The Incidence of Sarcopenia is Low Among Israeli Liver Transplantation Patients and Associated with Lower Survival Estimates

Purpose: Sarcopenic patients have reduced musculoskeletal capacity and have poorer postsurgical outcomes. High rates of sarcopenia have been reported among Western liver transplantation candidates. The purpose of this study was to determine the incidence of sarcopenia in an Israeli liver transplant program and assess its effect on post-transplant outcomes. Methods: An observational retrospective study was performed using an updated database which included demographic and outcome measures of 100 consecutive liver transplant patients from deceased donors at the Hadassah Medical Center 2002-2012. Sarcopenia was assessed for those with available pre transplant abdominal CT studies. Psoas muscle measurements were obtained via CT and Lean Psoas Area (LPA) was calculated. Subjects were classified into sarcopenic according to an accepted convention of psoas LPA. Results: Thirty-four patients had CT studies appropriate for the sarcopenia analysis. Nine were females (26%) and 25 (74%) males. Mean transplant age was 52.6±11.3 and post-transplant follow up 6.3±3.7 years. By the Dolgin criteria only four males (12%) had sarcopenia. The productlimit survival estimate showed a statistically greater estimated survival for non-sarcopenia patients than for sarcopenia patients (log-rank test p=0.045), with a survival estimate at 98 months of 79% for non-sarcopenia patients and 25% for sarcopenia patients. Conclusions: Because Israeli sarcopenic liver transplantation patients have lower survival estimates along with inherent physical limitations compared to non-sarcopenic patients, it make sarcopenia an additional valuable variable for listing liver transplantation candidates, especially during the COVID-19 pandemic when donor supply to need mismatches have increased.

The presence of sarcopenia has been assessed by calculations derived from either DEXA scans, CT scans, bioelectric impedance measurements, or grip strength and walking speed [6]. What is sarcopenia and what is normal muscle mass is defined for each of the assessment methods, but values often differ between populations. The European Working Group on Sarcopenia in Older People (EWGSOP) has published criteria for sarcopenia for the European population [7]. Because of differences in their physique, different criteria have been published for the Asian population [8]. In some studies sarcopenia has been defined based on the measured value being one standard deviation below the average for the study population. All of this can make comparison of research results between clinical studies problematic.
Pre-transplant sarcopenia has been reported to exist in 50% of liver transplant patients in the US [9]. Similar rates have been reported in a Canadian study as well [6]. An Italian study reported an even higher sarcopenic rate of 76% among patients eligible for liver transplantation [5]. The Israel liver transplant program is of a much smaller scale than that of North American and Western The current report compares the sarcopenia incidence among Israeli adult liver transplant patients with those from major North American centers. The transplantation outcomes for the Israeli cohort are presented for those with and without sarcopenia.

Study Design and Population
The data of 100 successive liver transplant recipients in the and psychosocial scoring at transplant [10]. Also listed are the dates of clinic visits, comorbidity and mortality data including death date, rejection, biliary complications, nephrotic complications, infection, hyperkalemia and diabetes. All patients from this cohort who were older than 18 years at transplantation, underwent a first-time liver transplant from a deceased donor and had abdominal CT studies with sagittal reconstruction within the 25 months prior to transplant, were available for sarcopenia assessments. The rate of sarcopenia of the present cohort was compared to that of published American, [9] and Canadian [6] studies.

Sarcopenia measurement
Pre-transplant psoas muscle size (cross-sectional area, in mm2) and quality (density, Hounsfield units [HU]), which included both left and right psoas muscles, were measured at the L4 vertebral level superior plate. To minimize measurement bias, all measurements and calculations where done by the same investigator (YM).
The investigator was trained by a senior radiologist to perform calculations. The plane of the L4 vertebral level superior plate was determined on sagittal reconstruction. The axial image related to this level was used to determine the psoas area bilaterally.
In accordance with the method of Dolgin et al. [9], psoas muscle measurements were combined to create the following variables:

Sarcopenia cutoffs
The presence and absence of sarcopenia was defined for male subjects and female subjects separately according to the staturenormalized lean psoas area cutoff point of 1480.4 mm2 for males and 974.8mm2 for females [9]. These values were determined by Dolgin et al. [8] based on the Michigan Surgical Quality Collaborative database of 1,279 patients who underwent elective surgery at a single institution and had CT based LPA calculations [11]. The cut off point for sarcopenia was determined as one standard deviation below the average of lean psoas area.

Statistical analysis
Statistical analysis was performed using the Statistical Analysis System (SAS Institute Inc., Cary, North Carolina, USA, version 9.4).
Nominal data were assessed with the chi-square test and Fischer's exact test. Normally distributed interval data were compared across the groups, using 2-tail Student's t-test. Survival estimates for sarcropenic and non-sacropenic patients following transplant were done using the LIFETEST PROCEDURE (SAS). The product-limit survival estimate Figure 1 showed a statistically greater estimated survival for non-sarcopenia patients than for sarcopenia patients ( log-rank test p=0.045), with a survival estimate at 98 months of 79% for non-sarcopenia patients and 25% for sarcopenia patients.

Discussion
The presence of sarcopenia in itself affects the quality of life by lowering one's daily activity level [7]. Worldwide, its prevalence is 5-13% in those in the seventh decade of life and increases to 11-50% in those above 80 years old [12,13]. Adding the physical limitations imposed by sarcopenia to the liver transplantation patient, can compromise the quality of life achievements of the transplant.
The current study indicates that this co-morbidity is fortunately present in a minority of Israel liver transplant patients (12%) as opposed to the 50% incidences reported from US and Canadian studies using the same evaluation criteria for sarcopenia [9]. The study also found a statistically greater estimated survival for non

Conclusion
Given the possible mismatch between need and supply, this study indicates that sarcopenia might be a factor to consider when determining the list order in liver transplantation programs.
During the COVID-19 pandemic this mismatch is likely to become more prevalent.