COMMENTARY

Physical Activity in Liver Transplantation: A Patient’sand Physicians’ Experience

Lara Beekman . Annalisa Berzigotti . Vanessa Banz

Received: July 27, 2018 / Published online: October 16, 2018� The Author(s) 2018

ABSTRACT

Liver transplantation has become a highlystandardized, acceptable option for selectedpatients with end-stage liver disease and/orhepatocellular carcinoma in the setting of cir-rhosis. Both conditions are associated with lossof skeletal muscle mass (sarcopenia) and physi-cal deconditioning. Both conditions result in adramatic decrease in the patients’ quality of life,negatively impacting on the pre- and post-transplant prognosis. In this context, awarenessof the advantages of physical activity in boththe pre- and post-transplant setting is key.However, the importance of regular, individu-alized and patient-adapted physical activity isstill understudied and underestimated. Thisarticle describes a three-sided perspective on theimportance of physical activity in the setting ofliver transplantation, including a patient’s,transplant surgeon’s and hepatologist’s point ofview.

Keywords: Exercise; Liver cirrhosis; Livertransplantation; Malnutrition; Physicalactivity; Reconditioning; Sarcopenia

INTRODUCTION

Liver transplantation (OLT) has become ahighly standardized, acceptable option forselected patients with severe complications ofliver disease. Reduction in skeletal muscle mass(sarcopenia) and function (physical decondi-tioning) are highly prevalent in patients on thewaiting list for liver transplantation. They resultin a dramatic decrease in the patients’ quality oflife, also negatively impacting the pre- and post-transplant prognosis. Awareness of the benefitsof physical activity in both the pre- (pre-condi-tioning) and post-transplant setting is increas-ing among the medical community. However,the importance of regular, individualized andpatient-adapted physical activity is still under-studied and underestimated, and it is certainlynot yet fully perceived as part of the therapy bymost of the patients. In this article, we discussthe importance of physical activity in the set-ting of liver transplantation by presenting athree-sided perspective including a patient’s,transplant surgeon’s and hepatologist’s point ofview.

Enhanced digital features To view enhanced digitalfeatures for this article go to https://doi.org/10.6084/m9.figshare.7093529.

L. Beekman � A. Berzigotti (&) � V. BanzDepartment for Visceral Surgery and Medicine, BernUniversity Hospital and University of Bern, Bern,Switzerlande-mail: annalisa.berzigotti@insel.ch

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https://doi.org/10.1007/s12325-018-0797-7

PATIENT’S EXPERIENCE

After having learned from my transplant sur-geon on October 14th, 2013, that my livertransplantation had been successful, I could nothave been a happier person. On the other hand,I was lying on the intensive care unit on strongdrugs and in a lot of pain, wondering how Iwould ever be able to sit up or even get out ofbed again.

Since I was a child, I have enjoyed a varietyof sports from figure skating to tap dancing andnow golf. Having lived through various difficulthealth issues (complications of portal hyper-tension due to portal vein thrombosis since Iwas 13 years old and liver adenomatosis withacute bleeding due to rupture at the age of 42,eventually leading to liver transplantation;placenta percreta at the age of 32), I have had toget up again and again after having beingknocked back numerous times. I thereforestrongly believe and have experienced thatkeeping active and fit helps people get throughillness and surgery more easily and successfully.

My first sports achievement after my livertransplant in 2013 was my daily staircase climbin the hospital, which was important to get mestrong enough to go home. I felt awful and itwas hard work, but I tried to make smallimprovements from 1 day to the next.

After returning home 10 days post-trans-plant, reality kicked in. I still had a long way togo to feel strong enough to lead an active familylife. The first weeks and months at home weretough because of the postoperative pain as wellas pain in numerous other muscles throughoutthe body and side effects from various medica-tions. Looking back, I now realize that I defi-nitely would have benefitted from earlyprofessional support on how to improve myphysical activity and how to go about these firststeps.

As an active working mother with threeteenagers, it is important that I contribute asmuch as possible towards counteracting thepossible side effects of immunosuppression (e.g.diabetes, high blood pressure, overweight, denovo tumors, etc.) [1]. Regular physical activityis one of the best ways to help avoid these

chronic diseases while at the same timeimproving physical and mental wellbeing andachieving a good quality of life [2]. According tothe current state of research, specialists agreethat regular exercise plays an extremely impor-tant role before and after organ transplantationin order to have a good quality of life withminimal restrictions and few chronic diseases[3]. Currently, many European liver transplantclinics inform their liver patients about theimportance and need for regular physicalactivity. However, in most cases a brief verbalencouragement or written information in abooklet is not enough to achieve a lasting effectin these patients. How they can be motivated tocarry out regular physical activity with a lastingeffect is still under-researched, and there arecurrently not enough scientifically substanti-ated foundations with matching long-termcontrols on this topic.

I wanted to know more about this andwanted to engage in the change needed toimprove the current situation. Two years post-transplant, I started my EMBA (Executive Mas-ter in Business Administration) training inhealth care economics and management anddecided to devote part of it to the topic ofphysical activity of liver transplant patients.

I carried out a qualitative study includinginterviews with transplant experts in order toprovide qualitative results and recommenda-tions for the education and monitoring ofphysical activity of liver transplant patients. Asa first step, the study included a comprehensiveliterature search and a search for best practiceinputs from other transplant clinics. In a nextstep, the topics and questions for the expertinterviews were validated by numerous Swissand international transplant specialists using anonline tool. The results of the study providedvaluable input regarding open issues, e.g., atwhat time, with which content, by which spe-cialists and with what kind of tools liverpatients should be instructed before and after aliver transplant for physical activity. In addi-tion, which barriers need to be considered andhow the physical activity and its effect on thepatients can be controlled and measured wereshown. This led to the design of a pilot project(Fig. 1) that is now entering a more detailed

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planning phase and hopefully will be imple-mented soon at our hospital, where I too wastransplanted.

In parallel, I started exercising on a regularbasis and began participating in the TransplantGames (Fig. 2). To take part in the World andEuropean Transplant Games was an importantgoal after my liver transplantation and helpedme get physically active and fit again. Not onlyare the Transplant Games a great motivation tokeep up regular physical activity but also a greatopportunity to meet and talk to other inspiringtransplant patients who have been throughsimilar experiences [4].

SURGEON’S EXPERIENCE

While most surgical techniques are becomingincreasingly minimally invasive and less trau-matic than they were a few decades ago,orthotopic liver transplantation (OLT) stillremains a major abdominal intervention, car-rying with it all the problems associated withsuch extensive surgery. There is evidence that

patients requiring elective intracavity surgeryprofit from so-called prehabilitation withincreased preoperative fitness levels [5]. The linkto the reduction in postoperative morbidity andmortality however remains weak. Nevertheless,a more recent randomized, blinded, controlledtrial evaluating the effects of individualizedprehabilitation in high-risk patients undergoingelective major abdominal surgery showed a 50%reduction in the number of patients sufferingfrom postoperative complications as well as asignificant reduction in the overall rate ofpostoperative complications [6].

With increasing numbers of patients on theliver transplant waiting lists and a worldwideshortage of donor organs, in many countriespatients wait long before receiving a new liver(median of about 12 months in Europe) [7].

In Switzerland, most patients will wait forover 12 months before finally getting a newliver. During this time, many will be in and outof the hospital because of complications associ-ated with end-stage liver disease, resulting in anexacerbation of their general deconditioning.

Fig. 1 Planned program of physical activity pre- and post-liver transplantation at our center

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Deconditioning combined with general frailty—as is commonly seen in this patient popula-tion—may have a detrimental effect not only inthe perioperative setting but also in the longterm. Indeed, the effect of preoperative frailtyon postoperative outcome is currently beingevaluated in many different post-surgical/post-interventional settings, and a recent study by Laiet al. was able to show that even in the setting ofa successful OLT, only two out of five patientswill eventually achieve robustness 1 year post-transplant [8]. This is all the more worryingwhen considering the fact that even the seem-ingly ‘‘better off’’ Child A patients primarily

receiving an OLT for hepatocellular carcinomasuffer from an equally relevant reduction ingeneral health status in the short and long termcompared with the obviously frail patients. Thisclearly shows the importance of implementing aroutine preoperative training program for all thepatients on the liver transplant waiting list ifcomplication rates and hospital length of stayare to be reduced in the short term and quality oflife and general robustness are to be increased inthe long term.

HEPATOLOGIST’S EXPERIENCE

The return to a normal life is the aim of medi-cine in general and of any organ transplanta-tion. As outlined by my colleague transplantsurgeon above, before undergoing OLT, mostpatients experience severe fatigue, protein-en-ergy malnutrition due to hypercatabolism andconsequently sarcopenia and deconditioning(decreased muscle strength, endurance andoxygen uptake) [9]. Importantly, even patientswho are obese before OLT suffer from theseconditions, presenting with so-called ‘‘sar-copenic obesity’’ [10]. Recovery of muscle massand function after transplantation is favored bythe normalization of liver function. However,without specific measures, this takes a longtime, during which patients are limited in theirdaily life. In addition, studies demonstrate thateven in the setting of successful transplanta-tion, deconditioning persists long term for notyet fully clarified reasons [11, 12]. Post-trans-plant, patients may go back to taking on asedentary life, something which by most maybe perceived as ‘‘normal.’’ Currently, lifeexpectancy of patients after OLT is excellent,with a 90% 1-year and over 70% 5-year survival.Five-year survival is expected to further improvein the near future, given that effective therapiesfor hepatitis C virus (representing the mainnegative prognostic factor after OLT) are nowavailable [7]. Long-term complications afterOLT are mostly related to cardiovascular eventsand cancer. Up to 58% of patients develop car-diovascular risk factors or metabolic syndrome(elevated arterial blood pressure, diabetes,atherogenic dyslipidemia and obesity) [13],

Fig. 2 Mrs. Beekman silver medal in long jump at the2018 European Transplant Games in Cagliari, Italy

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which are in part due to the use of immuno-suppressant medication such as calcineurininhibitors and/or mTOR inhibitors [14]. Notsurprisingly, and similarly to what is observedin the general population, the presence of obe-sity and a metabolic syndrome increases the riskof stroke, myocardial infarction as well aschronic renal failure and de novo malignanciesin OLT patients [15]. Modifying these risk fac-tors thus favorably impacts the long-termprognosis of patients post-OLT. Importantly,exercise alone proved effective in reducing theonset of metabolic syndrome after OLT in twostudies [13, 16]. In addition, physical activitydramatically improves quality of life in thissetting, with a strong correlation between levelof fitness/physical activity and quality of life[16–20]. Nonetheless, only one quarter ofpatients are physically active after transplanta-tion [16]. Large randomized controlled studiesin this field are lacking. However, in view of theexisting evidence, the European Association forthe Study of the Liver (EASL) recommends thatphysical activity should be proposed as part ofthe therapeutic regimen after OLT [21].

DISCUSSION AND NEXT STEPS

Improving physical activity for patients under-going OLT is a challenge at many differentlevels. It is a challenge for the medical com-munity since it requires an interdisciplinaryteam effort implying the integration of newspecialists (such as sports medicine specialists)in the existing liver transplantation process aswell as intensified communication betweenmedical specialists and family physicians. It is achallenge for the health system as it impliesusing resources to focus on prevention and theorganization of a network between hospitalsand private, non-hospital-based facilities. It is,of course, also a challenge for the patients, towhom we need to listen carefully in order toadapt physical activity programs. This might beparticularly true for women, who due to maritaland parental duties might be disadvantaged inundertaking physical activities, something veryrelevant in certain cultures. Patients need to besupported and empowered (barriers and

motivation) at the same time in order for themto be able to care for their physical activity inthe long term. New physical activity programsalso need to adhere to sustainability and safetyprinciples, with a continuous evaluation ofclinical and quality of life end points. Severalquestions still need to be clarified by futureresearch: when should patients start theirtraining? Which kind of training is best? Whatare the best end points to use in trials con-cerning physical activity in livertransplantation?

Our team in Bern is convinced that all thesefinancial, organizational and cultural chal-lenges are worth embracing and research aimedat answering the above-mentioned questions isessential and worthwhile. Our team is workingon setting up a program integrating patient-adapted physical activity into the liver trans-plant program routine. As Lara’s example bril-liantly shows, physical activity is a powerfultool to help patients prepare for liver trans-plantation and return back to a normal, healthyand fulfilling life post-transplant.

ACKNOWLEDGEMENTS

Funding. No funding or sponsorship wasreceived for this study or publication of thisarticle.

Authorship. All named authors meet theInternational Committee of Medical JournalEditors (ICMJE) criteria for authorship for thisarticle, take responsibility for the integrity ofthe work as a whole and have given theirapproval for this version to be published.

Disclosures. Lara Beekman, AnnalisaBerzigotti and Vanessa Banz have nothing todisclose.

Compliance with Ethics Guidelines. In-formed consent was obtained from all individ-uals for whom identifying information isincluded in this article.

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Open Access. This article is distributedunder the terms of the Creative CommonsAttribution-NonCommercial 4.0 InternationalLicense (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommer-cial use, distribution, and reproduction in anymedium, provided you give appropriate creditto the original author(s) and the source, providea link to the Creative Commons license, andindicate if changes were made.

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