Abstract
Background.
This study aims to evaluate the impact of obesity on post–liver transplant outcomes stratified by low- and high-performance status.
Methods.
Patients undergoing liver transplantation between 2006 and 2023 were identified in the United Network for Organ Sharing data set. Patients with severe obesity body mass index ([BMI] ≥40 kg/m2) and super obesity (BMI >50 kg/m2) were compared with those with lower BMI on perioperative and long-term outcomes stratified by preoperative performance status.
Results.
Severe obesity has a significant negative impact on perioperative and long-term outcomes on the low-performance group (LPG). This effect was not observed in the high-performance group. Five-year survival in the high-performance group was 81.7%, compared with 77.9% in the LPG. The multivariable analysis revealed that severe obesity in the LPG increased early graft loss by 53%, and 30- and 90-d mortality by 57% and 50%, respectively (P < 0.001). Severe obesity significantly impacted overall graft survival but did not affect long-term patient survival. When advanced age was combined with severe obesity in the LPG, our analysis showed a 2.3-fold increased risk of early graft loss (P = 0.01) and 83%, 90-d perioperative mortality (P < 0.001). Overall long-term graft and patient survival were decreased by 56% and 59%, respectively, in the LPG (P < 0.001).
Conclusions.
Severe obesity in patients with a low-performance status before transplantation significantly increases the risk of poor perioperative and long-term outcomes. Interestingly, this effect is not seen in patients with high-performance scores. Additionally, the combination of severe obesity and advanced age in low-performance status patients may have a compounded negative effect on posttransplant survival.
Patients with cirrhosis face considerable health challenges, including high morbidity and increased risk of mortality.1 The progression of the liver disease often leads to complications from portal hypertension and a higher rate of life-threatening infections.2 As a result, cirrhosis leads to a poor quality of life and significantly shortens life expectancy. Liver transplantation (LT) is the best treatment option for selected patients with advanced liver disease and certain hepatobiliary malignancies. Although LTs are generally associated with improved survival and quality of life, they come with significant risks and morbidity.3,4 A thorough medical and psychosocial evaluation process is performed to determine which patients have the best potential benefit of LT that outweighs the risks. Although morbid or severe obesity and functional status have played a role in determining candidacy for waitlisting for orthotopic liver transplantation , providers have often relied on the “eyeball” test rather than objective data.
Severe obesity was once considered a relative or absolute contraindication for transplantation in some centers due to the increased risk of peri- and postoperative complications.5 However, the data regarding LT outcomes in obese populations remain controversial. Several studies have suggested an increased risk of mortality in the morbid or super obese groups, whereas other reports have observed no significant differences in long-term outcomes.6
The Karnofsky Performance Score (KPS) is a basic assessment scale for evaluating functional status.7 This measure, commonly used in oncology and in patients with chronic diseases, has shown to be a reliable tool for assessing treatment tolerance and predicting overall surgical outcomes.8-12 Frailty and low-performance scores as measured by KPS have been associated with worse short- and long-term patient and graft survival after liver LT.13 Several models have also been validated to assess posttransplant mortality, including the Model of End-stage Liver Disease (MELD) and the Child-Pugh score, in which frailty assessment is not included.
LTs in the elderly typically show lower graft and patient survival rates. However, favorable outcomes and survival have still been reported in this patient population.14 The impact of severe obesity and advanced age in liver disease patients with high- and low-performance status has not been investigated.
In this study, we aim to evaluate the effect of severe obesity and advanced age in cirrhotic patients with low- and high-performance status on perioperative and long-term transplant outcomes.
MATERIALS AND METHODS
Study Design, Setting, and Participants
This retrospective cohort study analyzed data from the United Network for Organ Sharing (UNOS) data set from 2006 to 2023. All patients who underwent LT during this period were identified. Before 2006, functional status was not consistently reported by UNOS and those patients were excluded from this analysis. Retransplantation, those younger than 18 y, on mechanical ventilation, and multivisceral transplants, including simultaneous liver-kidney transplants, were also excluded. Demographic preoperative variables collected included age, sex, race, ethnicity, body mass index (BMI), history of diabetes, presence of encephalopathy, creatinine, total bilirubin, international normalized ratio, MELD score, preoperative KPS at the time of transplant, and history of portal vein thrombosis. KPS scores were stratified into low, intermediate, and high KPS groups (low [10%–40%], intermediate [50%–70%], and high [80%–100%]). We grouped the intermediate and high groups into a single group (high KPS) to assess differences between these 2 groups. Donor and transplant-specific data, such as cold ischemia time, donor type (brain dead, circulatory death, and living donor), donor age, and hepatic artery thrombosis as a cause of graft failure, were also captured. The primary outcomes of interest were long-term patient and graft survival, as well as perioperative outcomes, including EGL (<7 d), length of hospital stay (LOS), and 30- and 90-d mortality assessed in the low and high KPS groups. We performed a subsequent analysis to assess the impact of the combination of advanced age (65 y and older) and severe obesity (BMI ≥40 kg/m2) on long-term and perioperative outcomes. We selected the age of 65 y as the cutoff in our analysis based on recent data showing a significant increase in the percentage of LTs performed in this age group.15 We performed a secondary multivariable analysis for all outcomes to assess the additional risk associated with super obesity compared with severe obesity.
Statistical Analysis
Data of variables after a normal distribution were expressed as means and SDs. When a nonnormal distribution was identified, the data were reported as median and interquartile range. Depending on the distribution, the T test and median test were used to compare the means and medians of the variables. Patient and graft survival was calculated using Kaplan-Meier product limit estimates and compared using the log-rank test. The Cox proportional hazards model was used to assess predictors of long-term graft and patient survival using backward selection of significant variables. Logistic regression was performed to identify predictors of early graft loss (EGL) at 7 d, perioperative mortality at 30 and 90 d, and prolonged LOS (>median). Missing data for continuous variables were entered with the median or mean using the SPSS automatic imputation method, depending on the distribution. For most variables, the percentage of missing data was <10% (24 cases with missing BMI were also excluded). Statistical analysis was performed using the SPSS software version 28.0 (SPSS Inc, Armonk, NY).
RESULTS
Patient Demographics and Characteristics
A total 100 001 patients undergoing LT were included in this analysis. The demographics and patient characteristics are summarized in Table 1. Severe obesity (BMI ≥40 kg/m2) was reported in 4115 patients (4.1%). The median age for those with a BMI of ≥40 kg/m2 was 53 versus 55.3 for the lower BMI group. In the severe obesity group, 45.5% had low KPS at the time of transplant versus 34.9% in the lower BMI group (P < 0.001). The severe obese group had significantly higher creatinine (1.2 versus 1 mg/dL; P < 0.001), total bilirubin (5.3 versus 3.6; P < 0.001), international normalized ratio (1.9 versus 1.6; P < 0.001), and MELD score (25 versus 20; P < 0.001) at the time of transplant.
TABLE 1.
Univariate analysis of patients with severe obesity vs lower BMIs
| Variable | BMI <40 kg/m2 (N = 95 886) | BMI ≥40 kg/m2 (N = 4115) | P |
|---|---|---|---|
| Recipient | |||
| Age | 55.3 ± 10.7 | 53.0 ± 9.9 | <0.001 |
| Sex | |||
| Male | 63 964 (66.7%) | 2257 (54.8%) | <0.001 |
| Female | 31 922 (33.3%) | 1858 (45.2%) | |
| Race | |||
| White | 68 956 (71.9%) | 2998 (72.9%) | <0.001 |
| Black | 7340 (7.7%) | 359 (8.7%) | |
| Others | 19 590 (20.4%) | 758 (18.4%) | |
| Ethnicity | |||
| Non-Hispanic | 81 831 (85.3%) | 3463 (84.2%) | 0.035 |
| Hispanic | 14 055 (14.7%) | 652 (15.8%) | |
| KPS groups | |||
| Low | 33 445 (34.9%) | 1874 (45.5%) | <0.001 |
| High | 62 441 (65.1%) | 2241 (54.4) | |
| Diabetes status | |||
| No | 70 433 (73.5%) | 2646 (64.3%) | <0.001 |
| Yes | 25 024 (26.1%) | 1453 (35.3%) | |
| Unknown | 429 (0.4%) | 16 (0.4%) | |
| Presence of encephalopathy | |||
| None | 35 931 | 1240 | |
| 1–2 | 50 008 | 2363 | |
| 3–4 | 9542 | 500 | |
| NA | 393 | 12 | |
| Cold ischemic time, h | 5.9 (4.5-7.5) | 6.0 (4.8-7.5) | <0.001 |
| Creatinine | 1.0 (0.8-1.5) | 1.2 (0.9-1.9) | <0.001 |
| Total bilirubin | 3.6 (1.7-9.5) | 5.3 (2.3-13.6) | <0.001 |
| INR | 1.6 (1.3-2.2) | 1.9 (1.4-2.5) | <0.001 |
| MELD | 20.0 (13.0-29.0) | 25.0 (17.0-34.0) | <0.001 |
| Portal vein thrombosis | |||
| No | 83 628 (87.2%) | 3569 (86.7%) | 0.073 |
| Yes | 11 691 (12.2%) | 531 (12.9%) | |
| Unknown | 567 (0.6%) | 15 (0.4%) | |
| Donor | |||
| Donor type | |||
| Deceased | 90 905 (94.8%) | 4029 (97.9%) | <0.001 |
| Living | 4981 (5.2%) | 86 (2.1%) | |
| Age | 42.2 ± 16.2 | 42.1 ± 15.5 | 0.701 |
| Outcome | |||
| Early graft loss | |||
| Yes | 1604 (1.7%) | 102 (2.5%) | <0.001 |
| 30-d mortality | |||
| Yes | 1933 (2.0%) | 135 (3.3%) | <0.001 |
| 90-d mortality | |||
| Yes | 3302 (3.4%) | 217 (5.3%) | <0.001 |
| HAT | 505 (0.5%) | 18 (0.4%) | 0.437 |
BMI, body mass index; HAT, hepatic artery thrombosis as cause of graft failure; INR, international normalized ratio; KPS, Karnofsky Performance Score; MELD, Model for End-stage Liver Disease; PVT, portal vein thrombus.
On univariate analysis, early allograft loss (7 d) was significantly higher in those with severe obesity (2.5 versus 1.7; P < 0.001). Thirty-day mortality and 90-d mortality were also significantly higher in those with severe obesity (3.3% versus 2% and 5.3% versus 3.4% respectively; P < 0.001). The LOS was prolonged in the severe obesity group (11 versus 9 d; P < 0.001). There were no differences in hepatic artery thrombosis as the cause of graft failure between the 2 groups. Patients with high-performance scores had a 5-y survival rate of 81.7% compared with 77.9% in the low KPS group (P < 0.001). In patients older than 65 y with severe obesity and a low KPS, the 5-y survival rate decreased to 69.2%.
Impact of Severe Obesity on Perioperative and Long-term Outcomes: A Comparison Between Low and High KPS Groups
After controlling for statistically significant variables, the logistic regression analysis demonstrated that within the low-performance group, those with severe obesity had a 53% increased risk of EGL when compared with lower BMIs (P = 0.002; odds ratio [OR], 1.53; 95% confidence interval [CI], 1.16-2.03). Severe obesity significantly increased the risk of 30- and 90-d mortality by 57% and 50%, respectively (P < 0.001; OR, 1.57; 95% CI, 1.24-1.98 and P < 0.001; OR, 1.50; 95% CI, 1.25-1.81, respectively).
Cox proportional hazard model analysis demonstrated that within the patients with low-performance status, those with severe obesity had 13% increased risk of graft loss compared with those with lower BMIs (P = 0.006; hazard ratio, 1.13; 95% CI, 1.03-1.24) with no significant impact on long-term patient survival. Interestingly, our analysis also did not demonstrate a significant effect of severe obesity in the high-performance group in any of the measured peri- or postoperative outcomes, EGL, 30- to 90-d mortality, and long-term graft and patient survival (Tables 2–6). A secondary analysis for all outcomes was performed to evaluate the additional risk associated with super obesity (BMI >50 kg/m2) in the low KPS cohort. We found that super obesity is associated with 2.4- and 2.5-fold increased risk of 30- and 90-d mortality, respectively (OR, 2.46; 95% CI, 1.19-5.11, OR, 2.5; 95% CI, 1.39-4.49).
TABLE 2.
Multivariate analysis of early graft loss in the low-performance group
| Variables | P | OR | 95% CI | |
|---|---|---|---|---|
| Lower | Upper | |||
| Recipient age, y | ||||
| ≥65 | 0.011 | 1.309 | 1.063 | 1.612 |
| Ref. <65 | – | – | – | – |
| Recipient sex | ||||
| Male | 0.046 | 0.857 | 0.736 | 0.998 |
| Ref. female | – | – | – | – |
| Ethnicity | ||||
| Black | 0.021 | 1.343 | 1.045 | 1.726 |
| Others | 0.285 | 1.105 | 0.920 | 1.326 |
| Ref. White | – | – | – | – |
| BMI, kg/m2 | ||||
| ≥40 | 0.002 | 1.538 | 1.163 | 2.032 |
| Ref. <40 | – | – | – | – |
| Diabetes | ||||
| Yes | 0.071 | 1.168 | 0.987 | 1.382 |
| Ref. no | – | – | – | – |
| Encephalopathy at transplant | ||||
| 1–2 | 0.051 | 0.835 | 0.697 | 1.001 |
| 3–4 | 0.484 | 0.920 | 0.727 | 1.163 |
| NA | 0.587 | 1.379 | 0.432 | 4.395 |
| Ref. none | – | – | – | – |
| MELD Score | 0.048 | 1.008 | 1.000 | 1.016 |
| PVT | ||||
| Yes | <0.001 | 1.620 | 1.338 | 1.961 |
| Unknown | 0.006 | 2.734 | 1.336 | 5.594 |
| No | – | – | – | – |
| Donor type | ||||
| Deceased | 0.232 | 1.339 | 0.829 | 2.162 |
| Ref. living | – | – | – | – |
| Donor age | 0.015 | 1.006 | 1.001 | 1.011 |
| HAT | ||||
| Yes | <0.001 | 10.664 | 7.109 | 15.997 |
| Others | – | – | – | – |
BMI, body mass index; CI, confidence interval; HAT, hepatic artery thrombosis as cause or graft failure; MELD, Model for End-stage Liver Disease; OR, odds ratio; PVT, portal vein thrombus; Ref, reference group.
TABLE 6.
Multivariate analysis of patient survival in the low-performance group
| Variables | P | OR | 95% CI | |
|---|---|---|---|---|
| Lower | Upper | |||
| Recipient age, y | ||||
| >65 | <0.001 | 1.601 | 1.512 | 1.696 |
| Ref. <65 | – | – | – | – |
| Recipient sex | ||||
| Male | <0.001 | 1.148 | 1.098 | 1.199 |
| Ref. female | – | – | – | – |
| Ethnicity | ||||
| Black | <0.001 | 1.209 | 1.126 | 1.299 |
| Others | <0.001 | 0.853 | 0.808 | 0.901 |
| Ref. White | – | – | – | – |
| BMI, kg/m2 | ||||
| ≥40 | 0.067 | 1.093 | 0.994 | 1.202 |
| Ref. <40 | – | – | – | – |
| Diabetes | ||||
| Yes | <0.001 | 1.366 | 1.305 | 1.431 |
| Ref. no | – | – | – | – |
| Encephalopathy at transplant | ||||
| 1–2 | 0.197 | 1.035 | 0.982 | 1.091 |
| 3–4 | <0.001 | 1.154 | 1.078 | 1.235 |
| NA | 0.350 | 1.145 | 0.862 | 1.522 |
| Ref. none | – | – | – | – |
| MELD Score | 0.131 | 0.998 | 0.996 | 1.001 |
| PVT | ||||
| Yes | <0.001 | 1.224 | 1.155 | 1.298 |
| Unknown | 0.817 | 1.031 | 0.797 | 1.332 |
| Ref. no | – | – | – | – |
| Donor type | ||||
| Deceased | 0.544 | 1.049 | 0.899 | 1.223 |
| Ref. living | – | – | – | – |
| Donor age | <0.001 | 1.007 | 1.005 | 1.008 |
| HAT | ||||
| Yes | <0.001 | 3.661 | 2.711 | 4.944 |
| Ref. others | – | – | – | – |
CI, confidence interval; HAT-COGF, hepatic artery thrombosis as cause or graft failure; MELD, Model for End-stage Liver Disease; OR, odds ratio; PVT, portal vein thrombus.
TABLE 3.
Multivariate analysis of 30-d mortality in the low-performance group
| P | OR | 95% CI | ||
|---|---|---|---|---|
| Variables | Lower | Upper | ||
| Recipient age, y | ||||
| ≥65 | <0.001 | 1.546 | 1.306 | 1.829 |
| Ref. <65 | – | – | – | – |
| Recipient sex | ||||
| Male | 0.631 | 0.969 | 0.851 | 1.103 |
| Ref. female | – | – | – | – |
| Ethnicity | ||||
| Black | 0.005 | 1.356 | 1.097 | 1.676 |
| Others | 0.504 | 1.054 | 0.903 | 1.232 |
| Ref. White | – | – | – | – |
| BMI, kg/m2 | ||||
| ≥40 | <0.001 | 1.574 | 1.246 | 1.989 |
| Ref. <40 | – | – | – | – |
| Diabetes | ||||
| Yes | 0.054 | 1.150 | 0.998 | 1.326 |
| Ref. no | – | – | – | – |
| Encephalopathy at transplant | ||||
| 1–2 | 0.439 | 0.939 | 0.800 | 1.102 |
| 3–4 | 0.035 | 1.232 | 1.015 | 1.497 |
| NA | 0.464 | 1.458 | 0.531 | 4.005 |
| Ref. none | – | – | – | – |
| MELD Score | <0.001 | 1.016 | 1.009 | 1.023 |
| PVT | ||||
| Yes | <0.001 | 1.748 | 1.491 | 2.048 |
| Unknown | 0.032 | 2.093 | 1.064 | 4.116 |
| Ref. no | – | – | – | – |
| Donor type | ||||
| Deceased | 0.335 | 1.248 | 0.796 | 1.955 |
| Ref. living | – | – | – | – |
| Donor age | 0.022 | 1.005 | 1.001 | 1.009 |
| HAT | ||||
| Yes | <0.001 | 3.120 | 1.793 | 5.429 |
| Ref. others | – | – | – | – |
BMI, body mass index; CI, confidence interval; HAT, hepatic artery thrombosis as cause or graft failure; MELD, Model for End-stage Liver Disease; OR, odds ratio; PVT, portal vein thrombus; Ref, reference group.
TABLE 4.
Multivariate analysis of 90-d mortality in the low-performance group
| Variables | P | OR | 95% CI | |
|---|---|---|---|---|
| Lower | Upper | |||
| Recipient age, y | ||||
| ≥65 | <0.001 | 1.622 | 1.425 | 1.846 |
| Ref. <65 | – | – | – | – |
| Recipient sex | ||||
| Male | 0.986 | 1.001 | 0.905 | 1.107 |
| Ref. female | – | – | – | – |
| Ethnicity | ||||
| Black | 0.028 | 1.209 | 1.020 | 1.433 |
| Others | 0.203 | 0.923 | 0.815 | 1.044 |
| Ref. White | – | – | – | – |
| BMI, kg/m2 | ||||
| ≥40 | <0.001 | 1.505 | 1.250 | 1.812 |
| Ref. <40 | – | – | – | – |
| Diabetes | ||||
| Yes | <0.001 | 1.245 | 1.116 | 1.388 |
| Ref. no | – | – | – | – |
| Encephalopathy at transplant | ||||
| 1–2 | 0.926 | 1.006 | 0.887 | 1.140 |
| 3–4 | 0.002 | 1.273 | 1.093 | 1.483 |
| NA | 0.012 | 2.341 | 1.207 | 4.542 |
| Ref. none | – | – | – | – |
| MELD Score | <0.001 | 1.016 | 1.011 | 1.021 |
| PVT | ||||
| Yes | <0.001 | 1.566 | 1.379 | 1.778 |
| Unknown | 0.052 | 1.758 | 0.994 | 3.108 |
| Ref. no | – | – | – | – |
| Donor type | ||||
| Deceased | 0.269 | 1.219 | 0.858 | 1.733 |
| Ref. living | – | – | – | – |
| Donor age | 0.002 | 1.005 | 1.002 | 1.008 |
| HAT | ||||
| Yes | <0.001 | 2.876 | 1.812 | 4.566 |
| Ref. others | – | – | – | – |
CI, confidence interval; HAT, hepatic artery thrombosis as cause or graft failure; MELD, Model for End-stage Liver Disease; OR, odds ratio; PVT, portal vein thrombus; Ref, reference group.
TABLE 5.
Multivariate analysis of graft survival in the low-performance group
| Variables | P | OR | 95% CI | |
|---|---|---|---|---|
| Lower | Upper | |||
| Recipient age, y | ||||
| 65 | <0.001 | 1.477 | 1.395 | 1.563 |
| Ref. <65 | – | – | – | – |
| Recipient sex | ||||
| Male | <0.001 | 1.135 | 1.088 | 1.185 |
| Ref. female | – | – | – | – |
| Ethnicity | ||||
| Black | <0.001 | 1.260 | 1.177 | 1.349 |
| Others | <0.001 | 0.859 | 0.849 | 0.943 |
| Ref. White | – | – | – | – |
| BMI, kg/m2 | ||||
| ≥40 | <0.006 | 1.136 | 1.037 | 1.243 |
| Ref. <40 | – | – | – | – |
| Diabetes | ||||
| Yes | <0.001 | 1.290 | 1.233 | 1.349 |
| Ref. no | – | – | – | – |
| Encephalopathy at transplant | ||||
| 1–2 | 0.738 | 1.009 | 0.959 | 1.061 |
| 3–4 | <0.001 | 1.135 | 1.063 | 1.212 |
| NA | 0.088 | 1.266 | 0.966 | 1.660 |
| Ref. none | – | – | – | – |
| MELD Score | 0.159 | 0.998 | 0.996 | 1.001 |
| PVT | ||||
| Yes | <0.001 | 1.215 | 1.148 | 1.286 |
| Unknown | 0.652 | 1.060 | 0.823 | 1.364 |
| Ref. no | – | – | – | – |
| Donor type | ||||
| Deceased | 0.001 | 1.257 | 1.097 | 1.440 |
| Ref. living | – | – | – | – |
| Donor age | <0.001 | 1.008 | 1.006 | 1.009 |
| HAT | ||||
| Yes | <0.001 | 12.816 | 11.015 | 14.911 |
| Ref. others | – | – | – | – |
CI, confidence interval; HAT-COGF, hepatic artery thrombosis as cause or graft failure; MELD, Model for End-stage Liver Disease; OR, odds ratio; PVT, portal vein thrombus.
Combined Effect of Severe Obesity and Age on Perioperative Outcomes and Long-term Outcomes in Low KPS Patients Undergoing LT
The combination of severe obesity and age 65 y or older within the low KPS group demonstrated a 2.3-fold increased risk of EGL when compared with younger patients with lower BMI (P < 0.001; OR, 2.36; 95% CI, 1.15-4.85). Similarly, it also significantly increased the risk of 90-d perioperative mortality by 83% (P < 0.001; OR, 1.83; 95% CI, 1.073-3.14). Those in elderly group with severe obesity and low-performance status had 56% increased risk of graft loss and 59% of decreased patient survival (P < 0.001; OR, 1.56; 95% CI, 1.19-2.03 and P < 0.001; OR, 1.59; 95% CI, 1.21-2.09, respectively; Figures 1 and 2). The LOS was also significantly longer in the elderly obese group (P < 0.03; OR, 1.45; 95% CI, 1.03-2.04).
FIGURE 1.
Graft survival in patients with severe obesity and age 65 y or older within the low-performance group. BMI, body mass index.
FIGURE 2.
Patient survival in patients with severe obesity and age 65 y or older within the low-performance group. BMI, body mass index.
DISCUSSION
Obesity is a chronic disease associated with increased risk of diabetes, cardiovascular disease, and cancer, among others.3,16,17 In the United States, the prevalence of overall obesity has dramatically increased from 22.9% to 41.9% from 1988 to 2020, and the prevalence of severe obesity has increased from 5.7% to 9.2% between 2007 and 2020.18 Due to high obesity rates in the general population and its link with metabolic dysfunction–associated steatotic liver disease, transplant centers are now evaluating a substantial number of patients with severe obesity. Several reports indicate a significant increase in the number of patients with morbid or severe obesity undergoing transplantation in the United States, making up more than one-third of all patients receiving a LT.6,19-21
In surgery, severe obesity has been associated with a higher risk of postoperative complications across various general surgery procedures.6,19,22 Yet, the relationship between obesity and morbidity risk after LT remains controversial. Studies have found increased rates of wound infections, respiratory and cardiovascular complications, earlier cancer recurrence, longer periods of hospitalization, and increased intensive care unit stay in obese populations undergoing LT.5,6,23-28 Conversely, other researchers have found no significant differences in postoperative complications, intensive care unit and hospital LOS. Similarly, the evidence regarding obesity and posttransplant mortality is conflicting. In a systematic review by Barone et al6, 5 of 16 studies reported decreased patient survival, with 3 of those showing higher mortality rates at 30 d, 2 y, and 5 y. Other reports specifically investigated the impact of severe obesity (BMI >40 kg/m2) but have produced inconsistent results. Our group evaluated the impact of super obesity (BMI >50 kg/m2) in patients undergoing LT, demonstrating a significant increase of >50% in the risk of 30-d mortality and long-term graft and patient survival.28
The relationship between obesity and low-performance status in the general population is well documented, particularly on the effects on physical function and mobility, cardiorespiratory fitness, mental health, and quality of life. The KPS, used to assess patients’ functional status, has also been used to predict postoperative outcomes, including those after transplant. Several studies have reported the utility of the performance status assessment with KPS on patients with cirrhosis.13,29 Thuvash et al30 conducted a study evaluating pretransplant KPS as a predictor of long-term survival after transplantation. They found that a low pretransplant KPS, along with a lack of improvement in KPS within 3–12 mo posttransplant, was associated with poorer long-term patient and graft survival. Additionally, poor outcomes have also been observed in candidates for simultaneous liver and kidney transplants with low KPS scores.31 Our study revealed a distinct impact of severe obesity on perioperative and long-term transplant outcomes varying by patients’ performance status. In fact, patients in the high-performance group were minimally or not affected by severe obesity after controlling for multiple factors, demonstrating similar outcomes to those in the lower BMI classes. This differential effect of severe obesity on posttransplant outcomes in patients stratified by performance status is intriguing. Notably, in the low-performance group, BMI ≥40 kg/m2 had 53% increased risk of EGL, as well as 50% and 57% of worse long-term graft and patient survival after LT, respectively. Additionally, in patients older than 65 y with severe obesity, we observed an additive deleterious effect on early and late post-LT outcomes.
In 2018, nearly a quarter of patients (24.1%) on the waiting list were aged 65 y or older, nearly doubling the figure from a decade earlier. This trend has influenced the proportion of transplants conducted in patients older than 65 y, rising from 8% to 21% between 2002 and 2019,15 respectively. Several studies have reported favorable outcomes in elderly LT recipients, although only a small proportion of these procedures are performed in patients in their 70s or 80s.14,32-42 Even with selection bias favoring the transplanted cohort with severe obesity and advanced age in the low KPS category—those deemed the best candidates by initial evaluations (eyeball test)—their outcomes are significantly worse. Elderly obese patients in the low-performance group had 230% greater risk of EGL and 250% increased risk of 90-d mortality. Moreover, elderly patients with severe obesity and low-performance status had 56% and 59% increased risk of long-term allograft and patient survival, respectively. We believe the differences observed are likely attributable to a greater physiological reserve in individuals with intermediate or high functional status, irrespective of obesity severity. As a result, severely obese patients with better performance status may be more resilient to surgical stress and more capable of recovering from major postoperative complications compared with those with lower performance status. Among elderly patients (age older than 65 y) with severe obesity and low functional status, the added risk may be associated with sarcopenia or sarcopenic obesity, a condition commonly seen in this population.
This study has several limitations that should be acknowledged. One key limitation is its retrospective design using the UNOS data set. Additionally, the lack of detailed postoperative information restricts a more thorough analysis of issues related to graft loss, perioperative complications, and mortality. Patients with low KPS and severe obesity are less likely to be listed for transplant, and the selection criteria for these patients vary between centers, which could create an inherent selection bias. However, the strength of the study lies in its use of prospectively collected data from a large number of cases using UNOS.
In summary, although data on obesity and LT remain conflicting, our study shows that severe obesity in patients with a low-performance status before transplantation significantly increases the risk of poor perioperative and long-term outcomes. This effect is not seen in patients with higher performance scores, which underscores the importance of improving patients’ mobility and overall performance status before transplant. Additionally, the combination of severe obesity and advanced age (65 y or older) in low-performance status patients may have a compounded negative impact on posttransplant survival. Therefore, careful scrutiny during the patient selection phase is crucial. Implementing pre- and postrehabilitation therapy and optimizing nutrition protocols may help mitigate some of these risks and improve outcomes in the elderly, obese population with low-performance status undergoing LT.
Footnotes
The authors declare no funding or conflicts of interest.
A.C. and R.G. participated in conception and design. A.C., X.M., and R.G. participated in acquisition, analysis, and interpretation of data. A.C., M.G., A.A., M.B.S., X.M., S.D., and R.G. participated in article drafting and critical revision and gave final approval of the version to be published.
Contributor Information
Mackenzie Donoho, Email: mackenzie.donoho@uky.edu.
Siddharth Desai, Email: siddharth.desai@uky.edu.
Meera Gupta, Email: meera.gupta@duke.edu.
Alexandre Ancheta, Email: alexandre.ancheta@uky.edu.
Malay B. Shah, Email: malay.shah@uky.edu.
Xiaonan Mei, Email: xiaonan.mei@uky.edu.
Francesc Marti, Email: fmart3@email.uky.edu.
Roberto Gedaly, Email: rgeda2@uky.edu.
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