Sleep Quality and Related Factors Among Liver Transplant Recipients in Korea: A Cross-Sectional Study

ABSTRACT Background Poor sleep quality is common after liver transplantation, which lowers health-related quality of life. However, the detection and management of sleeping difficulties in liver transplant recipients have been limited. Purpose This study was designed to assess sleep quality in liver transplant recipients in Korea and associated factors, including symptom experience, depression, and family support, using the theory of unpleasant symptoms as a theoretical framework. Methods This cross-sectional study of 149 liver transplant recipients in a Korean tertiary hospital was conducted in 2019. Data were obtained using several structured self-report questionnaires, including the Pittsburgh Sleep Quality Index, Modified Transplant Symptom Occurrence and Symptom Distress Scale, Center for Epidemiologic Studies Depression Scale-Revised, and Family Support Scale. Multiple linear regression was used to determine the factors associated with sleep quality. Results The prevalence of sleep disturbance was 55% in the sample. Low sleep quality was associated with being female and with having a higher symptom experience, higher depressive symptoms, and lower family support. In the multiple linear regression analysis, depression and symptom experience was shown to significantly affect sleep quality. Conclusions/Implications for Practice The liver transplant recipients in this study reported poor sleep quality. The factors associated with the sleep quality included depression and symptom experience. To enhance sleep quality, interventions designed to reduce depression and symptoms related to liver transplantation should be provided. The results of this study may be used to develop nursing strategies to improve sleep quality in liver transplant recipients.

sleep quality, sleeping difficulties are generally underdiagnosed and not managed effectively (Reilly-Spong et al., 2013). It has been estimated, based on the Pittsburgh Sleep Quality Index scores, that 33% (Burkhalter et al., 2017) to 71% (Mendes et al., 2014) of liver transplant recipients are affected by sleep disturbances.
After liver transplantation, recipients must take immunosuppressants for the rest of their lives to reduce the rate of rejection graft loss and improve survival. However, the use of long-term immunosuppressants causes complications such as infections, hyperglycemia, hypertension, and nephrotoxicity (Herzer et al., 2020). In addition, recipients experience subjective symptoms from immunosuppressants such as pain, itching, tremors, mood swings, fatigue, nausea, and vomiting (Gunn et al., 2021), which influence sleep quality in recipients. For example, pain was shown to triple the risk in recipients of inadequate total sleep time, as measured by objective actigraphy (Reilly-Spong et al., 2013). Furthermore, weight gain, a typical symptom experienced by immunosuppressants such as steroids, has been shown to negatively affect total sleep time, sleep efficiency, and sleep onset latency in transplant recipients (Reilly-Spong et al., 2013).
Depression, which causes persistent sadness and loss of interest, is a common psychiatric disorder arising after liver transplantation. Heo et al. (2018) reported depression as the most frequently reported psychiatric comorbidity in the post-liver-transplant period, affecting 37.5% of participants. In addition, previous studies have reported a strong relationship between depressive symptoms and sleep quality in transplant recipients (Burkhalter et al., 2017;Zhu et al., 2020). Cordoza et al. (2021) found depression to be a significant factor associated with poor sleep quality in patients with solid organ transplantation.
Social support is important for patients, and especially for those experiencing stress. Social support, including emotional, instrumental, informational, and appraisal, may be provided by a patient's family members, friends, healthcare providers, or others (Swanson et al., 2018). Among the types of social support, family support plays an important role in providing transplant recipients with emotional, physical, and financial support (Golfieri et al., 2019), helping them find solutions and recover from illness and alleviating psychological problems such as stress and depression. In addition, family support increases adherence to treatments, which has a positive effect on the rate of survival in recipients (Golfieri et al., 2019). Furthermore, family support not only provides emotional and economic support but also improves self-management efficacy in facets such as sleep (H. Kim et al., 2015;Zhang et al., 2022). Therefore, family support may help improve sleep quality in Korean liver transplant recipients.
The conceptual framework used in this study was based on the theory of unpleasant symptoms (TOUS) and was designed to provide useful information for developing effective interventions to prevent, manage, and improve unpleasant symptoms (Lenz et al., 1997). This framework includes three main components: unpleasant symptoms, the affecting factors that precede these symptoms, and performance outcomes.
The three categories of affecting factors, including physiological, psychological, and situational, affect the abovementioned unpleasant symptoms. In this study, on the basis of a review of the literature, unpleasant symptoms refer to low sleep quality, physiological factors refer to symptom experience, psychological factors refer to depression, and situational factors refer to family support.
In prior studies of factors affecting sleep quality in transplant recipients, the main influencing demographic factor identified was gender, with female liver transplant recipients experiencing longer sleep latency and greater sleep disturbances than male recipients (Bhat et al., 2015;Mendes et al., 2014). In terms of clinical variables in liver transplant recipients, body mass index has been associated with low sleep quality (Reilly-Spong et al., 2013), whereas restless leg syndrome and minimal hepatic encephalopathy have been identified as factors influencing sleep problems (Akahoshi et al., 2014). In terms of psychological factors, recipients with high levels of anxiety, stress, and depression have been shown to be affected by poorer sleep quality (Burkhalter et al., 2017;Demir & Saritas, 2022;Mendes et al., 2014). However, these prior studies have focused solely on either physiological or psychological factors, which has precluded the identification of overall factors. Few studies have investigated the relationships between physiological, psychological, and situational factors and sleep quality in liver transplant recipients. In addition, few studies have been conducted on quality of sleep in liver transplant recipients in Korea, where living donor liver transplantation has been widely performed.
Therefore, this study was developed to assess the prevalence of sleep difficulties and to identify, using the TOUS, the influence of symptom experience (physiological factors), depression (psychological factors), and family support (situational factors) on sleep quality in Korean liver transplant recipients.

Research Design
In this study, a correlational, cross-sectional design was used to evaluate the influence of symptom experience, depression, and family support on sleep quality in Korean liver transplant recipients.

Setting and Sample
One hundred forty-nine adult liver transplant recipients were recruited to participate in this study from the outpatient transplant clinic of a Korean tertiary hospital from September to November 2019. Eligibility criteria included (a) being at least 18 years old, (b) at least 1 month after liver transplantation, (c) able to read and understand the Korean language, and (d) agreeing to participate and provide informed consent. Those who required emergency treatment for serious diseases such as sepsis and active lung disease were excluded.
The sample size was calculated using G*Power 3.1.9.2 (Faul et al., 2009). For a multiple linear regression with 14 expected independent variables, a medium effect size (Cohen's f 2 = 0.15), a significance level of .05, and a power of 0.80 were established. The result of the power analysis indicated the study should be performed with at least 135 participants. Therefore, 149 participants were recruited, considering an attrition rate of 10%.

Measurement
A questionnaire covering demographic and clinical characteristics, sleep quality, symptom experience, depression, and family support was used to collect the data for this study.

Demographic and clinical characteristics
The demographic characteristic data collected from participants included age, gender, educational level, marital status, living arrangements, main caregiver, religion, employment, smoking and alcohol use, coffee intake, monthly household income, and use of medications for sleep. The clinical characteristic data collected on participants included donor type, cause of liver transplantation, years since liver transplantation, comorbidities, number of immunosuppressants taken, use of psychiatric medications, and body mass index and were obtained using electronic medical records.

Sleep quality
The 19-item Korean version of the Pittsburgh Sleep Quality Index (PSQI-K; Sohn et al., 2012) was used to assess the sleep quality of the participants during the previous month in seven components, including sleep quality, latency, disturbances, duration, habitual sleep efficiency, use of sleeping medication, and daytime dysfunction. The participants were asked to rate each component using a 4-point Likert scale, ranging from 0 to 3 points with a maximum overall score of 21 points. In line with prior research, scores greater than 5 were associated with poor sleep quality (Buysse et al., 1989). The Cronbach's α of the PSQI-K was .84 in a prior study (Sohn et al., 2012) and .77 in this study.

Symptom experience
The 59-item Modified Transplant Symptom Occurrence and Symptom Distress Scale (MTSOSD-59R; Dobbels et al., 2008) was used to assess symptom experience with regard to the side effects of immunosuppressive regimens administered during the previous month. In this scale, each item represents a symptom, which is scored in terms of both symptom occurrence and symptom distress. In this study, the total score for symptom distress was used to assess symptom experience. The items used a 5-point Likert scale, ranging from 0 (not distressing at all) to 4 (extremely distressing) for symptom experience. The total possible score, calculated as the sum of the symptom distress item responses, ranges from 0 to 236 points, with higher scores indicating greater symptom experience. In addition, the frequency of symptom distress was identified to determine the symptoms that most distressed the participants. For each MTSOSD-59R item, those participants who recorded responses of zero were identified with no symptom distress and categorized as "zeros," whereas those who recorded a score greater than zero were categorized as "nonzeros." Frequency of symptom distress was defined as the number of "nonzeros" in the sample. For example, if 79 of 149 participants gave a nonzero score for "fatigue symptoms," then 53.0% of the participants would be recorded as reporting "fatigue" as a distressing symptom. Because the items of the MTSOSD-59R were deliberately composed of various contents and not homogeneous, Cronbach's α is not a useful test of validity. The content validity for all of the 59 items was ≥ .8 (Moons et al., 2001).

Depression
The 20-item Korean version of the Center for Epidemiologic Studies Depression Scale-Revised (CESD-R; Lee et al., 2016) was used in this study to assess depression during the previous 2 weeks. Each item of the CESD-R uses a 5-point Likert scale scoring system, ranging from 0 (not at all or less than 1 day) to 4 (nearly daily for 2 weeks). The total possible scores for this scale range from 0 to 80, with higher scores indicating higher levels of depression. The Cronbach's α of the CESD-R was .98 in Lee et al. (2016) and was .91 in this study.

Family support
The 12-item Family Support Scale (O. S. Kim, 1993) was originally developed for hemodialysis patients and has been used in Korea to measure level of family support for liver transplant patients (H. Kim et al., 2015). This instrument measures family support provided to patients in the facets of informational, emotional, medication, and financial support; esteem; and social network. Each item is scored using a 5-point Likert scale that ranges from 1 (not true at all) to 5 (completely true). The total possible score, calculated by summing the individual item responses, ranges between 12 and 60 points, with higher scores indicating a higher level of family support. The Cronbach's α of the Family Support Scale was .94 in O. S. Kim (1993) and .94 in this study.

Data Collection
The researcher explained the purpose and procedure of this study to eligible participants in the outpatient transplant clinic. The data were collected using self-report questionnaires from those who volunteered to participate. The participants required an average of 30 minutes to complete the questionnaire. After the participants completed the questionnaire, the researcher checked that all items had been answered and asked the participants to fill in any missing items to reduce the amount of missing data.
During the process of assessing depression in the participants, the professor of transplant surgery, one of the researchers involved in this study, was informed that psychiatric treatment was necessary for 28 of the participants with suicidal thoughts, as indicated by their responses to the questionnaire items: "I wish I were dead" or "I have wanted to hurt myself." Sleep Quality in Liver Transplant Recipients VOL. 31, NO. 4, AUGUST 2023 Ethical Considerations This study was approved by the institutional review board (Approval No. SMC 2019-08-138-003) of the study hospital. Before data collection, the participants were informed of the purpose, risks, and benefits of research participation, and written consent was obtained. The participants were assured that participation was voluntary, that data collected in this study would not be used for any purpose outside this study, and that they could end their participation at any time. The signed consent forms and completed questionnaires were sealed and collected. The personal information of the participants was coded, and the data were managed using serial numbers to ensure anonymity and confidentiality.

Data Analysis
For the descriptive statistics, all of the data were summarized as either mean and standard deviation or frequency and percentage. For the inferential statistics, independent t test and one-way analysis of variance were performed to compare differences within characteristics, and the Scheffé's post hoc test was performed. Pearson correlation coefficient analysis was conducted to determine the correlations between sleep quality and, respectively, symptom experience, depression, and family support. Finally, multiple linear regression analysis was conducted to identify the factors affecting sleep quality. In all of the analyses, statistical significance was set at p < .05, with two tails. All data were analyzed using IBM SPSS Statistics Version 25.0 (IBM Inc., Armonk, NY, USA).

Characteristics of Participants
The demographic and clinical characteristics of the participants are shown in Table 1. One hundred forty-nine postliver-transplantation participants (105 male and 44 female) were included in the analysis. The age range of the participants was 22-76 years (M = 58.19 years, SD = 8.76 years), most had received living donor liver transplantation (81.9%), and almost half were cases in which children had donated to their parents (49.7%). The posttransplant period ranged from 1 to 231 months (M = 6.17 years, SD = 5.25 years), with 55.0% of the participants having received their liver transplantation at least 5 years before participation and 17.4% having received their liver transplantation less than 1 year before participation.

Sleep Quality of Participants
The sleep quality of the participants is presented in Table 2. PSQI-K scores ranged from 1 to 21 (M = 7.16, SD = 4.15), with 55% scoring over 5, indicating poor sleep quality. The mean time of sleep latency was 33.28 minutes (SD = 36.51), with 24.8% reporting taking more than half an hour to fall asleep at bedtime. The mean sleep duration was 6.01 hours (SD = 1.50), with 14.8% reporting fewer than 5 hours of sleep per night. Slightly more than four of 10 (43%) participants had a sleep efficacy (i.e., ratio of actual sleep time to time spent in bed) below 85%, and 12.8% reported using sleep medications at least once during the previous month. In terms of sleeping difficulties experienced at least three nights per week during the previous month, over half (55.7%) reported waking up in the middle of the night or early morning, 55.7% reported getting up to use the bathroom, 14.1% reported experiencing pain, 13.4% reported coughing or loud snoring, 6.0% reported nightmares, 4.0% reported feeling overly hot, 3.4% reported feeling overly cold, and 2.0% reported being unable to breathe comfortably. In terms of self-rated overall sleep quality, 28.2% reported their sleep quality as fairly or significantly unfavorable.

Symptom Experience, Depression, and Family Support of Participants
Under the framework of TOUS, and thus in this study, the symptom experience represents physiological factors, depression represents psychological factors, and family support represents situational factors. The degrees of symptom experience, depression, and family support are shown in Table 2. The mean score for symptom experience obtained in this study using the MTSOSD-59R was 23.86 (SD = 26.34), with individual participant scores ranging from 0 to 106. The mean score for depression obtained in this study using the CESD-R was 9.93 (SD = 12.52), with individual participant scores ranging from 0 to 46. The mean score for family support was 51.66 (SD = 9.86), with individual participant scores ranging from 22 to 60.
The results for frequency of symptom experience, obtained for each MTSOSD-59R item and scored on a scale of 1-4, are presented in Table 3. The most frequently self-reported distress symptoms experienced by the participants were fatigue (53.0%), lack of energy (44.3%), muscle weakness (38.3%), sleep difficulties (37.6%), and thinning of hair or hair loss (35.6%).

Correlation Between Sleep Quality and Related Factors
On the basis of the t test and analysis of variance results, a significant association was found between gender and sleep quality (t = −2.55, p = .013), with the mean sleep quality score for men (6.57, SD = 3.84) significantly lower than that for women (8.57, SD = 4.57), indicating that the male participants had better sleep quality than their female counterparts ( Table 1).
The correlations among sleep quality, symptom experience, depression, and family support are presented in Table 4. The results of the Pearson's correlation coefficient analysis showed positive correlations between low sleep quality and, respectively, symptom experience (r = .63, p < .001) and depression (r = .73, p < .001) and a negative correlation between low sleep quality and family support (r = −.18, p = .027).

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Factors Associated With Sleep Quality
The results of the multiple linear regression analyses conducted to identify the factors associated with sleep quality among liver transplant recipients are presented in Table 5. Gender, symptom experience, depression, and family support as well as covariates (e.g., age and years since liver transplantation) were treated as independent variables, whereas sleep quality was treated as the dependent variable. The overall model explained 53.2% of the variance in sleep quality (F = 29.01, adjusted R 2 = .53). Moreover, symptom experience (β = 0.18, p = .043) and depression (β = 0.57, p < .001) were found to be significant factors influencing low sleep quality.

Discussion
The purposes of this study were to assess the level of sleep disturbance experienced by Korean liver transplant recipients and to identify based on the TOUS the respective influences of symptom experience, depression, and family support on sleep quality. The results showed sleep quality among the participants to be poor. The factors found to be significantly associated with sleep quality included depression and symptom experience.

Sleep Quality
The mean sleep quality (PSQI-K) score of the participants was 7.16 (SD = 4.15), with 55% (PSQI-K > 5) reporting poor sleep quality. This finding echoes that of other published reports, which found Pittsburgh Sleep Quality Index scores for liver transplant recipients ranging from 7.0 to 9.68 (Akahoshi et al., 2014;Mendes et al., 2014;Reilly-Spong et al., 2013), which is similar to or higher than those reported in this study. The findings suggest that sleep disturbance is a highly prevalent symptom experienced after liver transplantation. The mean total sleep time reported by the participants was 6.01 hours (SD = 1.50), which is less than in previous studies on liver transplant recipients (6.6-7.0 hours; Bhat et al., 2015;Mendes et al., 2014;Reilly-Spong et al., 2013). According to the Organization for Economic Co-operation and Development (OECD) countries' report, the average sleep time of Koreans is 7 hours and 41 minutes, which is the lowest of all OECD countries (OECD, 2016). Koreans have relatively long working hours and short sleeping durations (Park et al., 2017). Therefore, closer attention should be given to the sleep quality of liver transplant recipients, especially in Korea.

Symptom experience and depression
In terms of the predictors of low sleep quality, the results indicate that depression is a powerful factor associated with poor sleep patterns. An association between depression and sleeping difficulties and sleep disturbance was also identified in a prior study (Fang et al., 2019). Reilly-Spong et al. (2013) found organ transplant recipients with depression to be affected by a high degree of sleep disturbance, whereas Burkhalter et al. (2017) reported that organ transplant recipients who continued to experience sleeping difficulties faced a higher risk of depression. Furthermore, in this study, those who experienced symptoms after taking immunosuppressants faced a higher risk of experiencing sleeping difficulties, which is consistent with previous reports indicating that symptoms associated with taking immunosuppressants affect sleep quality (Akahoshi et al., 2014;Reilly-Spong et al., 2013). The most frequent symptoms of distress identified in this study were fatigue (53.0%) and lack of energy (44.3%). This finding is consistent with Reilly-Spong et al., which reported fatigue as a significant predictor of poor sleep quality in liver transplant recipients. These findings indicate the importance of including depression level and symptoms such as fatigue and lack of energy in sleep quality assessments of liver transplant recipients. Healthcare professionals should pay attention to and manage the depression and symptom experiences of these recipients. In addition, there is a need to develop interventions for recipients with a high degree of depression, significant symptom experiences, and low sleep quality.

Family support
Living donor liver transplantation is preferred in Asian countries such as Korea, Japan, and India. Most of the total liver transplants in the region involve living donors because of cultural beliefs that the human body should be preserved after death and because familial structures favor family members donating organs to relatives in need (Rela & Rammohan, 2021). A Korean study that investigated the motivation of family members to donate their living liver revealed this donation behavior was determined by family affection toward the recipient and by the overall well-being of the family as a whole (Ryu et al., 2019). Although family support, the situational factor in this study, was found to correlate with sleep quality, it failed to show statistical significance in the multiple linear regression analysis. This result is inconsistent with the findings of previous studies that indicate family support affects sleep quality in transplant recipients positively (Tseng et al., 2014;Zhang et al., 2022). A possible explanation for this difference may be that all of the participants in this study had a high level of family support, with minimal variation (mean = 51.66/60, SD = 9.86). In a previous study that investigated the family support received by Korean liver transplant recipients using the same questionnaire, family   support was also found to be similarly high (mean = 55.34; H. Kim et al., 2015). Family support may improve quality of sleep in recipients by providing emotional, economic, and informational support and promoting self-care such as sleep (Tseng et al., 2014;Zhang et al., 2022). Because family support is crucial for patients to improve their sleep quality, the elements that comprise this support and their relative importance should be further investigated and clarified in future studies. There have been only a few studies on family support in the context of transplant recipients. Therefore, further qualitative studies on this issue are justified, especially in cultures where living donor liver transplant is the mainstream.

Other factors
In this study, a gender effect was identified on sleep quality, with female participants reporting lower sleep quality than their male counterparts. This is consistent with the results of previous studies. Bhat et al. (2015) reported that female liver transplant recipients had significantly longer sleep latency (time required to completely sleep) than male recipients. In addition, Xie et al. (2018) found female kidney transplant recipients experienced more daytime dysfunction and lower sleep quality than male recipients. The findings of this study suggest that further, intensive assessment of sleep quality of female liver transplant patients is required and that related nursing interventions should be developed. Neither age nor posttransplant period was identified in this study as risk factors for compromised sleep quality. These findings differ from those of previous studies that found correlations between age and quality of sleep. Bhat et al. (2015) showed that older liver transplant recipients have significantly shorter sleep durations than younger recipients. Similarly, Xie et al. (2018) found that older renal transplant patients have shorter sleep durations and lower sleep quality. Moreover, the results of this study differed from the findings of Zhu et al. (2020), who reported that patients who had received their liver transplant less than 6 months before participation had worse sleep quality than their peers who had received their liver transplant more than 6 months before participation in terms of sleep latency onset, sleep efficiency, daytime dysfunction, and use of hypnotic medications. Further studies should be performed to identify the relationships between sleep quality and, respectively, age and length of time since transplantation.

Nursing Interventions for Improving Sleep Quality
On the basis of the findings in this study, there is a need for nursing care strategies that focus on improving depression, symptoms, and sleep patterns in liver transplant recipients. In addition, assessing sleep quality should be prioritized for these recipients. Effective interventions are essential to improving sleep quality in transplant recipients. A nurse-led, hospital-based foot reflexology intervention was found to be effective in improving postoperative pain, fatigue, and sleep quality in kidney transplant recipients and to improve these recipients' sleep both immediately and at 1 week after the intervention (Samarehfekri et al., 2020). In addition, attribution training, a type of cognitive therapy (Han et al., 2020), was shown to be effective in improving sleep quality in transplant recipients during the postoperative period. Barroso et al. (2019) reported that kidney recipients who participated in aerobic exercise programs achieved better sleep quality than the sedentary group. Furthermore, a mindfulness-based stress reduction intervention (Gross et al., 2010) was found to reduce anxiety, depression, and sleep symptoms, with the effectiveness maintained for 1 year afterward. In light of these and other effective interventions, nurse-led nonpharmacological interventions should be developed for and applied with liver transplant recipients.

Limitations
This study is affected by several limitations. Because this study was conducted on liver transplant recipients at a single organ transplant center and because only 44 women participated, it is not possible to generalize the results to all liver Note. Adjusted R 2 = .53, F = 29.01, p < .001. B = unstandardized regression coefficient; β = standardized regression coefficient; SE = standard error of regression coefficient.
Sleep Quality in Liver Transplant Recipients VOL. 31, NO. 4, AUGUST 2023 transplant recipients. In addition, this was a cross-sectional study performed during a specific period. Therefore, change in sleep quality over time, especially before and after liver transplantation, cannot be determined. Finally, as sleep quality was investigated using a self-report questionnaire, the responses given by the participants may be affected by subjective bias. Therefore, large, multicenter sample studies covering extended periods should be conducted in the future using objective measurement tools such as wrist actigraphy.

Conclusions
This study showed sleep disturbances to be a common problem among liver transplant recipients in Korea. In addition, depression and symptom experience were shown to affect sleep quality. On the basis of this, nursing interventions that improve sleep quality should be developed for and provided to liver transplant recipients.