Feb. 16, 2019
Sarcopenia is the progressive loss of skeletal muscle mass and a highly prevalent and impactful complication of cirrhosis. Individuals with this condition tend to experience poorer pre- and post-transplant outcomes than patients with preserved muscle mass. In liver transplant candidates, sarcopenia is associated with increased waitlist mortality and sepsis‐related death. Post-transplant outcomes associated with this condition include prolonged hospital and intensive care unit stay, increased risk of infection, and post‐liver transplant mortality.
Mayo researchers share details about studies addressing the role of sarcopenia and exercise in patients with end-stage liver disease awaiting liver transplant.
Defining sarcopenia in liver transplant candidates
Although multiple studies have reported an association between muscle mass and outcomes in liver transplant candidates, Mayo Clinic researchers recently noted that existing literature lacked a consistent definition of sarcopenia for this population. To address this issue, Mayo Clinic researchers conducted a retrospective and multicenter study that sought to determine the optimal definition of sarcopenia in patients with end-stage liver disease (ESLD) awaiting liver transplant. The results of that study were published in Liver Transplantation in 2017.
"Multiple studies have reported an association between muscle mass increased waitlist mortality in liver transplant candidates," explains Elizabeth J. Carey, M.D., a gastroenterologist and hepatologist specializing in liver transplantation at Mayo Clinic's campus in Arizona and the article's lead author. "But the definition of sarcopenia in this population varies from study to study."
Dr. Carey and colleagues sought to determine optimal cutoffs of skeletal muscle index (SMI) on computerized tomography imaging to define sarcopenia in patients with ESLD awaiting liver transplant.
This multicenter study included 396 patients from five transplant centers within the Fitness, Life Enhancement, and Exercise in Transplantation (FLEXIT) Consortium centers, which include the University of Alberta, Canada; Duke University, Durham, North Carolina; Mayo Clinic in Phoenix/Scottsdale, Arizona; University of Pittsburgh; Cleveland Clinic; and University of California, San Francisco.
Researchers measured the total cross-sectional area (cm2) of abdominal skeletal muscle at the third lumbar vertebra and then calculated the SMI, which normalizes muscle area to patient height. The primary outcome was waitlist mortality, defined as death on the waiting list or removal from the waiting list for reasons of clinical deterioration.
Mortality was 25 percent in men and 36 percent in women at a median of 8.8 months' follow-up. Patients who died had a lower SMI than those who survived (45.6 cm2/m2 versus 48.5 cm2/m2; P < 0.001), and the SMI was associated with waitlist mortality (hazard ratio, 0.95; P < 0.001).
Based on their findings, Mayo researchers propose that an SMI of less than 50 cm2/m2 for men and less than 39 cm2/m2 for women should be used to define sarcopenia in patients with ESLD awaiting liver transplant.
"These values best correlate with waitlist mortality, and we believe that they should be used for future research to help identify patients at risk of death on the waiting list," explains Dr. Carey. "Having a standard definition of sarcopenia will help us assess response to therapeutic interventions targeting sarcopenia in patients with cirrhosis. And by facilitating data comparisons across different studies, this uniform clinical criterion could also help guide the development of new therapies for sarcopenia in liver disease."
Perceptions about exercise among liver transplant patients and their caregivers
As noted earlier, impaired physical capacity and sarcopenia are gaining attention as key risk factors for death and morbidity before and after liver transplant. To address another facet of this issue, Mayo researchers recently conducted a study to assess patient and caregiver activity levels, perceptions about patients' willingness to exercise, and what kind of advice providers offer on this subject. The results of that study were published in Digestive Diseases and Sciences in 2018.
"Prior to this study, we didn't know much about patients' understanding about this important and complex topic," explains David M. Chascsa, M.D. Dr. Chascsa is a gastroenterologist and hepatologist specializing in liver transplantation at Mayo Clinic's campus in Arizona and the article's lead author. "Our goals were to address several unknowns," says Dr. Chascsa. "These included assessing whether patients and caregivers appreciate the degree to which impaired functional status impacts transplant outcomes, patients' willingness to exercise, their perceptions about exercise safety, and provider advice on this subject."
The study surveyed patients with ESLD listed for liver transplant presenting for routine outpatient visits and their caregivers and evaluated these participants over a three-month interval. Anonymous surveys addressed the importance and safety of exercise, type and duration of exercise performed, barriers, willingness to wear a monitoring device, and perceived provider recommendations. Study participants logged their responses using a Likert scale from 1 to 5. This study was conducted within the FLEXIT Consortium centers.
- In the 368 responses received, most participants perceived exercise as important.
- Most participants reported exercising three times a week for 30 minutes.
- A total of 80 percent endorsed walking (median response 2-agree; interquartile range [IQR] 1-2). Most did not jog, swim, cycle or strength train.
- Fatigue was reported by 70 percent of participants as the major barrier (median response 2; IQR 1-3).
- More than 90 percent of caregivers endorsed exercise as important (median response 1-strongly agree; IQR 1-2) and encouraged exercise (median response 2; IQR 1-2).
- More than 60 percent of patients (median response 2; IQR 1-3) and caregivers (median response 2; IQR 2-3) felt providers encouraged exercise.
"Overall, we found that patients and caregivers are receptive and willing to exercise to improve their fitness for liver transplantation," says Dr. Chascsa. "Future trials assessing the therapeutic efficacy of diet and exercise, with measurable performance endpoints, would provide insight into whether these interventions improve or sustain functional status in liver transplant candidates who say they are willing to make the needed effort. In addition, our results also suggest that ensuring caregiver engagement on this topic may enhance the efficacy of such interventions."
Future research on this topic
Moving forward with this vein of research, Mayo Clinic researchers are currently enrolling participants for two additional studies looking at exercise programs for patients on the liver transplant waitlist. One involves the use of a home exercise program and the other incorporates a more aggressive pulmonary rehabilitation program.
According to Kymberly D. Watt, M.D., a gastroenterologist and liver transplant specialist at Mayo Clinic's campus in Rochester, Minnesota, the clinical improvement observed in the participants involved in the studies so far appears notable, "but we need to await completion of the study." Given the effects of sarcopenia on post-transplant outcomes, the team is also looking at improvement of sarcopenia after transplant and the relationship to clinical outcomes longer term.
Dr. Watt says that Mayo Clinic researchers at all Mayo campuses are continuing efforts to improve the understanding of the pathogenesis of sarcopenia in this population. "We are moving closer to developing treatments that address the complex metabolic alterations in cirrhosis that contribute to muscle loss. We hope that this information will allow us to target specific changes in energy requirements, metabolic pathways, hormonal abnormalities and nutritional deficiencies," says Dr. Watt.
For more information
Carey EJ, et al. A multicenter study to define sarcopenia in patients with end-stage liver disease. Liver Transplantation. 2017;23:625.
Chascsa DM, et al. Patient and caregiver attitudes and practices of exercise in candidates listed for liver transplantation. Digestive Diseases and Science. 2018;63:3290.