Review Article

Impact of Exercise on Physical Frailty in Patients With Chronic Liver Disease

Felicity R. Williams; Annalisa Berzigotti; Janet M. Lord; Jennifer C. Lai; Matthew J. Armstrong


Aliment Pharmacol Ther. 2019;50(9):988-1000. 

In This Article

Abstract and Introduction


Background: Physical frailty is common in chronic liver disease and the setting of liver transplantation. It is associated with poor quality of life, increased hospitalisation and mortality. Despite this, the impact of exercise in these patients remains poorly understood.

Aim: To summarise the impact of physical exercise on physical frailty in patients with chronic liver disease until after liver transplantation.

Methods: A MEDLINE and PubMed search was undertaken using the terms; "physical activity", "functional capacity", "exercise", "prehabilitation", "frailty", "liver cirrhosis", "liver failure", "liver transplantation" "chronic liver disease" and "end-stage liver disease" from January 1990 to June 2019.

Results: Eleven studies (five randomised controlled, five observational, one case study) demonstrated that exercise improves VO2 peak, anaerobic threshold, 6-minute walk distance, muscle mass/function and quality of life in patients with compensated and decompensated cirrhosis. Improvements were most significant with a combination of aerobic and resistance exercises at moderate-high intensity. The studies were small (n = 1–50) and mainly focused on supervised, hospital-based exercises, excluding patients with significant liver failure (MELD > 12). Seven studies (four randomised controlled and three observational) demonstrated that predominantly supervised (only one home-based) aerobic exercise after liver transplantation improves aerobic capacity, muscle mass/strength and quality of life. There was marked heterogeneity in timing, intensity and type of exercises.

Conclusion: Exercise improves key components of physical frailty (functional/aerobic capacity, sarcopenia) and quality of life in chronic liver disease and after liver transplantation. Understanding the type, compliance, intensity and duration of exercise and its impact on hard clinical outcomes should be the focus of future large controlled clinical trials.


Chronic liver disease (CLD) remains one of the most common causes of premature mortality in adults of working age.[1,2] The severity of disease, as determined using the Child-Pugh score and Model for End-Stage Liver Disease Sodium (MELD-Na), has remained one of the best determinants of prognosis in patients with CLD. However, in recent years studies have highlighted that patients with CLD who are physically frail and decline in function have excess mortality, which is not necessarily captured by the more orthodox scoring systems.[3] Understanding the true impact of physical frailty on clinical outcomes in patients with CLD and how to optimise them before (prehabilitation) and after (rehabilitation) hospital admissions, elective procedures (ie Transjugular intrahepatic portosystemic shunts) and surgery (especially transplantation) remains a challenge.

Frailty is traditionally defined as a clinical state of decreased physiologic reserve and increased vulnerability to health stressors.[4] While frailty is a multi-dimensional construct consisting of physical, psychosocial and other environmental components, physical frailty is the component that has been most frequently described in CLD. Physical frailty encompasses muscle mass, muscle strength, functional capacity (ie ability to complete activities of daily living) and aerobic exercise capacity (ie ability to utilise oxygen during physical exertion). A detailed description of the assessment of physical frailty (Table 1)[3–9] is beyond the scope of the current review.

CLD triggers metabolic, cellular, vascular and inflammatory changes in skeletal muscle biology, causing a reduction in muscle mass, strength and function, termed sarcopenia.[10] These biologic changes, along with under nutrition and physical inactivity[11] lead to a high prevalence (40%-70%) of physical frailty amongst patients with CLD.[12] In turn, physical frailty is associated with numerous poor clinical outcomes (quality of life, hospitilisation/length of stay, mortality), independent of severity of liver disease, in patients with CLD or having undergone liver transplantation.[7,13–21]

Exercise plays an important role in the primary prevention of many chronic diseases (ie cardiovascular, respiratory, metabolic)[17] as well as improving physical function in patients with sarcopenia.[22] However, it remains unclear whether exercise can be utilised as a therapeutic tool to improve the prevalence of physical frailty and consequently reduce mortality and frailty-associated complications in CLD. This review aims to summarise the existing knowledge regarding the utility and impact of physical exercise in patients with CLD and after liver transplantation. A MEDLINE and PubMed search was undertaken using the research terms; "physical activity", "functional capacity", "exercise", "prehabilitation", "frailty", "liver cirrhosis", "liver failure", "liver transplantation", "chronic liver disease" and "end-stage liver disease" from January 1990 to June 2019 (Figure 1).

Figure 1.

Flow chart of literature search and study selection. Abbreviation: NAFLD, non-alcoholic fatty liver disease