Loschi TM, Baccan MDTA, Pereira EC, Dellabarba TDLC, Boteon APCS, Boteon YL. Telerehabilitation for frail cirrhotic patients awaiting liver transplant: A safe, effective strategy to improve outcomes. World J Hepatol 2025; 17(10): 110856 [PMID: 41179717 DOI: 10.4254/wjh.v17.i10.110856]
Corresponding Author of This Article
Yuri L Boteon, MD, PhD, FACS, Professor, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Faculdade Israelita de Ciências da Saúde Albert Einstein, 627/701 Albert Einstein Avenue, São Paulo 05652-900, Brazil. yuri.boteon@einstein.br
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Clinical Trials Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Thais Mellato Loschi, Melline D T A Baccan, Elaine C Pereira, Thaise D L C Dellabarba, Amanda P C S Boteon, Transplant Centre, Hospital Israelita Albert Einstein, São Paulo 05652-900, Brazil
Thais Mellato Loschi, Yuri L Boteon, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo 05652-900, Brazil
Author contributions: Boteon YL, Boteon APCS and Loschi TM conceived the idea and designed the study. Boteon YL, Boteon APCS and Loschi TM performed the literature search; Loschi TM, Baccan MDTA, Pereira EC and Dellabarba TDLC performed the physiotherapy sessions and collected the data; Boteon YL, Boteon APCS and Loschi TM drafted and approved the final manuscript; Baccan MDTA, Pereira EC and Dellabarba TDLC reviewed the draft and approved the final manuscript. All authors contributed to editing and approved the final manuscript version.
Institutional review board statement: This study was reviewed and approved by the local Ethical Review Board (Hospital Israelita Albert Einstein CAAE number 40105420.7.0000.0071, opinion 4.982.351).
Clinical trial registration statement: This study has not been registered at https://clinicaltrials.gov.
Informed consent statement: All the individuals who participated in this study provided their written informed consent prior to study enrolment.
Conflict-of-interest statement: This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement:
No additional data are available.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yuri L Boteon, MD, PhD, FACS, Professor, Instituto Israelita de Ensino e Pesquisa Albert Einstein, Faculdade Israelita de Ciências da Saúde Albert Einstein, 627/701 Albert Einstein Avenue, São Paulo 05652-900, Brazil. yuri.boteon@einstein.br
Received: June 17, 2025 Revised: July 4, 2025 Accepted: September 17, 2025 Published online: October 27, 2025 Processing time: 132 Days and 20.6 Hours
Abstract
BACKGROUND
Telerehabilitation can help overcome geographic barriers and expand access to physical rehabilitation for patients with chronic liver disease.
AIM
To evaluate the impact of adherence to a videoconference-supervised telerehabilitation programme on frailty, functional capacity, and quality of life in pre-frail or frail cirrhotic patients awaiting liver transplantation.
METHODS
We conducted a non-randomised controlled clinical trial involving patients listed for liver transplantation from January 2021 to May 2023. Frailty was assessed using the Liver Frailty Index (LFI). Participants were enrolled in a 12-week telerehabilitation programme and classified as adherent (≥ 50% sessions) or non-adherent. Functional capacity was measured using the 4-minute step test (4MST), and quality of life was evaluated with the 36-Item Short Form Health Survey (SF-36) questionnaire.
RESULTS
Fifty-seven pre-frail or frail patients were included in the study and enrolled in the telerehabilitation programme. Adherence was observed in 29.8% of participants. At baseline, non-adherent patients had higher mean LFI scores (4.24 vs 4.03, P < 0.001). Over time, the LFI score increased by 0.11 in non-adherent patients, while adherent patients experienced a mean score reduction of 0.54 (final mean LFI score: 3.2). Adherent patients also demonstrated enhanced heart rate responses in the 4MST (P < 0.001) and greater improvements in the physical functioning, vitality, and mental health domains of the SF-36. No serious adverse events were reported.
CONCLUSION
The videoconference-supervised telerehabilitation programme was safe and effective in reducing frailty and improving functional outcomes and quality of life in adherent cirrhotic patients on the liver transplant waitlist.
Core Tip: This study demonstrates that a supervised 12-week telerehabilitation programme is safe, feasible, and effective in addressing frailty among cirrhotic patients awaiting liver transplantation. Adherent patients showed significant improvements in frailty scores (Liver Frailty Index), functional capacity (4-minute step test), and quality of life (36-Item Short Form Health Survey domains). These findings support the use of telerehabilitation as a practical strategy for pre-transplant optimisation in a high-risk, geographically dispersed population.
Citation: Loschi TM, Baccan MDTA, Pereira EC, Dellabarba TDLC, Boteon APCS, Boteon YL. Telerehabilitation for frail cirrhotic patients awaiting liver transplant: A safe, effective strategy to improve outcomes. World J Hepatol 2025; 17(10): 110856
Frailty is a multidimensional clinical syndrome characterised by reduced physiological reserve and resilience, often associated with sarcopenia and diminished functional capacity[1]. Among patients with cirrhosis awaiting liver transplantation, frailty is common and contributes to worse pre- and post-transplant outcomes, including increased risks of mortality, hospitalisation, prolonged recovery, and loss of independence[2-5]. Multiple pathophysiological mechanisms contribute to frailty in this population. These include hyperammonemia[6], hormonal imbalances[2,7-10], pro-inflammatory mediators[2,11], intestinal dysbiosis[2,12], and altered amino acid metabolism[13]. Additionally, clinical complications such as malnutrition, ascites, hepatic encephalopathy, sarcopenic obesity, and diuretic therapy exacerbate functional decline[2]. As chronic liver disease progresses, frailty tends to worsen unless addressed through targeted interventions, particularly physical exercise, which remains a cornerstone of frailty management[14].
The benefits of regular physical activity in patients with cirrhosis are well established. These benefits are enhanced when exercise is tailored to the individual’s condition and capabilities[15,16]. Although a standardised prescription for exercise for this population is lacking, maintaining light to moderate physical activity-whether aerobic, resistance-based, or both-is widely recommended, provided that patients are adequately evaluated, guided, and supported throughout the intervention. Structured rehabilitation programmes combining aerobic and resistance exercises over 4 to 12 weeks have shown promising results in reversing frailty and improving function in patients with advanced liver disease[17].
Telerehabilitation may offer an accessible, cost-effective solution to the logistical and geographic barriers faced by many liver transplant candidates. This study aimed to assess the impact of adherence to a structured telerehabilitation programme on frailty, functional capacity, and quality of life in patients with cirrhosis listed for liver transplantation who were pre-frail or frail at baseline.
MATERIALS AND METHODS
Study design and patient selection
This non-randomised controlled clinical trial included a convenience sample of consecutive patients with end-stage liver disease listed for liver transplantation at a tertiary hospital in Brazil between January 2021 and May 2023. All eligible patients during the study period were invited to participate. As this was an exploratory study conducted under real-world conditions, no formal sample size calculation was performed a priori.
Exclusion criteria included the presence of neurological or musculoskeletal disorders that prevented physical activity, severe acute liver failure, uncontrolled cardiopulmonary conditions, hepatopulmonary syndrome, and refusal to participate in remote rehabilitation. The study was approved by the Research Ethics Committee of Hospital Israelita Albert Einstein (CAAE: 40105420.7.0000.0071; Opinion No. 4.982.351).
Assessments of frailty, functional capacity, and quality of life
Participants were evaluated at three timepoints: Visit 1 (at listing for liver transplantation), Visit 2 (six weeks after Visit 1), and Visit 3 (twelve weeks after Visit 1). At each visit, sociodemographic data, Model for End-Stage Liver Disease- Sodium (MELD-Na) scores, liver disease aetiology, history of decompensations, and comorbidities were recorded.
Frailty was assessed using the Liver Frailty Index (LFI)[18], which includes three physical performance components: (1) The average of three handgrip strength measurements; (2) Time to complete five chair stands without using the arms; and (3) Ability to maintain static balance in three positions (parallel, semi-tandem, and tandem stances). Based on the total LFI score, patients were classified as robust, pre-frail, or frail.
Functional capacity was measured using the 4-minute step test (4MST)[19], during which patients were instructed to step up and down a standard platform at their own pace for 4 minutes. Vital signs were recorded before the test, during the second and fourth minutes, and at 2 minutes post-recovery. Quality of life was evaluated using the 36-Item Short Form Health Survey (SF-36) questionnaire[20].
Screening, group allocation, and rehabilitation intervention
All patients listed for liver transplantation and not meeting the exclusion criteria were evaluated at Visit 1 and received standard guidance to engage in 150 minutes of moderate-intensity walking per week. This recommendation-based on the "talk test" or a Borg perceived exertion level of 12-14-was provided to all patients as part of routine care but was not used as an inclusion or grouping criterion.
Frailty classification based on the LFI at Visit 1 guided inclusion in the telerehabilitation programme study. Patients classified as robust were excluded from the telerehabilitation programme and follow-up assessments but continued to receive general physical activity recommendations. Patients classified as pre-frail or frail were included in the telerehabilitation group and invited to participate in the intervention and complete Visits 2 and 3. For all patients, including those who did not undergo transplantation, the date and cause of death (if applicable) were recorded.
Supervised exercise programme via telerehabilitation
Patients identified as pre-frail or frail were invited to participate in a 12-week telerehabilitation programme comprising two supervised sessions per week (approximately 1 hour each). Sessions were delivered in small groups (up to 10 participants) stratified by frailty level. Exercises included functional movements targeting strength, resistance, balance, and flexibility of the trunk and upper and lower limbs. Resistance was applied using simple, low-cost tools such as elastic bands, balls, sticks, and water bottles.
Participants were encouraged to maintain moderate exercise intensity (Borg 12-14 or guided by the talk test). Sessions were conducted via the Zoom® videoconferencing platform (Version 5.4.7, 2020), using two-way video and audio to allow for real-time interaction between patients and physiotherapists. Four experienced physiotherapists, specialised in pre- and post-transplant rehabilitation, led the sessions per the structured study protocol.
Attendance was monitored throughout the intervention. Adherence was calculated as the percentage of sessions attended (sessions attended/total offered). Participants attending at least 50% of the sessions were classified as adherent, while those attending less than 50% were considered non-adherents.
Statistical analysis
Quantitative variables were described using means, SD, medians, minimums, maximums, and quartiles. Qualitative variables were presented as frequency distributions. Graphical analyses supported result interpretation.
Associations between qualitative variables and study groups (adherent vs non-adherent) were assessed using Pearson’s χ2 test or Fisher’s exact test, as appropriate. Comparisons between groups for quantitative variables were performed using Student’s t-test. The McNemar test was used to compare the occurrence of complications and hospitalisations between Visits 2 and 3.
Changes in frailty classification (LFI categories) across timepoints were analysed using the marginal homogeneity test for ordinal categorical variables. Generalised Additive Models for Location, Scale, and Shape (GAMLSS) were applied to model the longitudinal impact of adherence on outcomes of interest, including performance metrics and physiological responses.
A post hoc power analyses was performed to evaluate whether the sample size achieved sufficient statistical power to detect clinically meaningful differences between groups. All P-values were two-tailed, and statistical significance was set at P < 0.05. Analyses were conducted using R software, version 4.1.1.
RESULTS
Patient selection and baseline characteristics
One hundred and five patients were assessed using the LFI at Visit 1. Patients classified as robust (n = 10) were excluded from the telerehabilitation programme but received standard recommendations for moderate-intensity walking. Pre-frail (n = 66) and frail (n = 29) patients were considered eligible for inclusion. Of those, 38 patients were not included in the telerehabilitation programme because of refusal or lack of technological resources, early transplantation, death or loss to follow-up, and clinical conditions that posed a safety risk for unsupervised rehabilitation (such as cognitive impairment, risk of falls, orthopaedic limitations, or haemodynamic instability identified during in-person evaluation). Details of the patient selection process are shown in Figure 1.
Figure 1 Patient flow through screening, allocation, and telerehabilitation phases.
Patients listed for liver transplantation were assessed at Visit 1 and screened using the Liver Frailty Index. Robust individuals were excluded from the telerehabilitation programme but received standard walking recommendations. Pre-frail and frail patients were evaluated for inclusion; 46 were excluded due to refusal, unavailability of resources, clinical contraindications, or early loss to follow-up. A total of 57 patients initiated telerehabilitation, of whom 17 were considered adherent (≥ 50% session attendance) and 40 were non-adherent.
Of the 57 patients included in the telerehabilitation programme, the mean MELD-Na was 16.58 (SD 5.33), LFI was 4.17 (SD 0.73), and 4MST was 62.7 steps (SD 20.63). The median frequency of participation in telerehabilitation sessions was 23% (interquartile range 0-61). Among the patients, 70.18% (n = 40) were classified as non-adherent to the programme, while 29.82% (n = 17) were considered adherent, based on session attendance. Table 1 summarizes the sociodemographic, clinical, and outcome variables.
Table 1 Sociodemographic and clinical characteristics of the 57 patients included in the telerehabilitation programme.
Variable (classes)
n (%)
Male, gender
30 (52.63)
Aetiology of liver disease
Cirrhosis due to alcohol
16 (28.07)
Hepatitis C virus cirrhosis
4 (7.02)
Primary sclerosing cholangitis
2 (3.51)
Late retransplant
10 (17.54)
Autoimmune hepatitis
4 (7.02)
Cryptogenic cirrhosis
7 (12.28)
Metabolic dysfunction-associated steatohepatitis
7 (12.28)
Other
7 (12.28)
Encephalopathy, yes
22 (38.6)
Hepatocellular carcinoma, yes
8 (14.04)
Upper gastrointestinal bleeding, yes
9 (15.79)
Refractory ascites, yes
18 (31.58)
Portal vein thrombosis, yes
3 (5.26)
Outcome
Contraindicated for transplantation/discharge from the transplant program
Of the 57 patients included in the telerehabilitation programme (75.43% were pre-frail and 24.56% frail), 33 attended and were reassessed at Visit 2. Of these, 15 (45%) were ultimately classified as adherent and 18 (55%) as non-adherent; 6.07% were robust, 75.75% were pre-frail and 18.18% were frail. Twenty patients attended Visit 3, with 13 (65%) being adherent and seven (35%) non-adherent (all of whom were already classified as non-adherent at Visit 2). Regarding frailty, 20% were robust, 55% were pre-frail and 25% were frail. Despite a decrease in the number of patients completing follow-up assessments, the mean LFI values showed a progressive reduction across visits: 4.17 (SD 0.73) at Visit 1, 4.06 (SD 0.65) at Visit 2, and 3.81 (SD 0.92) at Visit 3.
Table 2 presents the association between the study groups (adherent vs non-adherent) and the clinical and demographic variables. No statistically significant differences were observed between groups across the evaluated variables, including sex, blood type, aetiology of liver disease, and key complications such as hepatic encephalopathy, ascites, hepatocellular carcinoma, and refractory ascites. Transplant list status and prior surgical history were also similar between the groups.
Table 2 Cross-analysis of clinical and demographic characteristics between adherent and non-adherent patients, n (%).
At the time of initial assessment, 9.52% (n = 10) of patients were robust, 62.85% (n = 66) were pre-frail, and 27.61% (n = 29) were frail based on the LFI. Among the 57 patients included in the telerehabilitation programme, 75.43% were pre-frail and 24.56% were frail. No statistically significant shifts in LFI classification were observed across timepoints (Supplementary Table 1).
Impact of the telerehabilitation programme on frailty
Figure 2 displays the trajectory of LFI values over the three study visits for adherent and non-adherent patients. Patients in the Adherent Group consistently showed lower mean LFI values compared to the Non-Adherent Group (P < 0.001). Over the 12-week follow-up, the Adherent Group demonstrated a reduction of 0.54 points in LFI, reflecting improvement in frailty status. In contrast, the Non-Adherent Group experienced a slight increase of 0.11 points, indicating progressive frailty.
Figure 2 Evolution of Liver Frailty Index scores over time in adherent and non-adherent participants.
Bar graphs represent mean Liver Frailty Index values with standard deviations at each study visit (V1, V2, and V3). The adherent group demonstrated a progressive reduction in frailty scores across visits, while the non-adherent group showed a slight increase. Dotted lines indicate the linear trend for each group.
Analysis of the relative treatment effect (RTE) of the intervention on LFI values over time, presented in Figure 3, revealed a declining RTE trajectory in the Adherent Group, indicating a consistent improvement in frailty status across visits. In contrast, the Non-Adherent Group exhibited a modest upward trend in RTE, suggesting worsening or stagnation of frailty.
Figure 3 Relative treatment effect values for the Liver Frailty Index across study visits and participant groups.
A: The overall relative treatment effect (RTE) values show a slight reduction in frailty over time for the entire sample; B: RTE trajectories are stratified by adherence group: Adherent patients exhibited a progressive reduction in frailty (decreasing RTE), while non-adherent participants showed a slight increase. RTE values above 0.5 indicate higher frailty; values below 0.5 indicate improvement. RTE: Relative treatment effect.
Impact of the telerehabilitation programme on functional capacity
In GAMLSS analyses (Table 3), patients in the Adherent Group took significantly more steps in the 4MST at Visit 3 than the Non-Adherent Group (P = 0.029), reflecting improved functional capacity. Additionally, heart rate in the fourth minute of the test was significantly higher among adherent patients (P < 0.001), indicating better cardiorespiratory response (Supplementary Table 2).
Table 3 Results of the four-minute step test across study visits and groups.
Impact of the telerehabilitation programme on quality of life
As shown in Figure 4 and Supplementary Table 3, the Adherent Group scored higher in the physical functioning, vitality, and mental health domains of the SF-36 questionnaire. Both groups showed improvement in the pain domain at Visit 2 (P = 0.028), but the Visit 3 results were inconclusive, likely due to the smaller sample size.
Figure 4 Descriptive trends of 36-Item Short Form Health Survey quality of life domains across study visits in adherent and non-adherent patients.
Each panel represents one domain of the 36-Item Short Form Health Survey questionnaire (Physical Functioning, Pain, General Health, Vitality, Social Functioning, and Mental Health). Adherent participants (red line) showed modest improvements across most domains over time, while non-adherent participants (blue line) exhibited stable or worsening scores. These trends highlight the potential impact of telerehabilitation adherence on perceived quality of life. SF-36: 36-Item Short Form Health Survey.
Telerehabilitation program safety
Over the 28-month data collection period, two minor complications were reported, both unrelated to the intervention. One patient experienced chills and discontinued the session; he was later diagnosed with cholangitis. Another patient experienced nausea during a session, which resolved with rest and did not require medical attention. No adverse events directly attributable to the telerehabilitation programme were observed.
Post hoc power analysis
A post hoc power analysis based on the observed change in the LFI among participants was conducted. The Adherent Group showed a mean reduction of 0.54 points in LFI over the 12-week period, while the Non-Adherent Group showed a slight increase of 0.11 points. Using the baseline SD of 0.73, the estimated effect size (Cohen’s d) was approximately 0.74, indicating a moderate effect. Considering the sample sizes of patients reassessed at the final follow-up visit (n = 13 for the Adherent Group and n = 7 for the Non-Adherent Group), and using a two-sided independent t-test with an alpha of 0.05, the calculated statistical power was 32.1%.
DISCUSSION
This study demonstrated that a videoconference-supervised telerehabilitation programme is both safe and effective in managing frailty among patients with chronic liver disease on the liver transplant waitlist. In addition to reducing frailty levels, the programme improved functional capacity and quality of life among adherent participants. By delivering care remotely, the intervention addressed critical barriers such as the geographic distance from transplant centres and the high prevalence of physical frailty in this population.
Cirrhosis leads to physical frailty and sarcopenia, which often co-occur[21]. Previous studies report a frailty prevalence between 18% and 59% in this population[22-25]. In our cohort, 27.6% of patients were initially classified as frail. The high prevalence of frailty observed likely contributed to the low adherence rate, as frailty may hinder engagement in structured physical activity. Although the MELD-Na scores, comorbidity patterns, and cirrhosis complications did not differ significantly between groups (indicating that adherence to the telerehabilitation program was not clearly associated with these variables), adherent patients had lower baseline frailty scores (P < 0.03), suggesting that milder frailty may facilitate participation in rehabilitation. In addition, adherence to the telerehabilitation program was not clearly associated with measured comorbidity patterns. Based on these findings, we advocate for the incorporation of routine frailty screening using validated tools (such as the LFI) into pre-transplant care in Brazil, as poor outcomes are linked to frailty[21,26,27].
Our telerehabilitation protocol targets physical frailty, evaluated using the LFI, which measures grip strength, balance, and mobility[28]. Multicenter studies have validated that an LFI score ≥ 4.5 indicates a 1.9-fold increased mortality risk, while a 0.1 LFI score increase is linked to double the risk of death or delisting[29-31]. In our analysis, non-adherent patients had a mean LFI value of 4.4 compared to 3.49 among adherent patients (P < 0.001). Moreover, adherent participants demonstrated a reduction of 0.54 in the LFI score, while non-adherent individuals exhibited an increase of 0.11, highlighting the potential of supervised telerehabilitation to reverse frailty.
Despite growing evidence on telerehabilitation in other chronic diseases, only one prior study has assessed supervised telerehabilitation in cirrhotic patients awaiting liver transplantation. Other studies have used unsupervised interventions, with none reporting serious adverse events[17,32-36]. A recent systematic review compared telerehabilitation to in-person rehabilitation, concluding that both approaches yield similar functional and quality-of-life outcomes[37]. The cost-effectiveness and safety of telerehabilitation were studied in populations with diverse conditions-cardiac[38-40], neurological[41,42], oncological[43], and musculoskeletal[44-48]. Functional and quality-of-life assessments varied significantly by population. Most studies used videoconferencing as the sole tool or combined it with apps and email. Our protocol used a low-cost, synchronous videoconferencing platform to conduct real-time sessions with professional supervision, ensuring safety and promoting adherence. Patients participated from distances of up to 3500 km, demonstrating the programme’s feasibility across diverse settings.
Functional assessments are critical for monitoring and targeting frailty. In cirrhotic patients, walking less than 250 m in the 6-minute walk test affects clinical outcomes; every 100-metre decrease doubles the mortality risk[49]. This test needs a flat, enclosed 30-metre corridor free of traffic, complicating its routine clinical implementation. Thus, the 4MST served as a feasible alternative in our study. Previously, only one article utilised the step test in cirrhotic patients to assess exercise response[50]. In our study, adherent patients showed improved step counts and a more favourable cardiovascular response by the end of the programme, supporting the utility of the 4MST in clinical follow-up. Notably, some patients were unable to complete the test due to joint pain, oedema, or hernias-limitations not captured by the LFI alone. These findings underscore the importance of using complementary functional tools. Future studies should thoroughly examine haemodynamic variables during exertion, especially since many patients take beta-blockers that may influence heart rate.
Quality of life, assessed using the SF-36 questionnaire, improved in several domains for adherent patients. Higher scores in physical functioning, vitality, mental health, and social functioning were observed. These findings are consistent with better functional and frailty scores and reflect the psychological benefits of structured, supportive rehabilitation. Patients cited various reasons for adherence, including perceived physical improvement, scheduled structure, physiotherapist engagement, and the programme’s low cost. These likely contributed to improved mental health. Strengthening psychological support during pre-transplant care may further enhance such benefits.
Adherent patients also developed a sense of community with peers and the care team, reinforcing social support networks. This social engagement, combined with multidisciplinary evaluation at listing, likely contributed to quality-of-life improvements. Most patients reported no major social vulnerabilities (63%), though financial and family support issues were noted in a minority (28% and 9%, respectively). Pain scores increased over time in both adherent and non-adherent patients, likely reflecting disease progression.
The 12-week programme duration was informed by prior studies showing benefit within this timeframe[30,32,51-54]. While this approach is widely used and accepted, no standardised guideline currently defines the optimal programme duration[17,55]. Similarly, although all patients were advised to walk 150 minutes per week as part of usual care, the independent impact of this recommendation remains unclear and warrants further investigation[17,55].
The primary limitation of this study was the low adherence rate, with only 29.8% of patients completing at least 50% of the sessions. This led to unbalanced group sizes and may have introduced bias. Nonetheless, the clinical improvements observed in adherent participants suggest that meaningful benefit is achievable. Importantly, the remote delivery model itself offered key practical advantages-such as accessibility for geographically distant patients and continuity of care despite logistical barriers-demonstrating feasibility in real-world conditions.
Moreover, given that adherent patients had lower baseline frailty scores, and pre-frail patients were more likely to complete follow-up visits, it is possible that observed improvements primarily reflect the responsiveness of pre-frail individuals. The limited number of frail patients in the adherent group precluded a stratified efficacy analysis. Future studies should explore whether frail and pre-frail patients benefit equally from rehabilitation and identify tailored strategies to improve engagement among patients with more advanced frailty.
The progressive reduction in LFI scores observed over time must be interpreted in the context of attrition across follow-up visits, which limits the ability to draw definitive conclusions about longer-term outcomes. However, the consistent improvement in LFI values among adherent participants supports the potential effectiveness of the telerehabilitation intervention. We acknowledge the risk of attrition bias, as patients who completed follow-up assessments may represent a more motivated or clinically stable subgroup. Additionally, the increasing number of robust and pre-frail classifications by Visit 3 suggests that those with milder baseline frailty were more likely to remain engaged, giving rise to the hypothesis that telerehabilitation may be particularly effective in stabilising or reversing early frailty. These limitations are inherent to real-world studies involving frail, high-risk populations and further underscore the importance of implementing strategies to enhance adherence and retention in future trials.
Adherence remains a challenge in this population. A systematic review showed that telerehabilitation had a higher completion rate (93%) compared to in-person rehabilitation (70%) in patients with chronic lung disease[56]. Among heart failure patients, adherence was also higher in telerehabilitation (71%) vs face-to-face participants (30%)[39]. Studies also show that cirrhotic patients have lower adherence rates than other chronic disease groups[54]. Lin et al[34] found that completing 80% of an unsupervised rehabilitation programme improved survival. However, only 38% of patients were adherent, with 51% partially adherent (20%-79% compliance). Williams et al[33] evaluated a 12-week unsupervised programme, noting 82% adherence by week 6 for the step goal and 90% for resistance exercises. However, adherence dropped to 53% and 78%, respectively, by week 12 due to a lack of telephone monitoring after Week 6. In our study, the absence of ongoing motivational contact (e.g., phone follow-ups) may have contributed to low participation. Strategies such as regular check-ins and reinforcing the benefits of physical activity during clinical visits are being explored to improve engagement.
Additional limitations preclude definitive conclusions regarding the full range of potential influencing factors, including the limited sample size, the use of a convenience sample, the study’s non-randomised design, and limited power to assess hard clinical outcomes such as hospitalisation or mortality. Subgroup analyses comparing frailty strata (frail vs pre-frail) and adherence categories (adherent vs non-adherent) were exploratory and likely underpowered to detect subtle but clinically meaningful differences. A post hoc power analysis highlighted that, despite a moderate effect size (Cohen’s d ≈ 0.74), the study was underpowered to detect clinically meaningful changes in frailty due to the small sample size at the final time point. These limitations underscore the need for larger, multicenter trials with extended follow-up to validate these findings and refine intervention strategies.
Nonetheless, the development and implementation of a scalable, low-cost telerehabilitation protocol tailored to frail liver transplant candidates is a key contribution of this study. Our results suggest that frailty can be improved using low-cost resources (like mobile phones with internet, water bottles, broom handles, elastic bands, and balls) rather than expensive wearable accessories.
CONCLUSION
The videoconference-supervised telerehabilitation programme was safe and feasible for patients with cirrhosis on the liver transplant waitlist who are frail or at risk of developing this condition. Among adherent patients, significant improvements in frailty, functional capacity, and quality of life were observed. However, these findings are exploratory and should be interpreted with caution due to the study’s small sample size, non-randomised design, and high attrition. Promoting adherence is essential to maximise programme impact and will require a better understanding of individual barriers, targeted support strategies, and active engagement from multidisciplinary transplant teams.
Footnotes
Provenance and peer review: Invited article; Externally peer reviewed.
Peer-review model: Single blind
Corresponding Author's Membership in Professional Societies: International Liver Transplantation Society.
Specialty type: Gastroenterology and hepatology
Country of origin: Brazil
Peer-review report’s classification
Scientific Quality: Grade B, Grade C
Novelty: Grade B, Grade B
Creativity or Innovation: Grade B, Grade B
Scientific Significance: Grade B, Grade B
P-Reviewer: Cui X, PhD, FRCS (Gen Surg), China S-Editor: Qu XL L-Editor: A P-Editor: Zhang YL
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