Training in Patients with Cirrhosis

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© Springer Nature Switzerland AG 2020
P. Tandon, A. J. Montano-Loza (eds.)Frailty and Sarcopenia in

7. Exercise Training in Patients with Cirrhosis

Graeme M. Purdy1, Kenneth J. Riess1, 2, Kathleen P. Ismond3 and Puneeta Tandon3, 4  

Department of Physical Therapy, Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, AB, Canada

School of Health and Life Sciences, Northern Alberta Institute of Technology, Edmonton, AB, Canada

Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada

Department of Medicine, Cirrhosis Care Clinic, University of Alberta, Edmonton, AB, Canada



Puneeta Tandon


ExercisePhysical activitySedentary behaviourDeconditioningSafety


Cirrhosis is a chronic progressive disease that affects not only the liver but also multiple other organ systems, including both the neuromuscular and cardiorespiratory systems [1]. As reviewed in other chapters, a multitude of factors inherent to the disease lead to significant deconditioning, sarcopenia, and frailty, which impacts the patients’ activities of daily living. Patients living with cirrhosis have an aerobic capacity (as measured by peak VO2) 60–82% lower than healthy, aged-matched adults [2]. Patients also experience significant peripheral muscle dysfunction [3], bone density loss [4], fatigue [5], and increased fall risk [6]. Exercise programming can target these impairments and contribute to the improved function of patients with cirrhosis [7].

With liver disease, patients experience what has been described as “a downward spiral of deconditioning” [8] attributed to low levels of physical activity and high levels of sedentary behaviour [9, 10]. Contributing factors include [1113]:

  • A lack of cirrhosis- or chronic disease-specific programming

  • High levels of fatigue and impaired exercise tolerance

  • A paucity of evidence-based tools for clinicians to inform prescribing and monitoring of safe, effective programming

  • Concurrent cognitive impairment related to hepatic encephalopathy

  • Lack of self-efficacy

In other chronic disease populations (e.g., cancer, diabetes, cardiac disease, pulmonary hypertension), specific exercise guidelines have been published [1419]. The American Association for the Study of Liver Diseases has recommended personalized exercise interventions for patients with cirrhosis [3]. Moreover, it is recommended that patients awaiting solid organ transplantation complete exercise training [5, 2023]. However, the clinical application of exercise programming in cirrhosis has been slow to be integrated into routine care [2428].

This chapter will briefly review sarcopenia and frailty as they relate to exercise, provide an overview of the literature about the role of exercise in attenuating cirrhosis-related complications, outline a recommendation on how to screen and assess patients before initiating an exercise programme, and offer practical, evidence-based exercise programming considerations and examples pertinent for a range of patient levels. The measurement tools used to assess the impact of an exercise programme on sarcopenia and frailty have been covered in other chapters and will not be reviewed in great detail here.

The operationalization of this chapter’s recommendations into a clinical context will vary from centre to centre largely dependent upon the resources available to the clinician. Ideally, all patients will have access to an exercise specialist to guide them through a safety screen, physical assessment, and testing for sarcopenia and frailty culminating in a personalized exercise prescription. Recognizing that this is not a reality for most clinical settings, and recognizing that many primary care physicians also may have a level of discomfort prescribing exercise to patients with cirrhosis, we include resources so that clinicians can provide patients with the basic information required to safely incorporate exercise and increased activity into their lives.

Sarcopenia and Frailty in Relation to Exercise


Sarcopenia is defined as the loss of muscle mass, strength, and function leading to adverse health outcomes [29]. Cirrhosis-induced sarcopenia affects 30–50% of end-stage liver disease patients [3033] and is most prevalent in those with advanced disease [34, 35]. As detailed in previous chapters, the pathology inherent with liver disease directly leads to impaired protein synthesis and muscle contractility as well as increased muscle breakdown. Changes in muscle mass are predictive of mortality, independent of the Model for End-Stage Liver Disease (MELD) score [34]. Evidence suggests that sarcopenia may be reversible in patients with cirrhosis after exercise rehabilitation [3640].


In cirrhosis, physical frailty is characterized by sarcopenia, malnutrition, and physical deconditioning [7]. Frailty is defined in many ways, but for cirrhosis patients, it is likely best defined as a low physiologic reserve and decreased functional status [4], which leaves patients vulnerable to health stressors, leading to physical dependency and death [41]. Roughly 20% of patients with cirrhosis are classified as frail, while 40% are functionally limited [42]. Patients are at an increased risk for falls, fractures, hospitalization, and limited recovery from health complications [42, 43]. Tests of frailty have been correlated with poor clinical outcomes in the cirrhosis population. Newly developed indices of frailty can improve the prognostic ability of conventional status scores including the Model for End-Stage Liver Disease (MELD) and Child-Pugh [42, 44]. Given that frailty in cirrhosis is characterized by declines in multiple systems, the benefits of exercise are of clinical interest to guard against health declines and to improve overall health.

Exercise Training in Cirrhosis

Rationale for Exercise Training

Physical inactivity and sedentary behaviour are strong predictors of poor health outcomes, such as cardiovascular disease, malignancy, musculoskeletal disease, and metabolic disorders [45]. In cirrhosis, physical inactivity exacerbates other existing poor health conditions, such as decreased protein synthesis, hypermetabolism, increased inflammatory cytokines, hyperammonemia, and low testosterone levels [7, 46]. Together, these factors lead to cardiovascular and skeletal muscle deconditioning, characterized by sarcopenia and frailty. Exercise improves skeletal muscle mass, strength, endurance, and cardiopulmonary function. Given that cirrhosis-related impairment is founded on muscle dysfunction and cardiopulmonary deconditioning, exercise is a promising therapy for patients living with liver disease. In other chronic disease populations, exercise-related benefits have been noted independent of the degree of physical deconditioning [47]. As the majority of studies in cirrhosis have been performed in patients with compensated disease, the degree of response expected across the strata of disease severity and physical deconditioning in cirrhosis remains to be evaluated [7, 12].

Safety Concerns

A major concern regarding exercise in cirrhosis is a rise in the hepatic venous pressure gradient (HVPG), an accurate surrogate measure of portal hypertension. Rises in the HVPG put patients at risk for variceal bleeding [48, 49]. An early study found that the HVPG increased in patients with cirrhosis and portal hypertension during exercise [49]. However, a follow-up study showed that, with the use of non-selective beta-blocker medication, a decrease in the HVPG occurs during exercise [48]. Further, evidence from more recent years has failed to prove that patients with cirrhosis and portal hypertension are at increased risk for adverse events when performing exercise [5052]. Indeed, a randomized controlled trial combining moderate aerobic and resistance exercise training resulted in decreases in the HVPG over the long term [53]. A subsequent randomized controlled trial confirmed this finding using a lifestyle intervention which involved both light-moderate exercise training and diet modification in cirrhosis patients with portal hypertension [36].

A recent meta-analysis of four randomized controlled trials performed with patients awaiting liver transplantation found that exercise programmes do not worsen Child-Pugh or Model for End-stage Liver Disease (MELD) scores [54]. Further, no adverse events occurred during these interventions. Other studies involving non-transplant wait-listed cirrhosis patients have found similar results [7]. The evidence has notable limitations, focusing largely on compensated cirrhosis patients and has included a small sample size per study [Table 7.1]. Future large-scale studies are needed to confirm that exercise is safe, particularly in decompensated patients.

Table 7.1

Exercise type and principles from the available literature on the effects of exercise on cirrhosis-related complications

Author (year)

Study design

Aetiology and Child-Pugh (n)

Intervention and cohorts (n)


Training principles

Time, frequency

(Adherence %)

Sarcopenia or frailty outcomes

Pattullo (2013)

Prospective cohort study

Hepatitis C; non-cirrhotic (n = 10), Child-Pugh A (n = 5) or B (n = 1)

Aerobic step count goals (n = 16)

12 weeks

Achieve 3000 steps/day above baseline step count, each day, light-moderate

(Adherence 100%)

↓ body weight

↓ fat mass (measured by skinfold caliper)

Debette-Gratien (2014)

Prospective cohort study

Child-Pugh A (n = 5), B (n = 1), or C (n = 2). Mean MELD = 13

Supervised aerobic and resistance exercise (n = 8)

12 weeks

Aerobic: 20+ min, 2×/week, moderate intensity

Resistance: 20 min, 2×/week, 70–80% max, 3 sets of 8–10

(Adherence “good”)

↑ VO2 peak

↑ 6MWT

↑ quadriceps muscle strength

Roman (2014)


Child-Pugh A (n = 7) or B (n = 1). Mean MELD = 9.5

Supervised aerobic and resistance exercise (n = 8) standard care (n = 9)

12 weeks

Aerobic: 10–15 min increasing to 25–30 min, 3×/week, 60–70% of max

Resistance: 5–10 min weights and 10–15 min balance/stretching, intensity based on patient tolerance, last 6 weeks of programme

(Adherence: 83.3%)

Between group:

n.s. 6MWT

n.s. thigh circumference

Within group:

↑ 6MWT

↑ thigh circumference

Macias-Rodriguez (2016)


Child-Pugh A and B (median = 6). Median MELD = 9

Supervised aerobic and resistance exercise + nutritional therapy (n = 11) nutritional therapy (n = 11)

14 weeks

Aerobic: 40 min, 3×/week, 60–80% maximum, 14 weeks

Resistance: 30 minutes, 3×/week, RPE 12–14

(Adherence: 97%)

Between group:

n.s. VO2 peak

n.s. body weight

Roman (2016)


Previously decompensated cirrhosis (mean Child-Pugh = 5.4, MELD = 8.2)

Supervised aerobic and resistance exercise (n = 14) relaxation programme (n = 9)

12 weeks

Aerobic: 10–15 min increasing to 25–30 min, 3×/week, 60–70% of max exertion

Resistance: 5–10 min weights and 10–15 min balance/stretching, intensity based on patient tolerance, last 6 weeks of programme

(Adherence: 93.6%)

Between group:

n.s. body composition (measured by dual X-ray absorptiometry)

n.s. VO2 peak

Within group:

n.s. VO2 peak

↑ muscle mass

↓ fat mass (measured by dual X-ray absorptiometry)

↓ timed up and go

Zenith (2016)


Child-Pugh A or B (mean = 6.2); mean MELD = 9.7

Supervised aerobic exercise (n = 9) standard care (n = 10)

8 weeks

30 min increasing to 50 min, 3×/week, 60–80% of max

(Adherence: not reported)

Between group:

↑ VO2peak

↑ 6MWT

↑ thigh circumference

Berzigotti (2017)

Prospective study

Child-Pugh A (n = 46) or B (≤8 pts.; n = 4)

Supervised aerobic and resistance exercise (n = 50)

16 weeks

60 minute sessions, 1×/week, RPE 10–12

(Adherence: 88%)

↓ body weight

↓ fat mass (measured by bioelectrical impedance analysis)

n.s. muscle mass (measured by dual X-ray absorptiometry)

↑ VO2 peak

Kruger et al. (2018)


Child-Pugh A (n = 14) or B (n = 6), mean MELD = 9.05

Unsupervised aerobic exercise (n = 19) standard care (n = 18)

8 weeks

30 min increasing to 60 min, 3×/week, 60–80% max,

(Adherence: 61.1%)

Between group:

n.s. VO2peak

Within group:

↑ VO2peak

↑ thigh circumference

n.s. thigh muscle thickness

Abbreviations: ↓ significant decrease (P < 0.05), ↑ significant increase (P < 0.05), n.s. non significant, 6MWT 6-minute walk test, RCT randomized controlled trial, RPE rating of perceived exertion

Effects on Sarcopenia and Frailty

Sarcopenia can be assessed by measuring muscle mass using computed tomography (CT) scan, DEXA, or ultrasound each with their inherent advantages and disadvantages. It can also be indirectly measured using bioelectrical impedance or measures of muscle strength, like handgrip strength. Although no studies have evaluated the effects of exercise on muscle mass using cross-sectional imaging (CT or MRI scans), several studies have shown improvements in both muscle mass and strength through supervised and home-based exercise training [50, 51, 5557]. Improvements in muscle mass can also be complemented by decreases in fat mass [36, 52, 56, 58].

Cardiopulmonary endurance/function is often assessed by either cardiopulmonary exercise testing or the 6-minute walk test. Frailty can be assessed by composite tests, including the Short Physical Performance Battery (comprised of gait speed, balance, and repeated sit to stand) or the Liver Frailty Index (including balance, repeated sit to stand, and handgrip strength tests). Trials in cirrhosis have shown that exercise training can reduce the risk of falls [56], decrease fatigue [50], and improve exercise capacity as well as physiologic reserve [36, 5053, 55, 56]. Further research is required to explore the effects of exercise training on additional frailty metrics.

Although the evidence supports the use of exercise training to attenuate sarcopenia and frailty in patients with liver disease, there is much variability in the frequency, intensity, time, and type of exercise showing effects in the literature. Trials have ranged from progressive step goals for aerobic exercise to supervised randomized controlled trials using both aerobic and resistance exercise [Table 7.1]. The exercise parameters vary considerably, yet it is clear that both resistance and aerobic exercise show promise in targeting sarcopenia and frailty in this population.

Pre-exercise Screening and Assessment

There are several recommended pre-exercise health safety screens that should be performed before initiating an exercise programme. As described by Tandon et al., pre-exercise screening can be divided into three categories: cirrhosis-related safety considerations, cardiopulmonary safety screening, and other considerations [12].

Cirrhosis-Related Safety Considerations

The 2015 Baveno VI Consensus recommends that patients with a FibroScan score ≥20 kPa or platelet count ≤150,000/μl be screened for varices [59]. Thrombocytopenia (low platelet count) is not a contraindication to exercise per se, but exercises with high risk of injury or falling should be avoided, particularly when platelets are <20,000/μl. In this situation, it is recommended that the patient is prescribed exercises that incorporate a stable support surface. Patients with high-risk varices or those who have had a previous variceal bleed should be on primary or secondary variceal prophylaxis prior to exercise initiation [60].

Beyond varices, no other cirrhosis-related considerations are absolute contraindications to activity that is low-moderate intensity. However, a number of other complications can impact exercise tolerability, adherence, and efficacy [2]. These include large volume ascites, pedal oedema, and hepatic encephalopathy. Patients with ascites typically experience impaired exercise capacity, and it may be challenging to perform certain exercises. Exercises should be progressed on days where ascites accumulation is minimal. Exercises where pressure is put on the abdomen (i.e. prone exercise or straining abdominal exercises) should be avoided. For patients with overt hepatic encephalopathy, their readiness to engage, understand, and perform exercise directions should be considered. At the very least, a caregiver should be present during exercise sessions. Finally, patients on diuretic therapy may be at risk of volume depletion or hypotension following exercise. These patients should consume water during their exercise sessions, monitor symptoms of dizziness [61], and end the exercise session immediately if they feel faint.

Cardiopulmonary Safety Screening

Prevalence of cardiovascular risk factors in the liver disease population is high, but the link between these factors and events is low. The current American College of Sports Medicine (ACSM) guidelines recommends “medical clearance” for those starting a moderate intensity programme with signs, symptoms, or a history of cardiovascular, metabolic, or renal disease. Medical clearance should be obtained if the patient presents with any of the following signs or symptoms: chest discomfort with exertion, unreasonable breathlessness, dizziness, fainting, blackouts, heart palpitations, lower limb claudication, or heart murmur [62]. Likewise, medical clearance should be obtained if the patient has a history of the following: heart attack, heart surgery, cardiac catheterization or coronary angioplasty, pacemaker, heart valve disease, heart failure, heart transplantation, congenital heart disease, diabetes, or renal disease. The procedure for medical clearance is left up to the clinician.

ACSM defines moderate intensity as 40–59% heart rate reserve, a VO2 reserve of 3.0–5.9 metabolic equivalent (METs), or a rating of perceived exertion (RPE) of 12–13 on the 6–20 Borg scale or 5–6 on the 0–10 scale.

In our opinions, asymptomatic patients wanting to pursue low-moderate activity should adhere to a “start low and progress slow” approach to training [7] and do not require a pre-participation cardiac clearance [63]. In symptomatic patients, it may be beneficial to conduct additional testing, including cardiopulmonary exercise testing. At the very least, approval for participation should be obtained from the patient’s clinician prior to exercise training initiation.

Other Safety Considerations

Patients should be asked if they experience exertional symptoms that limit their activities of daily living. This can help identify factors (e.g. muscle cramping, claudication, joint pain, restricted range of motion) that may require exercise programme modification or additional therapeutic intervention before exercise initiation [19]. During physical performance assessments, fall risk can be assessed using balance testing included in the Short Performance Physical Battery or Liver Frailty Index . Those at high risk of falling should perform supported activity (e.g. seated or standing with a support). Caregiver supervision is also recommended. If the patient has additional comorbidities, the recent ACSM guidelines should be consulted for safety implications [19]. Lastly, for patients who are identified as having an increased risk of falling, careful consideration is needed before progressing the patient to unsupported exercises.

Exercise Prescription

Encourage Non-exercise Activity Thermogenesis (NEAT)

Describing the simple principles of NEAT to patients is a way to encourage them to increase the amount of physical activity that they do outside of scheduled exercise programming. NEAT activities involve making the “less convenient” choice, with a goal to increase activity, for example, stepping in place while watching TV instead of sitting on the couch, climbing stairs instead of taking the elevator, or parking in a spot further away from their destination instead of the closest spot [64].

Scheduled Exercise Programming

On the basis of the available literature, 30- to 60-minute sessions of both aerobic and resistance training are recommended with the goal being to achieve 150+ minutes/week of moderate intensity exercise. For an exercise training programme to be effective, it should last at least 3 months to facilitate physiological gains [65]. Resistance exercise should always be prescribed as it has an important role in preventing or attenuating muscle loss. Aerobic exercise compounds the effects of resistance exercise by improving physiological reserve and functioning of patients. Flexibility and balance exercise can complement these two primary training modes by maintaining joint function and balance. Table 7.2 outlines the ideal frequency, intensity, time (duration), and type of exercise that are effective in targeting sarcopenia and frailty and explain how exercise can be progressed for patients with liver disease. These recommendations are adapted from Tandon et al. [12].
Aug 3, 2021 | Posted by in GASTROENTEROLOGY | Comments Off on Training in Patients with Cirrhosis
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