Sarcopenia and mortality after liver transplantation

Abstract

Background: Surgeons frequently struggle to determine patient suitability for liver transplantation. Objective and comprehensive measures of overall burden of disease, such as sarcopenia, could inform clinicians and help avoid futile transplantations.

Study design: The cross-sectional area of the psoas muscle was measured on CT scans of 163 liver transplant recipients. After controlling for donor and recipient characteristics using Cox regression models, we described the relationship between psoas area and post-transplantation mortality.

Results: Psoas area correlated poorly with Model for End-Stage Liver Disease score and serum albumin. Cox regression revealed a strong association between psoas area and post-transplantation mortality (hazard ratio = 3.7/1,000 mm(2) decrease in psoas area; p < 0.0001). When stratified into quartiles based on psoas area (holding donor and recipient characteristics constant), 1-year survival ranged from 49.7% for the quartile with the smallest psoas area to 87.0% for the quartile with the largest. Survival at 3 years among these groups was 26.4% and 77.2%, respectively. The impact of psoas area on survival exceeded that of all other covariates in these models.

Conclusions: Central sarcopenia strongly correlates with mortality after liver transplantation. Such objective measures of patient frailty, such as sarcopenia, can inform clinical decision making and, potentially, allocation policy. Additional work is needed develop valid and clinically relevant measures of sarcopenia and frailty in liver transplantation.

Figure 1

The cross sectional area (mm²) of the psoas muscle stratified by age among otherwise healthy trauma patients (blue) and liver transplant recipients (red). Males are shown in figure 1a and females in 1b. Both male and female liver transplant recipients have significantly smaller psoas area compared to trauma patients. Psoas area decreases with age in both groups, though the slope of this decreased is larger in the trauma patients.

Figure 1

The cross sectional area (mm²) of the psoas muscle stratified by age among otherwise healthy trauma patients (blue) and liver transplant recipients (red). Males are shown in figure 1a and females in 1b. Both male and female liver transplant recipients have significantly smaller psoas area compared to trauma patients. Psoas area decreases with age in both groups, though the slope of this decreased is larger in the trauma patients.

Figure 2

The cross sectional area (mm²) of the psoas muscle stratified by preoperative serum albumin (g/dL). No clear relationship between TPA and pre-liver transplant serum albumin level was noted.

Figure 3

The cross sectional area (mm²) of the psoas muscle stratified by preoperative MELD score. A weak relationship is noted between preoperative MELD score and psoas muscle area, with a trend towards larger muscle areas among low MELD patients.

Figure 4

Effect of total psoas area (TPA) in post-liver transplant mortality, as quantified by the covariate adjusted hazard ratio (HR). The reference TPA (HR=1) is TPA=1.91 cm², which is the median TPA in our study population. The hazard ratio for a patient with TPA=1.42 was HR=1.88; i.e., a patient with TPA at the 25^th percentile has almost twice the post-transplant mortality rate of a patient at the median TPA, covariate-adjusted. For patients differing by 1000 mm² with respect to TPA, the patient with the higher TPA faces a post-transplant mortality rate equal to 25% (HR=0.27) of the patient with the lower TPA.

Figure 5

This figure shows the adjusted survival (one-year Figure 5a and three-year Figure 5b) of liver transplant recipients, stratified by quartiles of total psoas area (TPA). Holding all other covariates equal among the quartiles of TPA, the one year survival ranged from 49.7% among the group with the smallest TPA compared with 87.0% among the group with the largest TPA. (Figure 5a) Similarly, the three-year survival ranges from 26.4% among the group with the smallest TPA compared with 77.2% among the group with the largest TPA. (Figure 5b)

Figure 5

This figure shows the adjusted survival (one-year Figure 5a and three-year Figure 5b) of liver transplant recipients, stratified by quartiles of total psoas area (TPA). Holding all other covariates equal among the quartiles of TPA, the one year survival ranged from 49.7% among the group with the smallest TPA compared with 87.0% among the group with the largest TPA. (Figure 5a) Similarly, the three-year survival ranges from 26.4% among the group with the smallest TPA compared with 77.2% among the group with the largest TPA. (Figure 5b)

Figure 6

Box-whisker plot of the adjusted hazard ratio (HR) for total psoas area (TPA), recipient age, and donor age. The box includes the central 50% of the data, while the whiskers include the central 90%. The distribution is covariate-adjusted as a HR=1 is assigned for every adjustment covariate. Differences in TPA values across the study population produce very large differences in post-transplant mortality risk, even after factoring out the impact of the other covariates. When we compare TPA to other covariates (recipient and donor age), we note that TPA is associated with a more profound variation in the HR for mortality.