For nearly 20 years, there has not been sufficient information in the medical literature for supporting and recommending physical exercise as a useful intervention in patients with cirrhosis of the liver and portal hypertension. The evidence for not recommending exercise in cirrhosis was based on findings from 2 studies with small samples. In the first, an acute increase in the hepatic venous pressure gradient (HVPG) was found in patients while they exercised on a cycle ergometer.1 The second study produced the same finding of increased HVPG, which was prevented in the group that received a beta-blocker before exercising. Given that evidence, exercise was not considered recommendable in patients with cirrhosis due to the potential risk for inducing variceal bleeding.2

One of the most important observations in those 2 studies was that the increase in the HVPG was acute, occurring while the patient was exercising on the cycle ergometer. That response was similar to the normal physiologic increase in systemic blood pressure observed in healthy patients while they exercised.3,4 It could thus be supposed that the increase in portal pressure during exercise was a normal physiologic response that could be modified under specific circumstances, such as a physical training program. The adaptation by the body, and specifically certain organs, to exercise has been documented in cardiopulmonary diseases, such as heart failure, chronic obstructive pulmonary disease, and post-acute myocardial infarction.5,6

The initial evidence showing that physical exercise was safe for cirrhotic patients with portal hypertension came from a small randomized controlled study in which the effect of supervised aerobic exercise was evaluated. It found that chronic exercise did not increase the HVPG, but actually lowered it.7 Similar results were reported in a subsequent non-controlled study in patients with cirrhosis due to NAFLD.8 Exercise has numerous potential benefits beyond its safety in terms of portal pressure (and even better, the decrease in HVPG), making it a very attractive intervention considered first-line treatment in patients with cirrhosis and portal hypertension. Those benefits include improvement in cardiopulmonary and metabolic function, in body composition, and in quality of life.7,9,10

Despite the abovementioned benefits of exercise, at present there are no guidelines or recommendations on exercise prescription in cirrhosis, the limiting factors that should be considered before initiating an exercise program, intervention follow-up, and the importance of concomitant nutritional therapy. The aim of the present review is to provide information that serves as a guide for the care of patients with cirrhosis that are undergoing an exercise program.

To understand the importance of exercise in cirrhosis, some basic definitions need to be understood, before the evaluation and prescription of an intervention in patients. Even though definitions vary, depending on the organization they come from (fig. 1), and are derived from non-cirrhotic populations,11 the final aim of any exercise program should focus on 3 main points: a) to maintain functionality while the patient is receiving drug treatment or is waiting for definitive treatment (OLT), b) to achieve and maintain the independence of the patients, and c) to improve quality of life. When the body of the patient is “functional”, it allows him/her to maintain a minimum level of functionality, enabling the use of the different bodily systems (central nervous system, muscle system, cardiopulmonary system) to carry out the basic necessities in daily life, when not completely bedridden.

Figure 1.

Interrelation between physical activity, exercise, and physical fitness Taken from Caspersen CJ, Powell KE, Christenson GM. Public Health Rep. 1985;100(2):126–31.

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A functional patient is independent and satisfies the basic needs of daily life, including cooking, bathing alone, walking unassisted, etc. Finally, the integration of functionality and independence enables the patient to interact with others and limits comorbidities and costs related to the disease, signifying a better quality of life (fig. 2).

Figure 2.

Effect and evaluation of the interrelation between physical activity, exercise, and physical fitness. There is a close relation between physical activity, exercise, and physical fitness that constitutes a continuum with an impact on multiple systems of the organism, with the cardiovascular, respiratory, muscle, and neurologic systems among the most important. That effect is usually evaluated through the response to cardiopulmonary stress, utilizing different methods, such as the cardiopulmonary exercise test and the 6min walk test. Finally, maximum oxygen intake (VO2max) is the most widely studied objective parameter in relation to physical fitness.

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The integration of all those concepts aids in becoming aware of the importance of physical activity in the patients with cirrhosis, in the planning and tailoring of the exercise program, and finally, in visualizing the ultimate goal for the patients, centering the program on that aim.

When a patient with cirrhosis is evaluated for the purpose of undergoing an exercise program, one of the basic questions is how to follow the changes in the variables that indicate physical aptitude, considering the resources available in the center in which the patient is evaluated, and to know the limits and benefits of each method. Follow-up is an obligatory step after beginning any intervention related to exercise in patients with cirrhosis, and 2 objectives must be considered: 1) monitoring the patients while they are exercising, and 2) evaluating the final effect of the exercise on physical aptitude and physical fitness.

Physical activity can be monitored in patients with cirrhosis both in the hospital or in an outpatient setting. The majority of information on that population comes from supervised programs (in-hospital), in which there was direct supervision by a trained team (nurses, physicians, physical therapists). Some of those approaches include the monitoring of heart rate (HR) during exercise, with the goal of reaching 60-70% of the maximum HR (HRmax=220−age, among other formulas that could be more exact, such as HRmax=207−[0.7 x age]).12,13 Other methods for monitoring physical activity in those patients are direct supervision by a specialist in physical activity/rehabilitation that guides the exercise, but without an objective method to measure aspects such as HR, metabolic equivalents (METs), etc.

Even though there are recent guidelines on exercise prescription in healthy adults, as well as on those with different diseases (the American College of Sports Medicine [ACSM]), they are not designed for the care of patients with cirrhosis. There are still no studies on the cirrhotic population that evaluate the general prescription model of the ACSM, which shall be described further ahead.

However, the most important and difficult challenge is the outpatient monitoring of exercise in patients with cirrhosis. There are methods, such as a pedometer, that are simple, accurate, and fairly inexpensive for achieving that. The most practical manner to measure the daily physical activity in cirrhotics is counting the number of steps with a wrist accelerometer, which estimates both the number of steps (like a pedometer) and the physical activity in METs. Habitually, the mean number of daily steps are monitored for a period of 2-3 weeks,14 but reliable information is obtained through a 3-day register (2 days during the week and 1 day at the end of the week).15 Tudor-Locke et al. proposed the following classification of physical activity evaluated by pedometer in non-cirrhotic adults:16a) sedentary <5,000 steps/day; b) low activity 5,000-7,499 steps/day; c) moderate activity 7,500-9,999 steps/day; and d) active ≥ 10,000 steps/day. Those values contrast considerably with that reported in patients on the waiting list for ORT (3,164±2,842 steps/day vs 7,000–14,000 in healthy, non-cirrhotic adults), in which a negative correlation between the severity of the disease and the number of daily steps can be seen.17 Nevertheless, there is currently no consensus that defines the degree of activity according to the number of steps in the population with cirrhosis, making the abovementioned classifications inapplicable to those patients.

The Karnofsky index and Rosow-Breslau questionnaire are among the different subjective scales for evaluating the capacity of patients to perform daily life activities. It is important to mention that the results of those scales are not associated with real physical performance, when compared with other more reliable tools, such as step measurement with a pedometer, but they can be useful when no other instruments are available. The most important limitation of subjective scales is probably that patients perceive they are more active than they really are. Therefore, objective monitoring of physical activity with instruments that can measure the number of steps is of special interest in cirrhosis.18

It is important to know how many steps a patient takes daily and thus design clinical interventions that increase their number. In a previous study, an intervention utilizing a branched-chain amino acid (BCAA) supplement, plus an average of 2,000 steps daily, was evaluated. After 3 months, leg strength measured by ergometer and grip strength improved significantly.19 In patients with heart disease, the pedometer has been reported to serve as a self-motivation tool because of the information it provides, leading to greater competence for achieving the daily step goal.20

The 6-minute walk test (6 MWT) is a commonly used method for evaluating cardiopulmonary fitness in patients with pulmonary, neuromuscular, and neurologic diseases. It is reported to be useful for patients with cirrhosis, as well as in hospitalized patients with hepatocellular carcinoma. The parameter of cardiopulmonary fitness is generally used in clinical trials to quantify the changes resulting from an exercise intervention, to improve aerobic capacity.21,22 The 6 MWT is a practical test that measures the distance a patient can quickly walk on a flat surface in 6min. It evaluates the responses of all the systems involved during exercise, including the pulmonary and cardiovascular system, systemic and peripheral circulation, and muscle metabolism.23 The guidelines established by the American Thoracic Society for performing the 6 MWT recommend using a 30 m long corridor with a flat surface, but not all centers have such long hallways, hindering its application. Therefore, the use of 20 m long corridors has been validated for the performance of said test in patients with cirrhosis.24

In addition to being easy to use, the 6 MWT is inexpensive. It is utilized to evaluate therapies and rehabilitation programs, and as a mortality predictor in candidates for liver transplantation. In fact, patients that walk less than 250 m have a higher mortality rate than those that walk more than 350 m. The respiratory symptoms associated with the test are also correlated with reduced lung capacity, which is a predictive strategy for hospital stay duration and mechanical ventilation after a transplant.25,26 Besides the prognostic importance of the 6 MWT, it is useful for monitoring the effect of different exercise programs in patients with cirrhosis.27,28

Another useful method for evaluating cardiopulmonary fitness is the cardiopulmonary exercise test. It is generally performed on a motorized treadmill or on a cycle ergometer. Cycle ergometry is the most widely used, because it is appropriate for patients with gait instability, orthopedic limitations, or severe obesity.29 Respiratory gas exchange is measured through oxygen consumption (VO2) and carbon dioxide elimination (VCO2), through which maximal oxygen consumption (VO2max) can be calculated. VO2max is the most widely used parameter for evaluating cardiopulmonary fitness and indicates when the actual physiologic limit is reached. That differs from peak oxygen consumption (VO2peak), which is observed when the maximal performance is limited by local muscle factors, and it is used in persons with chronic diseases. Thus, VO2peak would be recommended in patients with cirrhosis.22

To evaluate cardiopulmonary capacity in patients with cirrhosis, the majority of whom perform very little physical activity, it is important to select an appropriate test protocol. Those that maintain the work rate, or gradually and lightly increase it, are recommended. Ideally, the selected protocol should allow the patient to reach an 8-12min period of fatigue-limited exercise. It should be selected according to the comorbidities of the patient and the complications of the cirrhosis.29 On the other hand, if a concomitant evaluation of heart disease (which can be important in patients with NAFLD) is necessary, patients should reach maximum exertion during the test. Nevertheless, there are currently no studies that evaluate which is the best protocol for patients with cirrhosis.13

Before assigning a patient to a physical exercise program, a thorough medical examination of his/her general state of health must be performed that includes evaluating cardiopulmonary function, concomitant diseases, and musculoskeletal limitations. The primary aim of the evaluation in the non-cirrhotic population is to identify any datum (medical condition, sign or symptom) that constitutes a potential risk in relation to the safe participation in an exercise program.13

With that in mind, in the first clinical evaluation for exercise prescription in patients with cirrhosis, the treating physician should focus on 2 areas: 1) the examination of any condition that could keep the patient from safely doing exercise, taking into account the guidelines recommended for the general population (i.e., cardiovascular disease, musculoskeletal disorders, metabolic disease, and kidney disease), and 2) specific complications of cirrhosis.

Regarding exercise prescription, the ACSM guidelines recommend a medical evaluation in patients presenting with cardiovascular, kidney, or metabolic diseases or their signs and symptoms. Even though there are no specific recommendations for patients with cirrhosis, it is logical to suggest that all patients should be evaluated by an experienced physician (with respect to clinical judgement) to identify risk conditions such as those described above, before they begin exercising. Considering that the majority of patients with cirrhosis do not regularly perform physical activity (i.e., 30min of moderate physical activity, 3 times/week over the past 3 months) and the possible coexistence of cardiovascular, metabolic (e.g., in NAFLD), or kidney (kidney dysfunction due to diuretics, hepatorenal syndrome) involvement, all patients with cirrhosis should undergo a thorough medical evaluation.13,30

To achieve an adequate risk evaluation for patients to be assigned to an exercise program, in addition to a complete medical examination, laboratory tests and imaging studies that could help better characterize their general state of health should be considered. Among those tests and studies are lipid profile, fasting glucose, glycosylated hemoglobin, C-reactive protein, electrocardiogram, echocardiogram, spirometry, blood cytology, and chest x-ray. There are specific guidelines that give a detailed description of the usefulness of each of those exams, but in general it can be stated that a thorough clinical evaluation and common sense will dictate which studies should be carried out, including the specialized studies for evaluating cardiac reserve and coronary artery permeability, if they are indicated by risk factors (electrocardiogram, catheterization, thallium-201, or technetium 99m-sestamibi, etc.).31

Validated questionnaires are a good option among the different tools for the initial approach to the state of health and physical activity in patients whose goal is to begin an exercise program. Those questionnaires have been developed by different international organizations, including the Canadian Society of Exercise Physiology, the World Health Organization, the ACSM, and the American Heart Association (Table 1). The use of the PAR-Q+questionnaire is advisable, given that it has been widely validated and is recommended in the latest ACSM Guidelines for Exercise Testing and Prescription (ACSM 10).

In general, cirrhotic patients are less active than non-cirrhotics, and the majority of clinical trials on exercise in cirrhosis have been supervised.7,28,32 There are specific complications of cirrhosis that limit the performance of exercise, such as cardiopulmonary compromise that includes hepatopulmonary syndrome and portopulmonary hypertension, and even pleural effusion (hepatic hydrothorax) in advanced stages of the disease. Those complications alter the normal exchange of gases and the mechanics of the air-fluid interphase, causing abnormal oxygenation (hypoxemia) and hypercapnia, as well as pulmonary restriction (secondary to poor O2 absorption). Other factors that can limit exercise in cirrhosis are peripheral edema, muscle cramps, and ascites, given that they impede the normal walking process and cause pulmonary restriction.33,34

The increase in the HVPG induced during exercise was a constant preoccupation among hepatologists, limiting its prescription, and even more, promoting a sedentary lifestyle in the population with cirrhosis. That recommendation derived from 2 studies that showed an acute increase in portal pressure when the patient exercised on a cycle ergometer. Due to that, the majority of studies are presently conducted on patients at low risk for variceal bleeding. However, current evidence from our group shows that in the long term (i.e., an effect that is not acute), exercise is actually associated with a decrease in the HVPG.7 That finding was later confirmed in a non-controlled study that showed portal pressure improvement after an exercise program in obese cirrhotic patients.8

Even though some studies have demonstrated a negative correlation between the Child-Pugh classification and exercise capacity measured by VO2peak,35 disease severity (evaluated through the Child-Pugh grade and MELD score) is not a contraindication for doing exercise in cirrhosis.36 In the first phases of the disease (i.e., Child-Pugh A), exercise tolerance, measured by VO2peak, is relatively conserved, compared with the final disease stages. Therefore, exercise is not contraindicated based merely on disease severity scores, albeit the focus must be prudent at advanced disease stages and different modifications must be made to the exercise program before assigning the patient to the intervention. That is something that must be considered by the physician in charge of patients with cirrhosis so that immobility is not perpetuated, followed by the consequent decrease in physical capacity.

Dietary management of patients with cirrhosis of the liver is an important aspect in the comprehensive treatment of the disease. In fact, different studies have shown that the combination of diet and physical exercise is more beneficial than either of the 2 interventions, alone.8,41

To establish a dietary plan in the patient with cirrhosis that exercises, the energy requirement based on disease stage, comorbidities, and the level of physical exercise to be prescribed must be calculated to so that there is sufficient energy intake to counteract the catabolism.

To prescribe a successful nutritional therapy, it is essential that it fully covers the energy requirement of the patient. Said requirement can be calculated in two distinct manners. Under ideal conditions, it is obtained through methods, such as indirect calorimetry, but it is not very accessible due to its lack of availability and high cost. Therefore, different formulas and recommendations have been created to calculate basal energy expenditure (BEE). The available formulas that have been utilized in exercise interventions are shown in Table 3, along with the explanation of the populations in which they can be used.

Despite the fact that the Harris-Benedict and the rapid calculation formulas are the most widely used, the Cunningham, IOM, and Owen equations have been reported to be the most appropriate in athletes and subjects in interventions that involve physical exercise. Likewise, the Mifflin-St Jeor is the formula of choice in subjects with overweight or obesity because it favors gradual weight reduction.43,52 However, the choice of the formula for calculating the BEE of each patient depends on the criterion of the nutritionist in charge, who should consider the characteristics of each patient when making the calculation.

When the BEE is obtained from a rapid calculation formula, it is not necessary to add the stress factor due to disease or physical activity. However, if it is obtained using any other formula, the percentage of calories according to the disease stress factor is added to counteract the hypermetabolism present in up to 58% of patients, and the factor of the physical activity to be carried out must also be considered. (Table 4A and B).13,53,54

Thus, the total energy required is obtained from the BEE+the stage of hepatopathy+the level of physical activity to be indicated for the patient. Table 5

Once the total energy in kilocalories is obtained, it is distributed between carbohydrates, proteins, and fats. The specific quantity of macronutrients depends on many factors, and include the amount of physical activity performed and the presence of complications.55

To begin the distribution, the quantity of proteins per kilogram of weight is first considered, based on the nutritional status of the patient:55

• •

  No malnutrition: 1.2g/kg weight/day

• •

  Mild malnutrition: 1.3g/kg weight/day

• •

  Moderate malnutrition: 1.4g/kg weight/day

• •

  Severe malnutrition: 1.5g/kg weight/day

The percentage of carbohydrates is then determined and can be from 45 to 65% of the total calorie intake. The percentage should be based on each patient, albeit a minimum carbohydrate intake of 55% is suggested in patients that perform physical exercise. The remaining calories should be received from the intake of fats. The patient should ingest at least 1ml for every kcal indicated in the diet. It is also important for the patient to maintain adequate hydration prior to and during physical exercise.44

A distribution of at least 5 meals that includes 2 snacks should be carried out. One snack can be indicated before performing the physical exercise and the other as an evening snack. In fact, even though the eating schedule depends on each patient, an interval between meals no greater than 4h is suggested, thus preventing long periods of fasting.

Supplementation with BCAAs has been studied in the cirrhotic population and their consumption has been related to an increase in muscle mass, a decrease in episodes of hepatic encephalopathy, improved liver reserve in patients with hepatocellular carcinoma, reduced insulin resistance, and improved quality of life. Therefore, their consumption is widely supported in patients with chronic hepatopathy.56,57

In a pilot study, the effect of moderate aerobic exercise plus 10g of leucine daily was evaluated. There was improvement in functional capacity, quality of life, a significant increase in muscle mass, and no signs of complications in the group that received the intervention.38 The combined treatment of physical exercise plus supplementation with the 3 BCAAs has been evaluated in other studies and the results suggest that the combined intervention has a greater effect than treatment with supplementation or exercise alone. Improvement in anaerobic capacity and a potentially beneficial effect on glycemic control were observed. Supplementation with BCAAs has also has been related to lower incidence in the characteristic complications of the disease, but more evidence is still needed in relation to the benefits of supplementation in patients with cirrhosis.58

Another strategy that has been reported as beneficial is the implementation of an evening snack that provides 200-400kcal and is particularly rich in protein (20-40g), fiber, and complex carbohydrates, given that it has shown improvement in muscle mass and energy metabolism by covering the caloric needs during the night.59,60 In fact, when combined with BCAA supplementation, an evening snack has demonstrated important improvement in nutritional parameters, nitrogen balance, and quality of life.61

Even though there needs to be more evidence supporting the safety and efficacy of exercise under specific conditions in patients with cirrhosis and portal hypertension, currently available information supports its general use in that population. To adequately prescribe exercise, a priori knowledge of the general conditions of the patient is necessary, as well as the complications derived from cirrhosis. The goal that is expected to be reached through the exercise program should also be clear, as well as the existing limitations of the healthcare center.

The present research did not require patient informed consent because it is a literature review.

The present article did not require the authorization of ethics committees because it is a bibliographic review.

The authors declare that the present article contains no personal information that could identify the patients.

No financial support was received in relation to this article.

The authors declare that there is no conflict of interest.