Understanding Current Limitations to Exercise Interventions After Liver Transplantation : Transplantation

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Understanding Current Limitations to Exercise Interventions After Liver Transplantation

Thuluvath, Avesh J. MD, MS1,2; Lai, Jennifer C. MD, MBA3

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Transplantation 107(1):p e1-e2, January 2023. | DOI: 10.1097/TP.0000000000004314
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Frailty is prevalent in patients with cirrhosis and is associated with poor health outcomes both before and after liver transplantation. Although recovery of hepatic synthetic function and resolution of portal hypertensive complications are rapid and complete after transplantation, improvement in physical deconditioning often lags behind. Studies have demonstrated that frailty and sarcopenia worsen in the 6–12 mo following liver transplantation and only modestly improve thereafter. Persistent physical deconditioning is detrimental to transplant recipients’ recovery from a major surgery that depleted their physiologic reserve. Therefore, targeted interventions to improve frailty are critical to optimizing transplant care moving forward.

In this issue of Transplantation, De Smet et al1 present a comprehensive systematic review and meta-analysis on exercise interventions designed to improve physical fitness and health-related quality of life (HRQOL) after liver transplantation. This meta-analysis, including data from 8 randomized controlled trials (RCTs), demonstrated that exercise interventions (consisting of aerobic and resistance training) are safe in patients following liver transplantation, with no reported exercise-related adverse events in supervised or unsupervised interventions. Notably, the authors found a trend towards increased cardiopulmonary fitness (measured by VO2 peak and 6-min walking distance) and lower body muscular strength following exercise interventions. The meta-analysis also revealed significant improvement in patient-reported physical function, demonstrating that HRQOL can be optimized with targeted exercise regimens.

In summarizing the current literature on exercise interventions after liver transplantation, this systematic review offers us the opportunity to highlight 3 major considerations for the development and successful execution of posttransplantation exercise programs. The first consideration is the timing of exercise initiation. It is noteworthy that all of the interventions studied were initiated after transplant recipients were transferred out of the intensive care unit (ICU). Although patients often transition to general surgical floors within 48–72 h of liver transplantation, patients with complicated postoperative courses remain in the ICU for prolonged periods of time, during which they are particularly vulnerable to accelerated muscle wasting. Liver transplant recipients are also at an increased risk of rehospitalizations after their index transplant admission, with nearly half of transplant recipients experiencing a serious complication requiring an invasive procedure in the first year after transplantation.2 Although exercise is likely to improve outcomes at any stage of posttransplant recovery, exercise interventions will need to be flexible enough to adapt to a patient’s changing physical capabilities after significant clinical events.

Second, the outcomes of these studies were quite heterogeneous and ranged from quantitative morphomics (eg, skeletal muscle mass) and isolated muscle function (eg, knee extensor muscle strength) to cardiopulmonary function (eg, 6-min walking distance), metabolic parameters (eg, waist circumference, blood pressure), and HRQOL. Although these outcomes are all important, the field would benefit from consensus endpoints that would allow future interventions to be compared head-to-head and enable the identification of the most suitable exercise interventions for specific patients. For example, a patient with sarcopenia might benefit greatest from an intervention that improved muscle mass but may not have improved metabolic parameters. Another patient who has adequate muscle mass but is at high risk for posttransplant metabolic syndrome may benefit greatest from an intervention that reduces waist circumference.

Last, adherence to posttransplant exercise programs was highly variable, ranging from 37% to 82% in the unsupervised interventions.3-5 Supervised interventions improved adherence to 94%–100% by requiring patients to attend scheduled, in-person training sessions.6,7 Yet supervised physical therapy, which must be continued long term to improve and maintain physical fitness, is not logistically or financially feasible for the majority of patients who live far from transplant centers or lack availability and resources for travel. Strategies to improve adherence, such as providing home exercise equipment, frequent exercise reminders, and motivational interviewing, have had limited success in RCTs. Levying technology to better engage patients in exercise, however, has led to promising results, with studies using personal activity monitors and smartphone applications resulting in significant improvement in frailty and total activity levels.8,9 Other novel approaches to increasing patient engagement include gamification features on smartphone applications, online message boards that create a sense of community, and the potential utilization of artificial intelligence to monitor physical activity and thus accurately assess adherence remotely.10

De Smet et al’s systematic review of postliver transplant exercise interventions reveals that initiating early exercise programs in liver transplant recipients is safe and improves patient-reported physical function. However, it demonstrates the need for further well-designed RCTs and consensus outcome measures that will allow studies to be compared directly. Moreover, this article underscores the significant barriers to improving physical fitness posttransplant, most notably poor adherence to prescribed exercise programs. Future studies focused on improving patient engagement and adherence to home exercise regimens will be critical to improving physical fitness and thus posttransplant outcomes.


1. De Smet S, O’Donoghue K, Lormans M, et al. Does exercise training improve physical fitness and health in adult liver transplant recipients? A systematic review and meta-analysis. Transplantation. 2023;107:e11–e26.
2. Muller X, Marcon F, Sapisochin G, et al. defining benchmarks in liver transplantation: a multicenter outcome analysis determining best achievable results. Ann Surg. 2018;267:419–425.
3. Krasnoff JB, Vintro AQ, Ascher NL, et al. A randomized trial of exercise and dietary counseling after liver transplantation. Am J Transplant. 2006;6:1896–1905.
4. Hickman IJ, Hannigan AK, Johnston HE, et al. Telehealth-delivered, cardioprotective diet and exercise program for liver transplant recipients: a randomized feasibility study. Transplant Direct. 2021;7:e667.
5. Mandel D. Comparison of targeted lower extremity strengthening and usual care progressive ambulation in subjects post-liver transplant: a randomized controlled trial (Chapter 3). Available at https://scholarship.miami.edu/esploro/outputs/doctoral/Comparison-of-Targeted-Lower-Extremity-Strengthening/991031447535402976#file-0. Accessed June 29, 2022.
6. Moya-Nájera D, Moya-Herraiz Á, Compte-Torrero L, et al. Combined resistance and endurance training at a moderate-to-high intensity improves physical condition and quality of life in liver transplant patients. Liver Transpl. 2017;23:1273–1281.
7. Garcia AM, Veneroso CE, Soares DD, et al. Effect of a physical exercise program on the functional capacity of liver transplant patients. Transplant Proc. 2014;46:1807–1808.
8. Duarte-Rojo A, Bloomer PM, Rogers RJ, et al. Introducing EL-FIT (Exercise and Liver FITness): a smartphone app to prehabilitate and monitor liver transplant candidates. Liver Transpl. 2021;27:502–512.
9. Thuluvath AJ, Belfanti K, Morrissey S, et al. Home-based liver frailty intervention (lift) in liver transplant candidates: a pilot study. In: American Transplant Congress 2021. 2021. Available at https://atcmeetingabstracts.com/abstract/home-based-liver-frailty-intervention-lift-in-liver-transplant-candidates-a-pilot-study/. Accessed June 19, 2022.
10. Duarte-Rojo A, Budhraja V, Veldt BJ, et al. Interleukin-28B and fibrosing cholestatic hepatitis in posttransplant hepatitis C: a case-control study and literature review. Liver Transpl. 2013;19:1311–1317.
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