Improving the prognosis before and after liver transplantation: Is muscle a game changer?

Table 1 Main studies investigating the deleterious role of frailty, low muscle mass, sarcopenia and myosteatosis in patients undergoing pre-transplant assessment

Ref.	Patient selection	Patients, n	Sarcopenia, myosteatosis	Frailty parameters	Outcome	Results
Lai et al[15], 2019	Ambulatory cirrhotic patients awaiting LT	1014	Non applicable	LFI	Waiting list mortality	Frailty: 25%. HR = 1.82; 95%CI: 1.31-2.52; P < 0.001
Fozouni et al[48], 2020	LT recipients	241	Non applicable	LFI	Acute cellular rejection within 3 mo post-LT	Frailty: 19%. OR = 3.3; 95%CI: 1.2-9.3; P = 0.02
Lai et al[47], 2022	LT recipients	1166	Non applicable	LFI	LT LOS. ICU stay. Inpatient days within 3 mo post-LT. Overall survival (1-3 and 5-yr mortality)	Frailty: 21%. Prolonged LT LOS: OR = 2.00; 95%CI: 1.47-2.73. ICU stay: OR = 1.56; 95%CI: 1.12-2.14. Inpatient days within 3 mo. post-LT: OR = 1.72; 95%CI: 1.25-2.37. Overall survival: P = 0.02
Bhanji et al[41], 2018	Cirrhotic patients assessed for LT	675	L3-MA (HU). L3-SMI	Non applicable	HE. Mortality	Sarcopenia: 36%. HE: OR = 2.42; 95%CI: 1.43-4.10; P = 0.001. Mortality: Univariate HR = 2.02; 95%CI: 1.57-2.58; P < 0.001. Multivariate: HR = 2.15; 95%CI: 1.52-3.05; P < 0.001. Myosteatosis: 52%. HE: OR = 2.25; 95%CI: 1.32-3.85; P = 0.003. Mortality: Univariate: HR = 1.45; P = 0.004; 95%CI: 1.16-2.91. Multivariate: P = 0.69
Van Vugt et al[42], 2016	LT candidates/recipients	3804. Meta-analysis	SMI. Total psoas area	Non applicable	Waiting list mortality. Post-LT mortality	Waiting list mortality: HR = 1.72; 95%CI: 0.99-3.00; P = 0.02. Post-LT mortality: HR = 1.84; 95%CI: 1.11-3.05; P = 0.05
Bot et al[40], 2021	ESLD patients awaiting LT	262	L3-SMI (cm2/m2). L3-MA (HU)	Non applicable	Waiting list mortality	Low SMI: HR = 2.580; 95%CI: 1.055-6.308. MA: HR = 9.124; 95%CI: 2.871-28.970
Czigany et al[24], 2020	LT recipients	225	L3-SMI. L3-MA (HU)	Non applicable	Major morbidity. ICU stay. LT LOS	Sarcopenia: 37%. Myosteatosis: 44%. Major morbidity: OR = 2.772; 95%CI: 1.516-5.066; P = 0.001. ICU stay: 18 ± 25 vs 11 ± 21 d, P < 0.001. LT LOS: 56 ± 55 vs 33 ± 24 d, P < 0.001

LFI: Liver frailty index; HR: Hazard ratio; CI: Confidence interval; LT: Liver transplantation; OR: Odds ratio; LT LOS: Liver transplantation length of stay; ICU: Intensive care unit; L3-MA: Lumbar 3-muscle attenuation; HU: Hounsfield unit; L3-SMI: Lumbar 3-skeletal muscle index; HE: Hepatic encephalopathy; SMI: Skeletal muscle index; ESLD: End stage liver disease.

Table 2 Set of techniques to evaluate the physical activity as well as the quantity and quality of muscle

Technique	Goal	Advantages	Disadvantages
Physical activity assessment
IPAQ	Reflects physical activity over the last 7 d	Easier to implement. Understandable for the patient. Representative over 7 d	Subjective. Poor estimation by the patient
Pedometer	Measures walking activity	Inexpensive and easy to set up. Represents the physical activity of walking	Reliability decreases with walking speed. Could induce changes in patient’s habits. Does not measure other physical activities
Accelerometer	Measures walking activity	Takes slope and weight carried in consideration	Long to wear for good representation. Not sensitive to the inclination of the walk or the load worn during the walk. Could induce changes in patient’s habits
Anthropometric measurement
BC	Gives information on arm circumference and stage of muscle mass depletion	Very easy to perform (requires only a tape measure)	User dependent
MAMC (BC-TSF)	Gives information on arm muscle volume	Well described and easy to perform. Assesses muscle volume better than BC alone	User dependent. Requires a caliper
BIA	Allows to assess the body composition	Simple. Non-invasive. Reproductible	Requires specific equipment. Varies with fluid retention (common in cirrhosis)
Function tests
Handgrip	Allows to measure the strength of the forearm and wrist muscles	Low cost. Easy to perform. Gold standard	Not representative of total body strength
6MWT	Measures distance walked for 6 min	Easy to perform. Reflects endurance and general fitness	Caution in patients with cardiac and respiratory problems
LFI	Measures frailty of patients calculated with a score	Easy to perform. Little training	Not assessable in severe encephalopathy
Isokinetic	Measures the function and strength of a of group muscles	Gold standard. Reproducible	Cost. Requires training and collaboration. Caution in patients with cardiac and respiratory problems
Leg press	Measures the strength of the lower limbs	Simple device	Requires collaboration. Rougher assessment. Not well evaluated/used
Imaging techniques
US	Allows to measure the echogenicity of the muscle	Non-invasive. Not expensive	User dependent. Variability with fat thickness, position of the probe. Requires training
CT-scan	Allows to measure the surface of the muscle (easily) as well as its density	Clear image. Reproduceable	Radiation exposition
MRI	Can be used to evaluate the muscle surface. Measures the amount of fat within the muscle (PDFF)	Clear image. Reproduceable	Cost. Time consuming. Contra-indications (claustrophobia, pacemaker, etc)
DXA	Allows to measure the body composition (muscle, fat, water, etc)	Clear image. Reproduceable	Radiation exposition. Varies with fluid retention (common in cirrhosis)

IPAQ: International physical activity questionnaire; BMI: Body mass index; BC: Brachial circumference; TSF: Tricipital skin fold; MAMC: Mid-arm muscle circumference; BIA: Bio-impedance analysis; 6MWT: 6 min walk test; LFI: Liver frailty index; US: Ultrasound; CT-Scan: Computed tomography scan; MRI: Magnetic resonance imaging; PDFF: Proton density fat fraction; DXA: Dual x-ray absorptiometry.