ORCID: Wesley D. Jetten,
These authors have contributed equally to this work
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Prehabilitation improves surgical outcomes in patients undergoing surgery. However, patients preparing for orthotopic liver transplantation (OLT) are physically “frail” and suffer from comorbidities that generally hamper physical activity. This systematic review aims to evaluate the physical effects, safety and feasibility of prehabilitation in OLT candidates. Relevant articles were searched, in Embase, Web of Science, Cochrane, Medline and Google Scholar, to December 2021. Studies reporting on specified preoperative exercise programs, including adult OLT candidates with end-stage liver disease, with a model for end-stage liver disease (MELD) score ≥12 or Child-Pugh classification B/C, were included. This resulted in 563 potentially eligible studies, out of which eight were selected for inclusion, consisting of 1,094 patients (male sex 68%; mean age 51–61 years; mean MELD score 12-21). Six of the included studies were classified as low-quality by the GRADE system, and three studies had high risk for ineffectiveness of the training program according to the i-CONTENT tool. Significant improvement was observed in VO2 peak, 6-minute walking distance, hand grip strength, liver frailty index and quality of life. Feasibility ranged from an adherence of 38%–90% in unsupervised-to >94% in supervised programs. No serious adverse events were reported. In conclusion, prehabilitation in patients awaiting OLT appears to improve aerobic capacity, and seems feasible and safe. However, larger clinical trials are required to accurately examine the preoperative and postoperative effects of prehabilitation in this specific patient population.
Poor physical fitness and functional status compromise postoperative functional recovery and lead to adverse postoperative outcomes, including complications, prolonged length of in-hospital stay, and mortality (
In current practice, patients who undergo (major) abdominal surgery are postoperatively supported by physical therapists and dieticians as part of the Enhanced Recovery After Surgery (ERAS®) program to accelerate postoperative recovery by enhancing perioperative health and reducing the impact of hospitalization and surgical stress (
Previous studies showed that prehabilitation programs are feasible, safe, and effective in patients scheduled for major abdominal surgery (
Moreover, previous research in OLT candidates predicted a higher survival after OLT in patients with a higher anaerobic threshold (a submaximal exercise parameter of cardiorespiratory reserve) (
The primary objective of this systematic review is to evaluate the observed effects of preoperative training on physical and functional capacity, and to evaluate the effect of prehabilitation on postoperative surgical outcomes after OLT. The secondary objective is to determine the feasibility and safety of prehabilitation programs in patients awaiting OLT. In addition to the primary and secondary objectives, we aim to provide an overview of the studied prehabilitation programs, including their content and potential for success (
This systematic review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement (
The search strategy was developed in collaboration with a clinical librarian and information specialist and was executed in Embase, Web of Science, Cochrane, Medline (PubMed) and Google Scholar. Free text words and MeSH terms related to prehabilitation and liver transplantation were used. Reference lists of relevant review articles and current treatment guidelines were screened for additional eligible articles. All studies published before 21 December 2021 were included for screening by title and abstract. The full literature database search strategy is described in
All peer-reviewed randomized, controlled, and cohort studies reporting a specified preoperative exercise program for adult (age ≥18 years) patients actively listed for OLT or with end-stage liver disease (ESLD). To assess ESLD, the model for end-stage liver disease (MELD) score, a disease severity scoring system used to improve organ allocation for patients on the liver transplantation waiting list, and the Child-Pugh classification were used. Studies that assessed patients with a laboratory or exception MELD score ≥12 or a Child-Pugh classification B or C were included. Animal studies, case-reports, systematic reviews, conference abstracts, duplicates and studies containing paediatric patients were excluded.
Quality assessment of included studies was executed by using the principles of the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) (
The primary outcome was defined as the observed effects of preoperative training programs on physical and functional capacity and surgical outcome. Physical and functional capacity was assessed by comparing outcomes such as pre- and post-training oxygen consumption at peak exercise (VO2-peak), 6-minute walking distance (6MWD), hand grip strength, and quality of life (QoL). Surgical outcome was assessed by comparing data on post-OLT complications, length of in-hospital stay, length of intensive care unit (ICU) stay, and mortality.
Secondary outcomes were safety and feasibility of study- and training programs. The safety of training programs was assessed by comparing the occurrence and types of serious adverse outcomes during the training. The feasibility of studies was assessed by comparing patients identified as eligible for inclusion with the total number of included patients. The feasibility of training programs was assessed by an evaluation of the adherence to the training programs during the waiting period prior to OLT.
Following the screening and selection of included studies, data was extracted by two independent authors (WJ, RH). Patient characteristics extracted included age; sex; body mass index (BMI); (lab and/or exception) MELD score; Child-Pugh classification and comorbidities, including diabetes mellitus, cardiac disease, pulmonary disease, ascites, gastroesophageal varices, and hepatic encephalopathy. Data regarding primary and secondary outcomes were extracted and tabulated. In addition, rationales, designs of the training programs, data on duration, frequency of training and exercises, training intensity and context, supervision of the training programs, and their potential for success were tabulated to provide a detailed overview of the prehabilitation programs. Normally distributed variables are presented as means with standard deviation (SD) and skewed variables as medians with interquartile range (IQR).
The search of aforementioned databases provided a total of 892 articles possible for inclusion. After removing duplicates, 563 articles remained for screening by title and abstract. Of these, 510 were excluded based on titles and abstracts. The full-texts of the remaining 53 articles were assessed for eligibility and reviewed in detail, whereafter 47 papers were excluded and six papers were included (
Flow diagram of the article selection procedure based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.
Designs of included studies and patient demographics.
Author | Limongi ( |
Debette-Gratien ( |
Al-Judaibi ( |
Wallen ( |
---|---|---|---|---|
Year | 2014 | 2015 | 2019 | 2019 |
Study Design | Randomized controlled trial | Prospective cohort study | Retrospective cohort study | Randomized controlled trial |
Study quality |
Low | Low | Low | Moderate |
Population (n) | ||||
Training group | 5 | 13 | 258 | 11 |
Control group | 12 | NA | 200 | 10 |
Demographics | ||||
Age, years | 49 (40–60) |
|||
Training group | 53.41 (8.42) | 51 (12) | 53.4 (9.6) | NR |
Control group | 56.2 (3.96) | NA | 56.5 (10.7) | NR |
Sex, male, % | 81% | |||
Training group | 92% | 77% | 26% | NR |
Control group | 60% | NA | 68% | NR |
BMI, kg/m2 | ||||
Training group | 31 (7.4) | NR | NR | NR |
Control group | 28 (3.8) | NA | NR | NR |
MELD-score | 13.3 ( |
|||
Training group | 17.58 (4.46) | 13 (6) | 18 (6–40) |
NR |
Control group | 17 (3.93) | NA | 21 (4–40) |
NR |
Child Pugh-score | 63% |
|||
Training group | NR | B7 (3) | NR | NR |
Control group | NR | NA | NR | NR |
Comorbidities, n(%) | ||||
Diabetes Mellitus | 33% | |||
Training group | 3 (60%) | NR | 90 (35.9%) | NR |
Control group | 3 (25%) | NA | 43 (21.5%) | NR |
Cardiac disease | 0% | |||
Training group | 1 (20%) | 0 (0%) | 27 (10.8%) | NR |
Control group | 0 (0%) | NA | 2 (1%) | NR |
Pulmonary disease | ||||
Training group | 1 (20%) | NR | NR | NR |
Control group | 2 (17%) | NA | NR | NR |
Ascites | ||||
Training group | 2 (40%) | 2 (15%) | NR | NR |
Control group | 8 (67%) | NA | NR | NR |
Gastroesophageal Varices | 81% | |||
Training group | NR | NR | NR | NR |
Control group | NR | NA | NR | NR |
Hepatic encephalopathy | ||||
Training group | NR | NR | NR | NR |
Control group | NR | NA | NR | NR |
Author | Williams ( |
Morkane ( |
Chen ( |
Lin ( |
---|---|---|---|---|
Year | 2019 | 2019 | 2020 | 2021 |
Study Design | Prospective cohort study | Prospective cohort study | Randomized controlled trial | Ambispective cohort study |
Study quality |
Low | Low | Low | Moderate |
Population (n) | ||||
Training group | 18 | 16 | 9 | 517 |
Control group | NA | 17 | 8 | NA |
Demographics | ||||
Age, years | ||||
Training group | 55 (44-63) |
55.6 (7.8) | 55 ( |
61 (53-66) |
Control group | NA | 55.6 (7.8) | 54 ( |
NA |
Sex, male, % | ||||
Training group | 50% | 88% | 56% | 59% |
Control group | NA | 82% | 75% | NA |
BMI | ||||
Training group | 25.4 (21-45) |
30.9 (5.6) | 31 ( |
30 ( |
Control group | NA | 27 (4.7) | 29 ( |
NA |
MELD-score | ||||
Training group | 13 (12-26)2 | 13.7 (4.6) | 16 ( |
12 ( |
Control group | NA | 13.2 (3.7) | 19 ( |
NA |
Child Pugh-score | ||||
Training group | NR | NR | 9 (100%) |
NR |
Control group | NR | NR | 8 (100%) |
NR |
Comorbidities, n (%) | ||||
Diabetes Mellitus | ||||
Training group | 1 (5.6%) | NR | 4 (45%) | 227 (44%) |
Control group | NA | NR | 1 (13%) | NA |
Cardiac disease | ||||
Training group | 1 (5.6%) | NR | NR | 57 (11%) |
Control group | NA | NR | NR | NA |
Pulmonary disease | ||||
Training group | NR | NR | NR | 36 (7%) |
Control group | NR | NR | NR | NA |
Ascites | ||||
Training group | 6 (33%) | NR | 7 (78%) | 352 (69%) |
Control group | NA | NR | 6 (75%) | NA |
Gastroesophageal Varices | ||||
Training group | NR | NR | 5 (56%) | 340 (67%) |
Control group | NR | NR | 7 (88%) | NA |
Hepatic encephalopathy | ||||
Training group | 6 (33.3%) | NR | 9 (100%) | 271 (53%) |
Control group | NA | NR | 8 (100%) | NA |
Quality assessment according to the GRADE system for quality assessment of clinical studies (
Data presented as median (IQR).
Data presented as median (range).
no of patients with Child Pugh B or C.
Data are presented as mean (SD) unless stated otherwise.
BMI, body mass index; MELD, model for end-stage liver disease score; NA, not applicable; NR, not reported.
According to the GRADE system (
Details of included training programs.
Author | Limongi ( |
Debette-Gratien ( |
Al-Judaibi ( |
Wallen ( |
---|---|---|---|---|
Exclusion criteria | Age <18; Acute liver failure | No prevention of esophageal bleeding (β-blockers or varices ligation); Ventricular ejection fraction <45%; Arrhythmia/cardiac decompensation during excercise | None | Previous LT; Listed for other organ transplantation; Current smoking; Adverse event during CPET; Uncontrolled diabetes; Orthopedic/neurological limitation to exercise |
Training details | ||||
Training group | Physical training | Physical training | Physical training and nutritional support | Physical training |
Control group | No exercises. | NA | Before implementation of training program. | No information regarding exercise training or physical activity provided. |
Supervision training | Unsupervised training at home by manual. | Supervised in-hospital gym. | Supervised in hospital gym or unsupervised at home with twice/thrice weekly supervision through phone calls | Supervised in hospital gym and unsupervised at home. |
Duration training, weeks | 12 | 12 | Until suitable for transplantation | 8 |
Mean duration not reported | ||||
Frequency training | Daily | Twice weekly | 1-5 times weekly | Thrice weekly |
Type of training | 1. Cough and breathing exercises | 1. Aerobic training (cycle ergometer) | 1. Aerobic training (cycle ergometer) | 1. Aerobic training (cycle ergometer or walking) |
2. Isometric force exercises. | 2. Muscle strength exercise (Press body building type) | 2. Resistance strength exercise | 2. Resistance strength exercise (circuit-based with weights) | |
3. Education regarding activity. | ||||
Risk of ineffectiveness of training program |
High | Low | High | Low |
Author | Williams ( |
Morkane ( |
Chen ( |
Lin ( |
---|---|---|---|---|
Exclusion criteria | Cardiovascular instability; CVA; ≥ grade 2 hepatic encephalopathy | Noncirrhotic liver disease; oncological diagnosis; contraindication for exercise | Large gastrointestinal varices without β-blocker use; HCC; hepatic encephalopathy; hydrothorax; pulmonary vascular complications of portal hypertension; cardiorespiratory contraindications for exercise | No exclusion criteria |
Training details | ||||
Training group | Physical training | Physical training | Physical training and nutritional support | Exercise prescription and one dietary consultation |
Control group | NA | CPET at 0, 6 and 12 weeks, no exercise program | Nutritional support only | NA |
Supervision training | Unsupervised at home | Supervised in hospital gym | Unsupervised training at home | Unsupervised home-based exercise workouts |
Once weekly supervision through phone calls | Weekly supervised counseling and daily motivational phone calls | Rarely: supervised home-based or outpatient physical therapy | ||
Once monthly phone follow-up and appointment after 90 - 120 days | ||||
Duration training (weeks) | 12 | 6 | 12 | Until LT |
Frequency training | Twice weekly, 20 minutes exercise | Thrice weekly, 40 minutes. | Recommendation of 5 times weekly, 30 minutes. | Recommendation of 5 times weekly, 30 minutes |
Thrice daily, 10 minutes walking. | ||||
Type of training | 1. Functional resistance exercises (video guide) | Aerobic training (cycle ergometer) | Walking training by increasing daily step-goal (Fitbit). | Home exercise program: |
2. Aerobic exercises (video guide) | 1. force: weights / resistance bands | |||
3. Walking program (daily step targets) | 2. aerobic: treadmills, elliptical or stationary bikes | |||
Risk of ineffectiveness of training program |
Low | Low | High | Low |
Risk of ineffectiveness of training program according to the i-CONTENT tool for assessing therapeutic quality of exercise programs employed in clinical trials (
LT, liver transplantation; CPET, cardiopulmonary exercise test; NA, not applicable.
Eight studies investigating a total of 1,094 patients (median (IQR): 20 (17–139)) were included. A total of three randomized controlled trials (RCTs) (
The majority of patients were male (68%). The mean or median age of the patients included in the training programs and control groups ranged from 51 to 61 and 54 to 56, respectively. In the studies reporting BMI, mean BMI in the training groups was ranging from 25.4 to 31 (
The primary outcomes reported on in the included studies varied and included alterations in spirometry results (
Three of six studies that implemented unsupervised home-based training programs provided once-to-thrice weekly telephone contact for supervision or motivational support (
Physical training programs mainly consisted of aerobic training by cycle ergometer or walking programs (
All the studies examining the physical effects of aerobic training reported some significant improvement in aerobic capacity (
Physical effects of training in patients awaiting orthotopic liver transplantation.
Author | Aerobic capacity | Functional capacity | |||||||
---|---|---|---|---|---|---|---|---|---|
VO2 peak (ml/kg/min) | 6MWD (m) | Handgrip strength (kg) | |||||||
Before training | After training |
|
Before training | After training |
|
Before training | After training |
|
|
Debette-Gratien ( |
21.5 (5.9) | 23.2 (5.9) |
|
481 (69) | 521 (64) |
|
30 ( |
37 ( |
|
Wallen ( |
|||||||||
Training/control |
NR | NR | NR | +103.8 (81.4) |
|
NR | +6.3 (8.5) | 0.24 | |
Morkane ( |
|||||||||
Training | 16.2 (3.4) | 18.5 (4.6) |
|
NR | NR | 26.4 (7.5) | 29.4 (6.4) |
|
|
Control | 19.0 (6.1) | 17.1 (6.0) |
|
NR | NR | 29.1 (10.7) | 30.5 ( |
0.8 | |
Chen ( |
|||||||||
Training | 18 (7) | 17 (6) | 0.42 | 423 (60) | 482 (87) |
|
NR | NR | |
Control | 18 (6) | 15 (7) | 0.08 | 418 (59) | 327 (166) | 0.21 | NR | NR | |
|
|
||||||||
Lin ( |
Before training | After training |
|
Before training | After training |
|
Before training | After training |
|
Training (all patients) | 1.0 (0.8–1.2) |
|
0.20 | 326 (244–390) |
|
0.13 | 3.8 (3.3–4.5) |
|
|
Training (full adherence group) |
1.0 (0.8–1.2) |
|
0.32 | 326 (244–390) |
|
0.07 | 3.8 (3.3–4.5) |
|
|
Control | NR | NR | NR | NR | NR | NR | NR | NR | NR |
|
|
||||||||
Before training | After 12 weeks |
|
Before training | After 6 weeks |
|
||||
Williams ( |
NR | NR | NR | 260 (70–1020) | 470 (190–880) |
|
9.5 ( |
11.5 ( |
|
|
|
||||||||
Before training | After training |
p-value | Before training | After training |
p-value | ||||
Limongi ( |
|||||||||
Training | 82.8 (13.1) | 87 (7.9) | NR | 76 (17) | 82 (14.5) | NR | NR | NR | |
Control | 84.3 (12.2) | 87 (19.2) | NR | 84.3 (12.8) | 85.4 (15.2) | NR | NR | NR | |
Al-Judaibi ( |
NR | NR | NR | NR | NR | NR |
The control group did not receive any training.
Only between-group changes (intervention vs. control) were reported in the study.
This study did not mention after-training outcomes as absolute numbers, but as delta points (F).
Full adherence: study patients who completed >80% of workout sessions.
Data are presented as mean (SD) or median (IQR).
VO2 peak, oxygen consumption at peak exercise; 6MWD, 6-minute walking distance; F, delta points; GST, gait speed test; LFI, liver frailty index; FVC, forced vital capacity; FEV1 = forced expiratory volume in one second; ISWT, incremental shuttle walk test; SPPBT, short physical performance battery test; NR, not reported.
Four studies examined QoL before and after the training program while awaiting OLT (
Effect of training on quality of life in patients awaiting orthotopic liver transplantation.
Author | Tool | Quality of life | ||
---|---|---|---|---|
Before training | After training |
|
||
Debette-Gratien ( |
SF-36 | 36 (4) | 39 (3) | 0.46 |
Wallen ( |
||||
Training/control |
HR-QoL | NR | −0.3 (−1.3,0.8) | 0.67 |
Williams ( |
EQ-VAS | NR | “Improvement of 18%” |
|
EQ-5D | NR | Improvement in: 44% - Mobility | ||
No-problems reported | 56% - Pain/discomfort | |||
HADS | 10 (1–26) | 7 (0–22) | 0.13 | |
Chen ( |
||||
Training | SIP | 11.2 (7.3) | 7 (6.4) | 0.10 |
Control |
SIP | 11.5 (13) | 15.7 (17.3) | 0.07 |
Limongi ( |
NR | |||
Al-Judaibi ( |
NR | |||
Morkane ( |
NR | |||
Lin ( |
NR |
The control group did not receive any training.
Only between-group changes (intervention vs. control) were reported in the study.
Data are presented as mean (SD) or median (IQR).
SF-36, Short Form 36; HR-QoL, health related quality of life; EQ-VAS, EuroQol visual analogue scale; EQ-5D, european quality of life five dimensions; HADS, hospital anxiety and depression score; SIP, sickness impact profile; NR, not reported.
Two studies (
Effect of training on postoperative surgical outcome after orthotopic liver transplantation.
Author | Length of hospital stay (days) |
|
Length of ICU stay (days) |
|
90-day readmission rate |
|
---|---|---|---|---|---|---|
Williams ( |
10 (5–41) | 4 (1) | NR | |||
Al-Judaibi ( |
||||||
Training | 14 (3–150) | 0.69 | NR | 17% | 0.58 | |
Control | 17 (5–161) | NR | 20% | |||
Morkane ( |
||||||
Training | 13 (7–19) |
|
2 (4) | 0.77 | NR | |
Control | 30 (17–43) | 4 (5.5) | NR | |||
Debette-Gratien ( |
NR | NR | NR | |||
Limongi ( |
NR | NR | NR | |||
Wallen ( |
NR | NR | NR | |||
Chen ( |
NR | NR | NR | |||
Lin ( |
NR | NR | NR |
Data are presented as mean (SD), median (IQR) or n (%).
ICU, intensive care unit; NR, not reported.
Three studies reported on the participants identified for possible inclusion and the reasons for exclusion. Wallen et al. identified 38 patients, of whom 15 declined to participate; one patient was transplanted before the start of the training program, and another was delisted before commencement, leaving 21 (55%) suitable for inclusion (
Outcomes regarding safety, feasibility, and adherence to the training programs are displayed in
Feasibility and safety of prehabilitation in patients awaiting orthotopic liver transplantation.
Author | Feasibility/Adherence to the program | Safety and adverse events | No. patients lost to follow up intervention group |
---|---|---|---|
Debette-Gratien ( |
NR | 1 – worsening hepatorenal syndrome | 2 – moved to another region |
No cardiovascular events | 2 –transplanted before 12 weeks | ||
No cirrhotic decompensation | 1 – deterioration of clinical condition | ||
No variceal bleeding or ascites) | |||
Wallen ( |
95% adherence to supervised exercise training | 1 – adverse event (knee injury) | 5 – transplanted before 8 weeks |
75% adherence to unsupervised exercise training | No serious adverse events | 1 – delisted and noncompliant | |
No variceal bleeding or hepatic encephalopathy | |||
Williams ( |
82% adherence to step-targets | No adverse events | 1 – non-study related trauma |
90% adherence to twice weekly exercises | |||
Morkane ( |
94% of total exercise sessions were completed | No adverse events | 1 – transplanted before 12 weeks |
No worsening cirrhotic decompensation | |||
Chen ( |
NR | NR | 1 – other surgery |
1 – transplanted before 12 weeks | |||
1 – lost to follow-up | |||
Lin ( |
Adherence to minimally 1 follow up: | NR | 24 – failed to visit follow up sessions; unknown reason |
211 (69%) of 305 LT-candidates | |||
Self-reported adherence: | |||
4–5 day/week: 146 (38%) | |||
1–3 day/week: 198 (51%) | |||
0 days/week: 41 (11%) | |||
Limongi ( |
NR | NR | NR |
Al-Judaibi ( |
NR | NR | NR |
LT, liver transplantation; NR, not reported
Four studies (
The aim of this systematic review was to evaluate the effect of prehabilitation on physical capacity and surgical outcome in patients actively waiting for OLT. Six out of eight studies demonstrated significant improvements in aerobic or physical capacity (
In the past, one other review and one meta-analysis have been conducted in patients with chronic liver disease to assess the effect of training on their physical capacity (
When elaborating on the physical effects of prehabilitation in OLT candidates, previous literature has shown that preoperative VO2 peak and MELD score are independent prognostic factors of mortality and duration of hospitalization during both the pre- and post-transplantation periods (
Debette-Gratien et al. were able to include 100% of eligible candidates in their study (
This review has several limitations. First of all, this review was not pre-registered on the PROSPERO database, which could have caused reduced transparency of the applied search strategy of this review. Secondly, there are certain limitations regarding the studied evidence: most included studies consisted of small patient populations, and focused on different primary outcomes, which made the comparison and analysis of the studies challenging. In addition, most of the studies were non-randomized, which leads to a reduction in the analysis strength of this review. Finally, as the values of the baseline and post-training outcomes are not independent of each other, and correlations were not reported by the individual studies, meta-analyses were not possible (
In our opinion, home-based training, which is supervised by a dedicated physical therapist and is combined with nutritional and educational support by a dietician, could be suitable for preoperative optimization until OLT. Patients might make some progress during these weeks of training, but, most importantly, deterioration of aerobic capacity could be prevented (
In conclusion, this systematic review found that prehabilitation in patients actively listed for OLT may improve aerobic and functional capacity, and, more importantly, that deterioration in aerobic and functional capacity could be countered by prehabilitation. Thereby, since no serious adverse events were reported and adherence to the training programs was high, we conclude that prehabilitation is safe and feasible in the OLT candidate. Thus, from our point of view, all patients awaiting OLT, especially the most physically frail ones, should be enrolled in predefined prehabilitation programs.
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
WJ and RH were involved in the review of the concept, literature search, design, manuscript preparation and review/editing of final manuscript. NM, FC, JK, and RJ were involved in the review of the concept and review/editing of final manuscript. All authors read and approved the final manuscript.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The authors would like to thank Wichor M. Bramer, PhD, as a biomedical information specialist from the Erasmus University Medical Center medical library for the collaboration in developing and updating the literary search strategy. The authors would also like to thank Sanne E. Hoeks, PhD as a clinical epidemiologist from the Erasmus University Medical Center for assistance with the statistical analyses of the results.
The Supplementary Material for this article can be found online at:
6MWD, six-minute walking distance; ERAS, enhanced recovery after surgery; ESLD, end-stage liver disease; F, delta point; GRADE, Grades of Recommendation, Assessment, Development and Evaluation for quality assessment of clinical studies; HR-QoL, health-related quality of life; i-CONTENT, international Consensus on Therapeutic Exercise aNd Training; ICU, intensive care unit; IQR, interquartile range; LFI, liver frailty index; MELD, model for end-stage liver disease; OLT, orthotopic liver transplantation; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PROSPERO, prospective register of systematic reviews; RCT, randomized controlled trial; SD, standard deviation; VO2 peak, oxygen consumption at peak exercise.