Hepatic Cirrhosis and Physical Activity: A Guide for the Clinical Practice

Diane Michela Nery Henrique1, Carla Malaguti2, Carlos Alberto Mourao-Junior3, Daniel Godoy Martinez4, Fabio Heleno de Lima Pace3, Giovanna Pereira Neiva Boechat da Rocha3, Mateus Camaroti Laterza4, Tarsila Campanha da Rocha Ribeiro3, Tuany Mageste Limongi4, Cristiane de Souza Bechara3, Julio Maria Fonseca Chebli3

1 Department of Medicine, University Hospital, Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil;
2 Physiotherapy Department, Federal University of Juiz de Fora, University of Juiz de Fora School of Physiotherapy, Minas Gerais, Brazil;
3 Division of Gastroenterology, Department of Medicine, University Hospital, Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil;
4 Cardiovascular Research Unit and Exercise Physiology, University Hospital and Faculty of Physical Education and Sports, Federal University of Juiz de Fora, Juiz de Fora, MG.

Conflict-of-interest statement: The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.

Open-Access: 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/

Correspondence to: Julio Maria Fonseca Chebli, Division of Gastroenterology, Department of Medicine, University Hospital, Federal University of Juiz de Fora, University of Juiz de Fora School of Medicine, Minas Gerais, Brazil.
Telephone: +55 (32) 2102-3841
Email: chebli@globo.com

Received: December 2, 2021
Revised: December 28, 2021
Accepted: Jaunary 1, 2022
Published online: February 21, 2022


Patients with liver cirrhosis have impaired physical fitness involving several multifactorial mechanisms, such as sarcopenia, hyperdynamic circulatory status, and hepatopulmonary syndrome, in addition to sedentary behavior. The reduction in exercise tolerance is related to the degree of impairment of liver function in these patients. Therefore, the assessment of exercise capacity has been shown to be valid as a measure of prognostic value and to predict the clinical risk of decompensation. This review briefly shows the importance of evaluating exercise functional capacity in cirrhotic patients, as well as highlights how exercise and physical activity programs are safe and effective in improving muscle mass, increasing exercise capacity, and reducing the pressure gradient hepatic venous. It is expected that the assessment of the functional physical status of cirrhotic patients and their encouragement to engage in exercise programs and increased physical activity will be encouraged in clinical practice.

Key words: Hepatic cirrhosis; Physical activity; Clinical practice

© 2022 The Author(s). Published by ACT Publishing Group Ltd. All rights reserved.

Henrique DMN, Malaguti C, Mourao-Junior CA, Martinez DG, de Lima Pace FH, da Rocha GPNB, Laterza MC, da Rocha Ribeiro TC, Limongi TM, de Souza Bechara C, Chebli JMF. Hepatic Cirrhosis and Physical Activity: A Guide for the Clinical Practice. Journal of Gastroenterology and Hepatology Research 2022; 11(1): 3652-3657 Available from: URL: http://www.ghrnet.org/index.php/joghr/article/view/3261


Liver cirrhosis is a prevalent disease that currently ranks among the leading causes of global mortality, and 2.4 % of all deaths in the world occurred due to its complications in 2017[1]. Chronic hepatitis B and C, alcoholic liver disease, and fatty liver disease associated with metabolic dysfunction (MAFLD) are the most common etiologies[1], the latter of increasing incidence.

Different agents and mechanisms can cause chronic and insidious aggression by inflammation, cell necrosis, and activation of hepatic fibrogenesis responsible for the synthesis of extracellular matrix, being hepatic stellar cells a key element in this process. Furthermore, with the progressive deposition of collagen matrix in the liver parenchyma, there is the formation of fibrotic nodules and distortion of the vascular architecture that results in the loss of the organ’s functional capacity and the development of portal hypertension, ultimately responsible for the morbidity and mortality observed in this group of patients[2,3].

Currently, among the complications of chronic liver disease, such as ascites, hepatic encephalopathy, and variceal bleeding, sarcopenia and frailty have been highlighted. These are interrelated conditions, with sarcopenia being defined as a reduction in muscle volume and strength and frailty as a condition in which there is a low physiological reserve and high vulnerability to health stressors [4]. Sarcopenia is a common finding among the elderly and is present in several chronic diseases, but individuals with chronic liver disease are especially predisposed[5]. In patients with liver cirrhosis, sarcopenia contributes to both the reduction in physical performance and exercise capacity, which are related to adverse outcomes[4].

Common conditions within the spectrum of chronic diseases, and present in liver fibrosis, such as malnutrition, persistent chronic inflammatory state, changes in metabolism, and sedentary lifestyle are added to cause a reduction in the ability to carry out physical activities and exercises per contributing to the impairment of peripheral muscles[6]. Furthermore, systemic disturbances can affect the heart, lungs, kidneys, and other organ systems in chronic liver disease[7]. Therefore, the impairment of physical fitness is multifactorial in these patients involving several mechanisms as sarcopenia[6], the hyperdynamic circulatory state[8], and hepatopulmonary syndrome[9].

Assessment of functional capacity in cirrhotic patients

Since physical fitness is a broad and complex concept, the ability of the heart and lungs to meet the metabolic demand of skeletal muscles is used to assess an individual’s exercise capacity and functionality. The capacity for aerobic exercise, that is, the use of oxygen during the physical effort and the functional capacity to perform activities of daily living, are aspects of physical condition that can be evaluated through specific and validated tests[10]. The most common tests used in the cirrhotic population are the cardiopulmonary exercise test (CPET) and the six-minute walk test (6MWT)[6].

CPET is considered the gold standard for addressing exercise capacity by measuring a series of variables related to the body’s ability to capture, transport, and use oxygen[11,12]. In the CPET, an exercise is performed on a treadmill or cycle ergometer, gradually increasing intensity until exhaustion or the appearance of limiting signs and symptoms. During exercise, clinical signs and symptoms, heart rate (HR), electrocardiogram, and blood pressure (BP) are monitored. In addition, respiration is evaluated through a gas analyzer, allowing the measurement of ventilation, oxygen consumption, and carbon dioxide production[13]. Usually, in this approach, the measurement of the peak of oxygen uptake (Peak VO2) and the first ventilatory threshold, also known as the anaerobic threshold (AT), stand out. The Peak VO2 value corresponds to the maximum load of effort tolerated by the individual. Thus, it is, at least partially, influenced by the effort of the tested patient to perform this effort. Conversely, the AT corresponds to the graphic manifestation of the beginning of the change from aerobic to anaerobic metabolism and is a submaximal measure that does not depend on the individual’s effort to perform a maximum test[11].

The 6MWT is a technically less complex assessment, performed in a flat 30-meter stretch of an unimpeded walkway. Monitoring of clinical signs and symptoms, BP, HR, and oxygen saturation is effectuated through a pulse oximeter during the six minutes that the patient walks at the fastest possible pace, but without running, according to his physical condition. Standardized instructions are given before starting the test, and verbal feedback is given every minute, as recommended by the American Thoracic Society guidelines. At the end of six minutes, the total distance walked is calculated due to the test[14]. The 6MWT is a submaximal exercise test that has been shown to have good reliability when used to assess the functional capacity of cirrhotic patients[15], in addition to correlating with the functional capacity assessed by CPET[16,17]. In addition, the 6MWT has the advantages of being easy to be operated by the examiner, has low cost, and presents minimal risk to the patient. Therefore, it is a valid alternative for the evaluation of cirrhotic patients in any scenario.

Previous studies have shown that patients with cirrhosis have a 40% to 50% reduction in oxygen consumption than their healthy sedentary peers[16,18]. In addition, these patients showed a reduction in exercise tolerance, which is associated with the degree of liver function impairment[15,18,19].

Clinical implications of reduced functional capacity in cirrhosis

Several studies with cirrhotic patients point toward a direct relationship between physical fitness and prognosis[17,20], following the line of studies that demonstrated that low physical fitness is associated with more significant morbidity and mortality from all causes in the presence of various chronic diseases. Furthermore, over the past few years, studies have shown that the assessment of functional capacity in cirrhotic patients presents itself as a valuable tool to assess survival[15,17], the prognosis before and after liver transplantation[11-12,21-21], and, more recently, the risk of clinical decompensation[20].

Alameri and colleagues[15] showed that the distance covered in the 6MWT by patients with chronic liver disease was shorter than that covered by healthy individuals. Furthermore, this distance was even shorter when patients were already in the stage of established cirrhosis. The 98 cirrhotic patients in this study were followed up on an average follow-up of 42 weeks (SD ± 13 weeks), and 15% of them died from complications of liver disease during this follow-up period. The Kaplan-Meier survival curve was used to evaluate these patients in terms of distance walked on the 6MWT, and the log-rank test demonstrated that cirrhotic patients who walked less than 250 m had a lower survival (P: 0.021). Thus, the authors identified this tool as capable of producing an additional prognostic marker in patients with liver cirrhosis, as it was an independent predictor of survival in this group of patients.

Carey et al. linked the distance walked on the 6MWT with survival in liver transplant candidates with MELD score above 15, at a mean follow-up time of 148 days[21]. This study showed that 6MWT distance was significantly associated with mortality. A distance below 250 m was a predictor of increased risk of death for those cirrhotic patients on the waiting list for the procedure. In particular, a 52% reduction in mortality was noted for every 100 m increase in baseline 6MWT [HR 0.48, 95% CI: 0.33-0.67, p < 0.0001 for every 100 m increase in distance walked]. Distance on the 6MWT was an independent predictor of mortality in transplant candidates, even after adjustments for age and MELD score, and could identify candidates at higher risk of death on the waiting list.

A study published by Bernal et al. evaluated the relationship between aerobic fitness parameters, determined by CPET performed by elective indication in the preoperative period of liver transplantation, and 1-year mortality after CPET for patients not undergoing transplantation during this period and also the 1-year mortality after transplant in those submitted to the procedure[11]. This study included 399 cirrhotic patients referred for transplantation, although some of them were declined from the procedure according to the assessment of the clinical staff of the referral hospital. The CPET parameters considered were Peak VO2 and AT. The authors demonstrated a clear relationship between aerobic fitness and survival in patients who underwent and those who did not undergo liver transplantation within a one-year follow-up. Additionally, the AT’s superiority was found compared to the Peak VO2 to predict mortality, although without establishing an exact value of the AT to discriminate survivors from non-survivors.

Ow et al. examined the association between maximal exercise capacity and survival in transplant waiting list patients also found the potential of CPET in predicting 90-day free-transplant mortality[22]. The Peak VO2 was significantly lower among non-survivors (15.2 versus 21.2 mL/min.min-1; p < 0.001). Peak VO2 had a good performance for this sample with an area under the curve of 0.84 (95% CI, 0.76-0.92, sensitivity: 90%, specificity: 74%; p < 0.001). The cutoff value established to predict mortality was < 17.6 mL/minute.kg-1. The authors concluded that patients evaluated for liver transplantation with greater impairment of functional capacity have a lower short-term survival rate; this is particularly true for individuals with more severe liver disease.

In the same line of investigation, patients with chronic liver disease who were potential candidates for liver transplantation underwent CPET and 6MWT[9]. An evaluation of the three-year survival curve showed that patients with values ​​below 17 ml/kg/min had a survival rate of 55% compared with 94% survival for those who reached values ​​> 17 ml/kg/min on the CPET. In addition, individuals who walked less than 410 m on the 6MWT had a lower survival rate (55%) compared to the 97% survival rate of those who walked more than that. Thus, in this study, the distance walked on the 6MWT and the Peak VO2 were independent predictors of mortality.

In a systematic review on the subject [12], researchers collected data to better establish the predictive value of CPET as a tool to assess maximal exercise capacity in cirrhotic patients before and after liver transplantation. Five studies focused on the Peak VO2 and TA, two studies only on Peak VO2, and a single study evaluated the oscillation curve of ventilation during exercise. The researchers found that the studies support CPET as an objective and independent predictor of pre-and post-transplant mortality. However, some drawbacks of this review need to be pointed out as the heterogenicity of included studies, different CPET parameters, CPET cutoff values, and follow-up time, not making it possible to satisfactorily identify specific cutoff values ​​related to pre-and post-transplant mortality based on the analyzed data.

More recently, our research group dedicated itself to investigating the relationship between functional capacity and clinical decompensation in cirrhotic patients[20] (19). Since the primary determinant of survival in patients with cirrhosis is the development of decompensation[23], we decided to investigate the ability of the 6MWT as a predictor of the risk of clinical decompensation (i.e., jaundice, ascites, bleeding from esophageal varices, spontaneous bacterial peritonitis or hepatic encephalopathy) in clinically compensated cirrhotic patients. Therefore, a cohort of 55 cirrhotic patients was followed up for 12 months (mean age 56.3 years, 65% male, 65% Child-Pugh class A and 35% Child-Pugh class B) after the 6MWT. In the studied sample, the 6MWT predicted the highest risk of developing clinical decompensation of cirrhosis in the one-year follow-up for those patients who walked less than 401.8 meters (sensitivity of 64% and specificity of 82%). In addition, we also found data indicating that, at one-year follow-up, worse performance on the 6MWT was able to predict a greater need for hospitalization due to clinical decompensation of the disease.

Finally, the currently published literature supports the importance of assessing functional capacity in the clinical follow-up of cirrhotic patients and raises the question of the value of recommending regular physical activity for these individuals to improve patients’ physical fitness and, consequently, the prognosis.

Physical activity and liver cirrhosis

Several health associations have indicated the regular practice of physical exercise as a non-pharmacological strategy for preventing and treating chronic diseases. This clinical approach even has a positive impact on reducing the probability of death. In a study carried out in the United States of America, with almost 480 thousand North Americans followed for nine years, the practice of aerobic, resistance, or both physical exercises reduce, on average, up to 0.60 the risk relative of all-cause mortality[24].

Exercise programs ranging from 8-14 weeks in duration have showed improvements in peak exercise capacity, muscle mass, muscle strength, quality of life and fatigue[25]. Ideally, all patients with decompensated cirrhosis should receive pre-exercise safety evaluation and an exercise instruction as suggested in Table 1. Usually, resistance training is the target of many exercise programs in patients with decompensated cirrhosis, with aerobic training introduced subsequent. If falls are a concern issue, initial priority is often placed on lower extremity strength and balance training[25].

Table 1 Pre-exercise safety evaluation and exercise schedule suggested for cirrhotic patients Pre-exercise safety assessment.
Cirrhosis related safety screeningHigh-risk varices: prophylaxis needs
Hepatic encephalopathy, ascites: optimize supervision by caregivers
Assess physiological competenceAssess for fall risk, musculoskeletal limitations
Cardiopulmonary safety screening
Exercise Prescription - FITT * Recommendations
FrequencyAerobic: 4-7 d/week;
Resistance: 2-3 d/week;
Flexibility and balance: 2-3 d/week
IntensityBorg scale: moderate intensity 3-5/10
Talk test: able to speak in full sentences but stil?notices laboured breath
Type Aerobic: build to 150 minutes per week. The very?deconditioned may need to start with 1-min of walking followed by 1-min of rest.
Resistance: 3 sets of 10-15 repetitions.
Flexibility and balance: 1 set of 3 repetitions
TimeAerobic: walking is the most universal aerobic intervention
Resistance: functional (e.g. stairs) or progressive weight/band training
Flexibility and balance: stretching and balance exercises
* FITT (Frequency, Intensity, Type, Time); Adapted from Tandon P et al. J Hepatol. 2021; 75 Suppl 1:S147-S162. [25]

In a study developed by Bacchi E., patients with nonalcoholic fatty liver disease and type 2 diabetes were randomized for moderate-intensity aerobic exercise training or resistance exercise training. After a 4-month period, the groups similarly decreased body mass index, glycated hemoglobin levels, and liver fat content. Additionally, it was possible to note that hepatic steatosis, defined as hepatic fat content greater than 5.56%, disappeared in approximately 25% of people[26]. Likewise, in a cross-sectional analysis of a representative sample of the North American population, it was shown that people who followed the national recommendations for the practice of physical activities had a lower chance of developing nonalcoholic fatty liver disease. Indeed, people who performed more than 300 minutes of weekly physical activity had a 63% reduced risk of developing liver cirrhosis[27]. These findings allow us to infer that a physically active lifestyle can prevent or at least attenuate risk factors for the development of liver cirrhosis.

Regarding the management of people with liver cirrhosis, physical training has been receiving critical attention. After only eight weeks of supervised aerobic physical training of moderate-intensity, cirrhotic patients, classified as Child-Pug A and B, increased the VO2 peak, the distance covered in the 6MWT, the thigh circumference, and decreased the fatigue index. Even without modifying the biochemical parameters, no adverse effects were reported throughout the physical training protocol[28]. However, it is noteworthy that in this study, the patients were stable, underwent cardiopulmonary testing, and, when necessary, underwent primary prophylaxis to prevent bleeding from esophageal varices. Moreover, Román et al. demonstrated that 12 weeks of aerobic exercise training associated with resistance was effective in increasing lean mass and decreasing fat mass of patients with liver cirrhosis evaluated by body composition through dual-energy X-ray absorptiometry, contributing to justify, at least in part, the observed decrease in the risk of falling in these patients[29].

In association with improved functional capacity and body composition, physical training can also change hepatic hemodynamics. After 14 weeks of supervised aerobic physical training of moderate-intensity, associated with muscle strengthening, coordination, and balance exercises, stable patients with liver cirrhosis had an average decrease in the hepatic venous pressure gradient by 2.5 mmHg, a fact that was not observed in the control group. In this study, all patients were evaluated and monitored from a cardiological and hepatic point of view. No episode of variceal bleeding or hepatic encephalopathy was recorded during this follow-up [30]. Also, regarding portal pressure, a 16-week intervention for lifestyle modification, consisting of a low-calorie diet associated with moderate-intensity aerobic exercise training, was effective in decreasing at least 10% of the hepatic venous pressure gradient in 42% of patients. A decrease of at least 20% in this gradient was observed in 24% of patients with liver cirrhosis and portal hypertension[31].

As the functional capacity is directly associated with the severity of the liver disease, patients with liver cirrhosis with an indication for liver transplantation have a significant deficit in the functional capacity. And, as in other chronic conditions, the prescription of physical exercise seems to be an exciting approach for people on the waiting list for a liver transplant. A study developed by Morkane et al. demonstrated the excellent feasibility of a physical exercise program for patients with liver cirrhosis on the transplant waiting list. In this prospective cohort, patients significantly improved their functional capacity, expressed as an increase in peak VO2, after six weeks of the proposed aerobic exercise training program. However, 44% of patients could not complete the intervention period, none of the cases linked to exercise. In addition, no adverse events related to physical training were reported[32].

Through these findings, it is possible to suggest that physical exercise should be the approach adopted in the prevention and treatment of chronic liver diseases. For safety, we suggest a careful and multidisciplinary evaluation to include patients in supervised physical training programs.


Patients with liver cirrhosis have a multifactorial reduction in exercise tolerance, and this impairment is related to the prognosis of the disease. According to this, it seems reasonable to seek access to the functional capacity of these patients as a complementary method of the clinical assessment in liver cirrhosis. For this evaluation, the CPET and the 6MWT are two already validated tools in this population. Furthermore, to offer a safe, tolerable and effective rehabilitation program to this population, it is crucial to understand several points as the clinical pathophysiology of exercise in this health condition, systemic repercussions of exertion, and potential risks and benefits of physical activity exercise. Finally, although there are barriers to the practice of physical exercise in patients with liver cirrhosis, there is the current knowledge of its effectiveness and safeness. Likewise, it is up to the practicing clinician to encourage and direct their patients to exercise under the supervision of a multidisciplinary team.


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