Symptom, Adopting Healthy Life Style, and Quality of Life in Patients with Liver Cirrhosis: A Cross-Sectional Study


 Background: Previous studies have not considered a broad range of symptoms and the association with healthy behavior and quality of life of patients with liver cirrhosis. Objectives: The purposes of the study were to examine the association of symptom with adopting exercise and consuming fruits and vegetables, and to identify factors associated with quality of life in patients with liver cirrhosis.Methods: This cross-sectional study enrolled 91 consecutive patients with liver cirrhosis in one tertiary general hospital in South Korea between February 2016 and January 2017. Each study participant completed a self-administered questionnaire that measured symptom, stage-of-change in performing exercise and consumption of fruits and vegetables, and the Korean version of the 36-item Short-Form Health Survey. Multivariate logistic regression analysis and multiple regression models was used respectively to examine the association of each symptom with engaging in exercise and increasing consumption of fruits and vegetables and to evaluate factors affecting quality of life.Results: Experiencing nausea was associated with increased intensity of exercise but experiencing shortness of breath was associated with decreased intensity of exercise. Experiencing right upper quadrant pain was associated with increased consumption of fruits and vegetables and muscle cramps, anorexia, right upper quadrant pain and body pain, itching, ascites or edema, bruising, and change in appearance negatively affected quality of life.Conclusions: The results suggest that the types of symptoms experienced by a patient with liver cirrhosis hinder or promote the patient’s adoption of exercise and dietary behavior. Experiencing symptoms may negatively affect quality of life. Caregivers should provide supportive care to patients with liver cirrhosis, which includes assessing and managing symptoms to improve quality of life.

Research staff contacted eligible patients at the ambulatory clinic and inpatient ward to explain the details of the study personally After providing informed consent, each participant was given a packet of questionnaires in quiet and independent meeting room and lled out the self-reported questionnaire in the presence of the research staff. The questionnaires collected information on sociodemographic characteristics, symptom, stage-of-change for adopting healthy behaviors based on the transtheoretical model (TTM) [14], and QOL. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as re ected in a priori approval by the a liated Institutional Review Boards of the hospital (2015-09-020-003) and the university (2015-87).

Measures Symptom
Multidimensional symptom was measured using a self-reported scale developed in a previous study [15]. This scale assesses 18 symptoms: fatigue, muscle cramps, decrease in memory, itching, dyspepsia, anorexia, dark urine, drowsiness, dry mouth, bruising, right upper quadrant (RUQ) pain, shortness of breath (SOB) and/or dyspnea, nausea and/or vomiting, body pain, urinary di culty, tarry stools, ascites/edema, and change in appearance. The patient rated each item in frequency, intensity, and distress on a four-point Likert scale (0: never experienced to 3: extremely experienced in frequency, intensity, and distress). The symptom score was calculated by summing the scores of frequency, intensity, and distress for each symptom. Thus, the score ranged from 0 to 162, with a higher score indicating having experienced more severe symptoms. The Cronbach's alpha for the symptom scale in this study was 0.96.

Adopting Healthy Behaviors
Adopting healthy behaviors was evaluated from the stage of change of TTM. The stage-of-change assessments for engaging in exercise and consumption of F&V were adapted from previous study [16], in which the measure was developed from the TTM of behavior change [14]. These measures characterized differences in the stage-of-change of goal behaviors related to exercise and diet, from pre-adoption to adoption. The ve items of each measure characterized participants into ve stages: pre-contemplation, contemplation, preparation, action, and maintenance. Pre-contemplation describes an individual who is not engaged in a new behavior and has no intention of adopting the behavior in the near future. Contemplation indicates an individual who is not engaged in the behavior but is considering adopting the behavior in the next 6 months. Preparation describes an individual who has initiated some behavior changes, but the changes are not regular. Action describes an individual who is regularly engaged in the behavior, but only began this new behavior in the past 6 months. Maintenance indicates an individual who is regularly engaging in the behavior for more than 6 months.
Prior to questioning, exercise was de ned as: "Brisk walking, cycling, swimming, mountain climbing, or another form of exercise that makes your heart pound, or makes you break out in a sweat, and is not part of your normal job activity"; F&V servings was de ned as "One serving of vegetables is equal to 1/2 cup of cooked (or parboiled) vegetable, 1 cup raw vegetable or vegetable juice, and 2 cups leafy salad greens" and "one serving of fruits is 1 cup fruit or 1/2 cup of fruit juice (orange juice, etc.) or 1/3 cup of a fruit juice blend." Participants were then asked: "On average, do you exercise regularly at least 30 min per day, 5 days a week and do you regularly eat at least ve servings of F&V per day [17]?" If a response was "Yes", the next questions were followed: "How long have you been exercising regularly at least 30 min per day, 5 days a week and regularly eating at least 5 servings of F&V per day?" The responses were: "less than 6 months" (action stage) and "6 months or longer" (maintenance stage). If a patient replied as "No" or "I am not sure" to the initial question, they were asked the following question: "Have you initiated exercising at least 30 min per day, 5 days a week and eating at least 5 servings of F&V per day?" The responses were: "Yes" (preparation stage) and "No". If the response was "No", the patient was asked following question: "Are you earnestly considering exercising at least 30 min per day, 5 days a week and eating at least 5 servings of F&V per day within the next 6 months?" The possible responses were: "Yes" (contemplation stage), "No", and "I am not sure" (pre-contemplation stage). The pre-contemplation, contemplation, and preparation were classi ed into "not engaging in exercise or consumption of F&V", and action and maintenance were classi ed into "engaging in exercise or consumption of F&V". QOL QOL was assessed using the validated Korean version of the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) [18]. This questionnaire has 36 items in 8 subscales: physical functioning, role limitations due to physical health problems, role limitations due to emotional problems, social functioning, body pain, general health, vitality, and mental health. The present study used 19 items in the 4 subscales: physical functioning, role limitations due to physical health problems, role limitations due to emotional problems, and social functioning. The score on each subscale ranged from 0 to 100, and a higher score indicated better functioning, but a higher score on role limitation indicated greater limitation. The internal consistency for the SF-36 was good (Cronbach's alpha = 0.85). The usage of the questionnaire was approved by Optuminsight Life Sciences, Inc (Lincoln, RI, USA).

Statistical Analysis
Sociodemographic characteristics and degree of dimensional symptom were presented using descriptive statistics. First, univariate analyses, the independent-samples t-test was used to examine the associations of sociodemographic parameters with the total score of symptom, and the chi-square test was used to examine the associations of sociodemographic parameters with engaging in exercise and consumption of F&V. For the chi-square test, we categorized the stages of pre-contemplation, contemplation, and preparation into "not performing exercise or consuming F&V", and the stages of action and maintenance into "performing exercise and/or consuming F&V". Then, multiple logistic regression analysis with stepwise selection was used to examine the independent effect of each symptom on engaging in exercise or consumption of F&V, with control for age, sex, marital status, having a religion, job status, monthly income, residence area, and number of family members living together. For the logistic regression analyses, the 5 stages of change were classi ed into 2 categories: "not engaging in exercise or consumption of F&V" (pre-contemplation, contemplation, and preparation) and "engaging in exercise or consumption of F&V" (action and maintenance). The results were presented as adjusted odds ratio (aOR) with 95% con dence interval (CI). Multiple regression analysis with stepwise selection, in which the main independent variables were engaging in exercise and consumption of F&V, sociodemographic characteristics, and all subscales of symptom, was also used to identify the independent effect on QOL. These results are presented as beta coe cients and standard errors. All statistical analyses were conducted using SAS 9.4 package (SAS Institute, Cary, NC).
Role limitations due to emotional problems was positively associated with experiencing muscle cramps (β = 7.18, partial R 2 = 26%, p < .0001) and change in appearance (β = 5.25, partial R 2 = 26%, p = 0.005). The linear model with these independent variables explained 52% of total variance in role limitations resulting from emotional problems (Table 4).

Discussion
The main ndings of this study indicated that experiencing SOB was associated with a reduction in exercise; experiencing nausea and vomiting was associated with adopting exercise, and experiencing RUQ pain was associated with consuming F&V. In addition, the QOL of LC patients was negatively affected by experiencing muscle cramps, anorexia, RUQ pain and body pain, itching, ascites or edema, bruising, and change in appearance. Our results suggest that the types of symptoms experienced by a patient with LC affect the patient's adoption of exercise, dietary behavior, and QOL.
The current study indicated that experiencing SOB was associated with a decrease in exercise performance. SOB can be complicated by ascites or pleural effusion in patients with cirrhosis. Dyspnea is well-known to induce exercise intolerance and individuals with daily-life dyspnea have more limited exercise capacity [19]. SOB may have inhibited exercise in cirrhosis population because this symptom becomes worse during exercise. Patients who perceive a temporary worsening of symptoms during physical activity may be less physically active [20].
Previous studies of the relationship between dyspnea and exercise intolerance were conducted in patients with pulmonary disease and multiple sclerosis. Therefore, further study is required to determine the impact of SOB on exercise levels in LC patients.
On the other hand, we found that experiencing nausea correlated with engaging in exercise and experiencing RUQ pain correlated with greater F&V consumption. According to the Health Belief Model, patients will perform healthy behaviors if they believe there is a high risk that the symptoms and complications could adversely affect their lives, and that the performance of healthy behaviors is an effective method to these symptoms. When symptoms and complications are already present, this may prompt patients to adopt healthy behaviors. The positive association between development of nausea and performing exercise may be because exercise can induce gastrointestinal symptoms, such as nausea, heartburn, and abdominal pain [21]. This is because exercise can increase the level of catecholamine, which activates adrenergic receptors and induces nausea and vomiting [22]. In contrast, most longitudinal studies of patients with cancer have reported that those who exercise experienced signi cantly less intense nausea and greater alleviation of other symptoms [23]. The current study had a cross-sectional design, so we cannot determine whether nausea led to increased exercise or if increased exercise led to nausea.
However, it is unlikely that patients with LC would exercise so intensely as to cause gastrointestinal symptoms. Thus, we believe that the experience of gastrointestinal symptoms has been a cue that increased the performance of exercise, according to the Health Belief Model.
Further longitudinal studies are required to make a de nitive conclusion on the causal relationship between symptom and the adoption of healthy behaviors.
Our results indicated that symptoms that were more frequent, intense, and distressing, differed from the symptoms that affected QOL. In particular, patients whose symptoms were more frequent, intensive, and distressing experienced fatigue, muscle cramps, and decreased memory, respectively. The ndings are in line with those of a previous integrative review, which reported that fatigue was common among populations with chronic liver disease [24]. The general ndings from the current study, which found an association of symptoms with poor QOL in patients with LC, agree with the ndings of previous studies [25].
Experiencing muscle cramps can negatively in uence physical functioning and increase role limitations. Patients with LC frequently report painful muscle cramps [26], and typically describe them as abrupt, uncomfortable squeezing or contraction of a muscle, that last seconds to minutes. Our nding supports a previous study, which reported that although muscle cramps are not life-threatening, they are a major concern and closely associated with perception of a poor health status perception among patients with LC [27]. Another previous study also showed that muscle cramps are related with signi cantly decreased QOL in patients with LC [28]. Because muscle cramps are often intermittent and subjective, and predisposition to cramping is di cult to measure using a diagnostic tool, clinicians and researchers often overlook this symptom [28]. Although muscle cramps are easy to ignore, they can signi cantly impact the QOL of patients with LC, so professional clinical nurses should help in the assessment of this symptom.
Experiencing anorexia can negatively impact physical and social functioning and increase role limitations. The nding was consistent with previous studies, which reported that patients with LC and gastrointestinal symptoms had profound reductions in physical functioning based on the SF-36 [29], and that malnutrition due to anorexia was signi cantly associated with self-perception of lower QOL in patients with LC [30].
RUQ pain and body pain can also negatively impact physical and social functioning. Our rating of symptoms according to their frequency, intensity, and distress indicated that RUQ pain ranked eleventh and body pain ranked fourteenth among all symptoms. Although pain is not among the most serious symptoms, a small change in patients' pain experience may signi cantly impact QOL, so it is important that professional clinical nurses carefully assess each patient's individual experience of pain. This nding supports a previous study that compared age and gender-matched controls and found that patients with LC were impaired in all QOL domain scores [27].
Itching and ascites/edema had a negative impact on physical functioning. Pruritus is an extrahepatic symptom that is the greatest burden for patients with LC, and our study rated it as the fourth-most serious symptom overall. Persistent itching may lead to severe sleep loss, depression, and suicidal thoughts in patients with LC [31]. Assessment of itching severity allows objective assessment of its in uence on a patient's health and QOL, so that different therapies can be implemented. According to previous studies, ascites, serum sodium levels, and lower extremity edema were independently associated with impaired physical functioning [32] and decreased QOL in patients with LC [33].
Thus, professional clinical nurses should perform systematic assessments of patients with LC who present with itching, ascites, and edema.
Role limitations due to emotional problems were greater in those who experienced changes in appearance. We speculate that a patient with LC who has readily visible symptoms (itching, edema, and ascites) may experience greater problems with body self-image and consequently greater emotional distress. Previous clinical studies of patients with cancer reported that changes in physical appearance that resulted from disease progression or treatment produce psychological distress [34,35]. The development of changes in appearance can have a profound impact on multiple functions such as working with others [36]. The present study of patients with LC indicated that emotional problems due to a poor body self-image seemed to be associated with greater role limitations. Healthcare professionals should be aware of a patient's body self-image as a potential indicator of poor role functioning when referring a patient with LC for psychosocial care.
Being employed was positively associated with social functioning [37], and being married was negatively associated with role limitations [38]. These results are in line with the common idea that a patient who is married or in a common-law relationship has better health-related QOL. Previous studies also found that socioeconomic factors affected QOL, in those patients with HCV who were married or had a cohabitant had signi cantly better QOL than their single counterparts [39]. This is presumably because a spouse can provide social and emotional support that increases QOL.
This study indicated that symptoms had an impact QOL, yet performing exercise and consuming F&V did not. Although some studies have reported exercise-induced improvement in the metabolic pro le [40], a randomized controlled trial on home-based physical activity and diet intervention showed no improvement in QOL [41]. Thus, more evidence addressing the bene ts of exercise and diet in relation to cirrhosis is still needed, with emphasis on individuals with cardiovascular risk, musculoskeletal disorders, and complications related to cirrhosis.
Cirrhosis patients need certi ed exercise and diet professionals who can perform a detailed functional assessment and design an individualized exercise and diet regimen in order to improve their QOL [6].
The symptom scores of our patients were lower than in previous studies [15], possibly because the symptoms of patients with LC may be a wide range of symptom development in those with advanced disease, whereas patients with LC may be asymptomatic for years.
Importantly, professional clinical nurses should keep in mind that although a symptom score may be low, the symptoms may still negatively affect QOL and health-related behaviors.
Clinical nurses play pivotal roles in the systematic assessment of symptoms and the implementation of treatments in the management of patients with LC. Identi cation of symptoms that occur during the different stages of LC may inform the development of interventions that target multiple symptoms at once, thereby improving the effectiveness of symptom management. Knowledge of the impact of symptom on QOL during the different stages of LC can guide best practices for symptom assessment. Our ndings suggest that professional clinical nurses require a deep understanding of the symptoms of patients with LC.
The major limitations of this study are the use of cross-sectional design and the small sample size. However, because many previous studies of this topic also examined about 100 individuals, we believe it is reasonable to compare our results with those of previous studies. In addition, our results suggest that the adoption of healthy behaviors had no signi cant effect on QOL. Therefore, further longitudinal or experimental studies for patients with LC are required to identify the causal relationship between the adoption of healthy behaviors and QOL.
Despite these limitations, very few previous studies have identi ed the various types of symptom and QOL in patients with LC.
In conclusion, this study of patients with LC indicated that the type of symptoms experienced by a patient can lead to the adoption or rejection of healthy behaviors and that the symptom of a patient can also negatively impact QOL. Patients with LC have symptom that differ in frequency, intensity, and distress, and that have different effects on QOL. Professional clinical nurses should carefully assess patients who have symptoms of anorexia, RUQ pain and body pain, ascites/edema, and change of appearance because these can negatively impact QOL, even in patients who appear to be asymptomatic. Patients with LC require specialized support for the assessment and management of symptoms. Identi cation of the association of symptom with the intention of adopting healthy behaviors and QOL provides a basis for the development of symptom management strategies and other interventions that may improve the QOL of patients with LC.