CharacteristicAll Patients (n = 2281)

Recipient Age at LT

P Value*<60 years (n = 1380) 60-69 years (n = 739) ≥70 years (n = 162)

Recipient

Age, years 56.1 ± 10.1 49.9 ± 8.0 64.1 ± 2.8 71.8 ± 1.9 <0.001

Sex, male 1497 (65.6) 918 (66.5) 465 (62.9) 114 (70.4) 0.11

BMI at listing, kg/m2 29.2 ± 6.3 29.4 ± 6.6 29.0 ± 5.9 28.3 ± 4.8 0.02

BMI ≥30 kg/m2 at listing 886 (38.8) 560 (40.6) 273 (36.9) 53 (32.7) 0.07

Wait time, days 87.1 ± 131.9 82.5 ± 120.2 96.5 ± 154.2 83.3 ± 114.5 0.14

Wait time categories 0.08

≤90 days 1601 (70.2) 997 (72.2) 490 (66.3) 114 (70.4)

91-180 days 370 (16.2) 208 (15.1) 137 (18.5) 25 (15.4)

≥181 days 310 (13.6) 175 (12.7) 112 (15.2) 23 (14.2)

Physiologic MELD score 17.8 ± 9.4 18.5 ± 9.4 16.8 ± 9.7 16.5 ± 8.0 <0.001

Location at LT 0.22

ICU 215 (9.4) 137 (9.9) 69 (9.3) 9 (5.6)

Hospitalized 207 (9.1) 135 (9.8) 59 (8.0) 13 (8.0)

Nonhospitalized 1858 (81.5) 1107 (80.2) 611 (82.7) 140 (86.4)

HCV history 865 (37.9) 622 (45.1) 210 (28.4) 33 (20.4) <0.001

HCC history 578 (25.3) 269 (19.5) 237 (32.1) 72 (44.4) <0.001

PRBCs, mL (n = 2251) 3297.9 ± 3169.3 3273.2 ± 3151.5 3342.0 ± 3050.0 3306.8 ± 3815.1 0.71

CIT, hours (n = 2276) 6.7 ± 1.9 6.8 ± 2.0 6.6 ± 1.8 6.3 ± 1.6 <0.001

WIT, minutes (n = 2276) 32.4 ± 10.7 32.8 ± 11.4 31.6 ± 9.6 32.7 ± 9.9 0.14

Total operating time, hours

4.2 ± 1.4 4.3 ± 1.5 4.1 ± 1.3 4.2 ± 1.3 0.01

Post-LT LOS, days 12.1 ± 21.1 12.4 ± 24.1 11.7 ± 15.7 11.4 ± 13.5 0.42

ICU requirement 203 (8.9) 127 (9.2) 69 (9.3) 7 (4.3) 0.10

Previous abdominal surgery

888 (38.9) 460 (33.3) 351 (47.5) 77 (47.5) <0.001

Portal vein thrombosis 199 (8.7) 97 (7.0) 88 (11.9) 14 (8.6) <0.001

Spontaneous bacterial peritonitis

182 (8.0) 124 (9.0) 51 (6.9) 7 (4.3) 0.14

Primary diagnosis† <0.001

Viral 1349 (59.1) 713 (51.7) 512 (69.3) 124 (76.5)

Nonviral 932 (40.9) 667 (48.3) 227 (30.7) 38 (23.5)

Cancer 634 (27.8) 310 (22.5) 250 (33.8) 74 (45.7) <0.001

Donor

Age, years 48.3 ± 19.0 46.1 ± 18.7 50.9 ± 19.0 54.3 ± 18.0 <0.001

Age categories <0.001

<60 years 1595 (69.9) 1038 (75.2) 466 (63.1) 91 (56.2)

60-69 years 334 (14.6) 173 (12.5) 127 (17.2) 34 (21.0)

≥70 years 352 (15.4) 169 (12.2) 146 (19.8) 37 (22.8)

Sex, male 1278 (56.0) 794 (57.5) 408 (55.2) 76 (46.9) 0.03

BMI, kg/m2 (n = 2277) 28.3 ± 9.7 28.0 ± 8.7 28.7 ± 11.6 28.4 ± 8.0 0.21

BMI ≥30 kg/m2 (n = 2277)

708 (31.0) 418 (30.3) 236 (31.9) 54 (33.3) 0.60

LOS, days (n = 2278) 4.0 ± 10.5 4.1 ± 10.7 4.0 ± 10.9 3.7 ± 4.8 0.74

Donor risk index (n = 2270)

1.6 ± 0.4 1.6 ± 0.44 1.7 ± 0.4 1.7 ± 0.4 <0.001



CharacteristicAll Patients (n = 2281)

Recipient Age at LT

P Value*<60 years (n = 1380) 60-69 years (n = 739) ≥70 years (n = 162)

UCLA ECD score 0.02

0 863 (37.8) 558 (40.4) 256 (34.6) 49 (30.2)

1 1050 (46.0) 607 (44.0) 358 (48.4) 85 (52.5)

≥2 368 (16.1) 215 (15.6) 125 (16.9) 28 (17.3)

Diabetes mellitus 352 (15.4) 192 (13.9) 127 (17.2) 33 (20.4) 0.03

CMV 1580 (69.3) 953 (69.1) 521 (70.5) 106 (65.4) 0.052

HCV 57 (2.5) 40 (2.9) 16 (2.2) 1 (0.6) 0.29

HBV 106 (4.6) 69 (5.0) 30 (4.1) 7 (4.3) 0.30

Cause of death (n = 2277) (n = 1379) (n = 737) (n = 161) 0.01

Anoxia 383 (16.8) 214 (15.5) 135 (18.3) 34 (21.1)

Cerebrovascular/stroke 1193 (52.4) 703 (51.0) 401 (54.4) 89 (55.3)

Head trauma 662 (29.1) 435 (31.5) 193 (26.2) 34 (21.1)CNS tumor/other 39 (1.7) 27 (2.0) 8 (1.1) 4 (2.5)

NOTE: Data are given as mean ± SD or n (%).*χ2 test or t test.†Viral, either HBV or HCV; nonviral, other diagnoses.

taBle 1. Continued

Fig. 1. Forest plots for RR of death and graft loss in the whole cohort. Recipient and donor characteristics associated with recipient overall risk of death on (A) univariate and (B) multivariate analyses. Recipient and donor characteristics associated with recipient overall risk of graft loss on (C) univariate and (D) multivariate analyses.



Graft LossUnivariate analysis of overall graft loss showed that older recipient age; ICU stay before LT; greater PRBC re-quirement; longer total operating time, CIT, WIT, and recipient posttransplant hospital LOS; HCV history; HCC history; need for ICU care after LT; older donor age; higher donor risk index; cerebrovascular/stroke as the cause of donor death; and UCLA ECD score of ≥1 were significantly associated with graft loss (all P < 0.05; Fig. 1C; Supporting Table 1B). On multivariate Cox regression analysis, older recipient age; greater PRBC requirement; longer CIT, WIT, and posttransplant hos-pital LOS; HCC and HCV history; and older donor age remained significantly associated with graft loss (all P < 0.05; Fig. 1D; Supporting Table 1B). Specifically, elderly recipients had a higher risk of graft loss (RR, 1.54; P = 0.001) than recipients younger than 60 years. Recipients who required ICU care after LT were not at higher risk for graft loss (RR, 0.77; P = 0.51).

SubanalysisWe performed a subanalysis for graft and patient sur-vival at 6 and 12 months after LT. On multivariate analysis, the factors associated with patient death at 6 months were CIT, hospitalized and ICU medical status, and donor with diabetes mellitus (Supporting Table 2A), and at 12 months, the factors were CIT, WIT, hospitalized medical status, and donor with di-abetes mellitus (Supporting Table 2B). On multivari-ate analysis, the factors associated with graft failure at 6 months were hospitalized medical status, increased donor risk index, and donor with diabetes mellitus (Supporting Table 2C), and at 12 months, the factors were increased physiologic MELD score, HCV, and donor UCLA ECD score of 1 (Supporting Table 2D).

elDerlY lt recipients Have lOWer patient anD graFt survivalOverall patient and graft survival during a 12-year fol-low-up period after LT differed by age group (Fig. 2). The 5- and 10-year patient survival rates for elderly LT recipients were 70.8% and 43.6%, respectively, compared with 77.2% and 64.6% for recipients aged 60-69 years and 80.7% and 67.6% for those <60 years old (log-rank P = 0.01; Fig. 2A). The 5- and 10-year graft survival rates were 68.4% and 41.7%, 74.9% and 62.6%, and 73.8% and 60.9% for those ≥70, 60-69, and <60 years old, respectively (log-rank P = 0.04; Fig. 2B).

To understand the evolution of LT for elderly candi-dates, we categorized LT activity into different periods correlating to 1998-2001 (pre-MELD era), 2002-2005 (MELD and Share 15 era), 2006-2012 (pre–Share 35 era), and 2013-2016 (Share 35 era). For the overall cohort, patient and graft survival significantly improved in later time periods (P < 0.001; Fig. 3A,B); however, among the elderly recipients, patient and graft survival remained relatively stable throughout the study peri-ods of LT at our center (Fig. 3C, P = 0.86; Fig. 3D, P = 0.45).

risK FactOrs assOciateD WitH DeatH anD graFt lOss in elDerlY lt recipientsWe further focused on the elderly group. Univariate analysis of recipient and donor characteristics as-sociated with death specifically among elderly LT recipients showed that higher recipient BMI at listing, greater PRBC requirement, and longer WIT were sig-nificantly associated with death overall (all P < 0.05; Fig. 4A; Supporting Table 3A). On multivariate analysis, greater PRBC requirement and longer WIT remained significant (both P < 0.001), and donor CMV positiv-ity became significant (P = 0.006; Fig. 4B; Supporting Table 3A). The risk of death increased by 4% with an in-crease in the PRBC requirement by 300 mL (RR, 1.04; P < 0.001) and by 2.44 times with a 15-minute increase in WIT (RR, 2.44; P < 0.001).

Univariate analysis of recipient and donor character-istics associated with graft loss among elderly LT recip-ients showed that higher recipient BMI, greater PRBC requirement, longer WIT, and head trauma/central nervous system (CNS) tumor/other as the donor cause of death were significantly associated with decreased graft survival (all P < 0.05; Fig. 4C; Supporting Table 3B). On multivariate Cox regression analysis, greater PRBC requirement and longer WIT remained significantly associated with decreased graft survival (both P < 0.05; Fig. 4D; Supporting Table 3B). The risk of graft loss increased by 73% for each 15-minute increase in WIT (RR, 1.73; P = 0.004).

We also analyzed other factors that could have influenced outcomes in elderly recipients: DCD and HCC. Patient and graft survival in elderly patients who received a DCD LT (n = 19) was significantly greater than in patients without DCD LT (P = 0.01 and P = 0.03, respectively; Supporting Fig. 1). In this study, 81 elderly recipients had HCC, most of whom were within the Milan criteria. We observed



no disadvantage in patient and graft outcomes among the elderly recipients with HCC versus those without HCC (Supporting Fig. 2).

elDerlY lt recipients regaineD Years OF liFe tOWarD tHeir liFe eXpectancYA survival analysis for LT recipients, alongside patients who were denied LT by the selection committee at our center and age-equivalent persons in the general US

population, showed that in each age group, LT recipients clearly benefited from the transplant. Patients who were not accepted for transplant died of disease within a short time (Fig. 5). Similar to the younger patients (Fig. 5A,B), the elderly patients had restored life spans toward those of the age-equivalent population as compared with those denied LT (Fig. 5C). Interestingly, all LT recipients, re-gardless of age at the time of LT, had a gap of 20%-30% below the expected life span of the general population.

We next assessed whether each incremental year of age among the elderly recipients affected outcomes. Kaplan-Meier analysis for patients aged 70-75 years

Fig. 2. Kaplan-Meier curves for (A) overall patient survival and (B) overall graft survival according to recipient age group.



showed no significant difference in patient or graft sur-vival by age (log-rank P = 0.32 for both; Fig. 6). Thus, there appeared to be no incremental negative effect of age at LT among elderly patients in this cohort.

DiscussionThe role of LT in elderly patients (≥70 years) with acute or chronic liver failure is not well defined. In this study, we show that 162 septuagenarians who received LT at our center clearly benefited from a significant extension of life span. Our results support the proposi-tion that LT provides select septuagenarians an effec-tive means of restoring their lives toward an expected life span relative to their ages.

The 5- and 10-year patient survival rates among adult LT recipients <70 years old in our cohort are comparable to those in other large-volume cen-ters(8,14,21); however, there are few reports on LT in septuagenarians. Lipshutz et al.(9) reported 62 cases in 2007, which showed 5- and 10-year patient survival rates of 47.1% and 39.7%, respectively; their recent abstract updated the total to 140 LTs in septuagenar-ians from 1984 through 2015 and showed a 5-year overall survival rate of 56%.(22) In a review of UNOS data on 143 septuagenarian recipients in 2009, the overall survival rate was 55.2% at 5 years after LT.(18) At our center, elderly recipients accounted for 7.1% (162/2281) of primary LTs in our study, and their overall 5- and 10-year survival rates were 70.8% and 43.6%, respectively (graft survival rates were 68.4%

Fig. 3. Kaplan-Meier curves for overall and graft survival by period of allocation policy. Periods were categorized according to pre-MELD era (1998-2001), MELD and Share 15 era (2002-2005), pre–Share 35 era (2006-2012), and Share 35 era (2013-2016). For the entire cohort, graphs show overall (A) patient and (B) graft survival. For elderly recipients only (age ≥70 years), graphs show overall (C) patient and (D) graft survival.



and 41.7%, respectively). This 5-year survival rate compares favorably to that in reports on elderly LT recipients (47%-62%).(4,9,18,19) Our results are also consistent with previous findings that, although they have higher wait-list mortality rates, lower likelihood of transplant, and increasing posttransplant mortal-ity rates, elderly LT recipients derive the same post-transplant survival benefits as younger patients.(4) In addition, patient and graft survival associated with LT improved over time from the pre-MELD era to Share 15, pre-Share 35, and Share 35 for all age groups on average. However, patient and graft sur-vival remained relatively stable in septuagenarians throughout the study periods, possibly because of the small sample size. There appeared to be no incre-mental negative effect of age at LT among elderly patients aged 70-75 years, with no significant dif-ference in patient or graft survival. This further sup-ports the role of LT in elderly recipients.

We sought to define the role of LT in elderly recip-ients in relation to their anticipated life expectancy, as defined by age-equivalent members of the general US population. We examined the survival of not only LT recipients but also candidates denied LT. Across the 3 age groups, we confirmed that patients without LT evaluated at our center generally have an abbreviated life course and die within 1 year, whereas LT recip-ients clearly benefited from transplant. These results

are consistent with reports showing generally increased years of life after LT.(5,7,8) As expected according to the general life span, the overall survival of elderly LT recipients is inferior to that of younger recipients; how-ever, elderly recipients of a successful LT regained their life spans. Importantly, both elderly and younger recip-ients still have a 20%-30% loss of potential life span beyond the first year after LT. Our findings confirm reports from the United Kingdom and Norway.(7,8) These results corroborate the importance of further optimization of posttransplant care, regardless of age, to achieve normalization of the expected life span to that of the general population.

In the process of selecting patients with end-stage liver diseases for LT, we do not consider age an abso-lute contraindication, in accordance with the guide-lines from the American Association for the Study of Liver Diseases.(23,24) However, it is expected that eligible elderly candidates are functional and have the cardiovascular ability to tolerate the operation. At our center, elderly recipients accepted for LT did not dif-fer from those aged <60 years in medical comorbid conditions, including cardiovascular, pulmonary, and metabolic diseases. In a prior report, we showed that elderly patients did not differ from younger patients in biliary, vascular, and bleeding complications; the need for mechanical ventilation; length of ICU and hospital stays; or readmission after LT.(10) Still, we

Fig. 4. Forest plots for RR of death and graft loss in elderly recipients (age ≥70 years). Recipient and donor characteristics associated with recipient overall risk of death on (A) univariate and (B) multivariate analyses. Recipient and donor characteristics associated with recipient overall risk of graft loss on (C) univariate and (D) multivariate analyses.



recognize that there is more to learn and refine in the evaluation and selection of suitable elderly candidates for lifesaving LT.

Although our results are encouraging for elderly patients with end-stage liver diseases, we continue to use caution in identifying candidates who would derive the most benefit from transplant.(11,25) With advances in medicine and science, age is no longer the dominant factor as an independent or absolute criterion of eligibility for LT.(1,4,19,26) However, each transplant center may approach the elderly population individually on the basis of their surgical, medical, and integrative capacity. To that extent, our results are not necessarily generalizable to all other centers with different clinical protocols and approaches. We observe that careful selection of elderly candidates who do not have substantial comorbid conditions is a key to successful outcomes after LT. Our results suggest that in addition to considering the standard cardiovascular pulmonary evaluation, we should be mindful of the recipient’s anatomical and surgi-cal factors that are associated with increased blood transfusion and prolonged WIT during implantation of the allograft. These factors reflect the surgical difficulties that decrease both graft and patient out-comes among elderly recipients.

Several important factors did not affect outcomes. We previously showed that DCD LT resulted in simi-lar patient and graft outcomes to those of conventional donation after brain death allografts.(20,27) Although in this study only 19 DCD livers were used among the elderly recipients, these patients had excellent out-comes. Another report showed that HCC did not affect the outcomes of elderly patients after LT,(18) and we observed a similar finding in this study.

Limitations of this study include its retrospec-tive approach. Prospective future studies are needed. The single-center experience also limits its general applicability. However, its strength resides in the rel-ative consistency of clinical practice, including the selection process, transplant surgical approach, and pretransplant and posttransplant multidisciplinary management, as defined by protocols at our trans-plant program. Thus, this medically and surgically homogeneous practice from a single center may pro-vide a solid basis for considering the elderly for LT. We compared the denied candidates for each study group to illustrate that the elderly candidates and the younger age groups who were denied LT had poor survival rates; however, they were neither necessar-ily equivalent nor homogeneous groups for a strict comparison. Thus, we cannot generalize these com-parisons to candidates elsewhere. In this study, we

Fig. 5. Kaplan-Meier curves for overall survival by recipient age. Survival among the adult LT recipients in comparison with survival of candidates who were denied LT and the expected survival among the age-matched general population. (A) LT recipients, denied patients, and general population aged <60 years old. (B) LT recipients, denied patients, and general population aged 60-69 years old. (C) LT recipients, denied patients, and general population aged ≥70 years old.



did not directly assess quality of life in elderly LT recipients. Although the selection process demands functional capability of all elderly candidates, their quality of life after LT requires further evaluation.

We conclude that in this era of aging populations, select elderly patients with end-stage liver diseases can benefit from LT. Advancing knowledge of the increas-ing role of LT in elderly patients will be important for enhancing their health care, restoring their quality of life, and realizing their full potential life spans.

Acknowledgment: We thank the members of multidis-ciplinary teams at Mayo Clinic, Jacksonville, FL, for their clinical contributions.

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Evolving Role of Liver Transplantation in Elderly Recipients · 2020. 1. 17. · 4Information Technology, Mayo Clinic, Jacksonville, FL The need for liver transplantation (LT) among