Exercise training as an intervention for frailty in cirrhotic patients on the liver transplant waiting list: A systematic review

Table 1 Exercise prescription for cirrhotic patients on the waiting list for liver transplant

Ref.	Frequency	Intensity	Type	Time	Supervised?	In-person?
Al-Judaibi et al[30], 2019	In-person group: 1 to 5 times/wk. Remote group: 2 to 3 times/wk	-	In-person group: Aerobic and resistance training	-	Yes, remote group was supervised by videoconference	Yes
Lin et al[31], 2021	30 min a day, 5 times/wk	Frail and pre-frail: Aerobic: Encouraged to walk; purchasing a stationary bicycle or a pedal boat was suggested if the patient was at risk for walking. Resistance: Initial prescription at the time of evaluation with the physiotherapist. Weights or elastic bands can be used. Initially, 1 series of 10 repetitions, increase by 5 to 10 repetitions until reaching 30. Only then progress the load	Aerobic and resistance training	150 min of exercise per week	No	No, only if complications prevented the performance of the unsupervised exercise
Williams et al[32], 2019	Resistance: 20 min 2 times/wk. Aerobic: 10 min of brisk walking 3 times/d	Resisted: BORG between 12 and 14. Three levels: Low, moderate, and high. Aerobic: Increasing the number of steps	Aerobic and resistance training	Total of 12 wk, with reassessment at 6 and 12 wk and telephone contact 1 time/wk until 6 wk	No	No
Chen et al[33], 2020	Daily	Increase of 500 steps/d at each evaluation	Walking	Total: 8 wk, with a baseline assessment and every 2 wk	No	No
Lin et al[34], 2022	-	The group that used the app: The app’s algorithm established the intensity after an initial assessment by a professional	-	Baseline assessment and 4 wk after	No	No

The data were extracted and reported based on the Frequency, Intensity, Time, and Type recommendation (exercise frequency, intensity, time, and type of activity) and whether the program was supervised, in-person or remote.

Table 2 Impact of the exercise training programs on clinical outcomes, their relationship to adverse events, and adherence to the program

Ref.	Outcomes analysed	Adverse events	Adherence	NOS quality assessment
Al-Judaibi et al[30], 2019	Patients who participated in the rehabilitation program showed a tendency towards a decrease in length of stay and a reduction in readmission rates in patients undergoing liver transplantation. Although not statistically significant, the observed trend towards early discharge after liver transplantation was observed in patients in the intervention group			Selection: 4*. Comparability: 0*. Outcome: 3*
Lin et al[31], 2021	LFI: Patients more adherent to the prehabilitation program have better results. Frailty is associated with mortality. An improvement of 0.3 in LFI is potentially associated with improved survival. 6MWT: Tendency of improvement with the pre-rehabilitation program, especially in the most adherent patients, after visit 4. Frailty is associated with mortality. Gait speed: There was no change with pre-rehabilitation. Frailty is associated with mortality. Frailty is more prevalent in females, higher BMI (as assessed by the 6MWT and GST), cirrhosis from alcohol or NASH, HB values, albumin, and bulky appearance, do not correlate with MELD. Patients with COPD and CVD are frailer by 3 frailty assessment metrics		Reposted by the patient at follow-up assessment: non-adherent < 20%, partially adherent: 20%-79%, adherent: ≥ 80%. Members: 38%. Partially adherent: 51% and non-adherent: 11%. Adherence to physical therapy was independently associated with increased survival	Selection: 2*. Comparability: 0*. Outcome: 2*
Dunn et al[35], 2016	Karnofsky scale and Rossow-Breslau indicated habitual physical activity performance close to normal. Comparing with objective data of counting daily steps, it showed that 75.9% of waking time was in sedentary activity. There was a significant association between the percentage of sedentary behaviour and deaths on the waiting list			Selection: 4*. Comparability: 0*. Outcome: 3*
Williams et al[32], 2019	SPPB, ISWT: Improved at 6 wk and no improvement at 12 wk. Step count: Improvement in the index at 12 wk. Quality of life improves in the 12th wk, mainly regarding mobility	No events	Adherence up to 6 wk: 82% step target and 90% resistance exercises. Already at 12 wk, they dropped to 53% and 78%, respectively	Selection: 4*. Comparability: 0*. Outcome: 3*
Ney et al[36], 2017	IPAQ: 47%, 38% and 15% of patients had low, moderate and high activity levels, respectively. The main barrier perceived for not performing physical exercise was fatigue			Selection: 2*. Comparability: 0*. Outcome: 2*
Lai et al[37], 2016	Fried Frailty Index > 3 frail. 6MWT: Frail with less walking distance. Frail: Less sit and stand up and lower isometric knee extension strength-tendency of critically ill patients to be more fragile			Selection: 2*. Comparability: 0*. Outcome: 2*
Chen et al[33], 2020	The control group had more patients who walked less than 2500 steps/d. 6MWT: Greater distance walked in the group with home exercises. CPET: No difference between groups. Computed tomography: Increased psoas muscle mass in the group with home exercises. Quality of life: No differences between groups	No events		Selection: 4*. Comparability: 2*. Outcome: 3*
Oikonomou et al[38], 2022	Significant correlation between LFI and physical activity level. LFI: Best in active (active: 3.75, sedentary: 4.42). No frail in the active group. Six frails in the sedentary group. Greater distance in active compared to sedentary (458.2 × 324.7). Peak VO2 and the highest AT in the active			Selection: 3*. Comparability: 0*. Outcome: 2*
Lin et al[34], 2022	They were considered fragile if LFI was 4.5 or greater, 6MWT was less than 250 m, or GST was less than 0.8 m/s. Patients who walk less than 1200 steps/d have a higher LFI. Every additional 500 steps taken per day reduces the risk of hospitalisation by 5% and the risk of death by 12%. Patients in the group using an exercise app took more daily steps. Daily step count was moderately correlated with frailty metrics, and frail patients walked less than their less frail peers by any metric

NOS: Newcastle-Ottawa Scale; LFI: Liver Frailty Index; 6MWT: Six-minute walking test; BMI: Body mass index; GST: Gait speed test; NASH: Non-alcoholic steatohepatitis; HB: Haemoglobin; MELD: Model for End-Stage Liver Disease; COPD: Chronic obstructive pulmonary disease; CVD: Cardiovascular disease; SPPB: Short Physical Performance Battery; ISWT: Incremental shuttle walk test; IPAQ: International Physical Activity Questionnaire; CPET: Cardiopulmonary exercise testing; VO₂: Oxygen uptake; AT: Anaerobic threshold.