Objectives: Patients with end-stage liver disease face various psychologic challenges. We aimed to compare levels of depression, anxiety, fatigue, sleepiness, and memory in patients before and after liver transplant.
Materials and Methods: Forty patients (24 male, 16 female) were recruited from the liver transplant clinic affiliated with Shiraz University of Medical Sciences. Patients between 18 and 60 years old with at least a 6th-grade level of education were included in the study; those with severe psychiatric problems were excluded. We performed the following assessments before and 1 month after liver transplant: Hospital Anxiety and Depression questionnaires, California Verbal Learning Test, Epworth Sleepiness Scale, and Fatigue Severity Scale. Paired-sample t tests were used. P < .05 was considered significant.
Results: Level of depression in study patients increased after transplant (7.42 vs 8.42; P = .008). We found improvements in categories of immediate memory (65.23 vs 60; P = .007), short delay free recall (10.52 vs 12.52; P < .001), short delay cued recall (11.42 vs 13.00; P = .001), long delay free recall (10.80 vs 12.50; P = .003), long delay cued recall (11.80 vs 13.25; P = .003), and recognition (14.65 vs 15.42; P = .003). Patient levels of fatigue (39.9 vs 33.2; P = .029) and sleepiness (10.8 vs 7.8; P = .004) decreased. Level of anxiety did not change significantly (12.6 vs 12.8; P = .642).
Conclusions: We observed higher levels of depression but improved fatigue, sleepiness, and memory function in patients after liver transplant. No significant change in patient level of anxiety was seen. Future direction is discussed.
Key words : Anxiety, Depression, Fatigue, Memory function, Sleepiness
Liver transplantation is the worldwide-recognized radical treatment of choice for end-stage liver disease (ESLD).1 Improvements in surgical methods and immunosuppressive therapies have resulted in higher survival rates in patients with ESLD,2 with 1-year and 5-year survival rates of 85% and 70%, respectively.3 This has led to a shift in focus in the transplant community from improving the survival rate to improving quality of life in recipients.4
Patients with ESLD have different psychologic, emotional, cognitive, physical, and social challenges before, during, and after transplant.5-10 The chronic nature of the disease itself,11 the wait and anticipation for an organ donor,12 donor shortage,13 the stressful pretransplant evaluation process,14 transplant pro-cedures, need for life modifications after transplant,5 and the strict adherence to the treatment regimen,15 as well as social isolation,14 negatively affect the patient’s quality of life.14 It is not surprising that transplant candidates show high levels of anxiety13 and depression,16 which compels addressing the psychologic needs of candidates.17,18 Sleepiness and fatigue are also common events in patients with chronic liver disease, which can reduce their daily function and their health-related quality of life.19-23 In addition, impaired neuropsychologic and cognitive functions, such as memory, have been common in liver disease patients and transplant recipients.24-28 Such deficits may lead to nonadherence to medication and its debilitating consequences, including transplant rejection, infection, and even increased mortality.26 In this study, we aimed to compare patient levels of depression, anxiety, fatigue, sleepiness, and memory before and after transplant. Our findings may provide physicians with additional information to better understand the role of these factors in improving the care of ESLD patients.29
Materials and Methods
This was a pretest and posttest comparative study. Forty transplant candidates (24 male and 16 female) with ESLD were recruited during convenience sampling at a liver transplant clinic (Namazi Hospital) in 2014. This clinic is affiliated with Shiraz University of Medical Sciences (Shiraz, Iran). To be included in the study, patients had to be between 18 and 60 years old and able to read and write (education of at least 6th grade). Patients with severe psychiatric or mental problems, as indicated in their medical chart, were excluded from participation in the study. The ethics committee of Shiraz University of Medical Sciences approved the study protocol and procedure. All participants provided written informed consent before participation.
Within 1 month before and 1 month after liver transplant, participants underwent the following assessments: the Hospital Anxiety and Depression questionnaires (HADS),30 the Fatigue Severity Scale,31 the Epworth Sleepiness Scale,32 and the California Verbal Learning Test (CVLT).33 Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 16.0, IBM Corporation, Armonk, NY, USA). Paired-sample t tests were used for statistical analyses. P < .05 was considered significant.
Hospital Anxiety and Depression questionnaire
The HADS is a self-administered, reliable instrument to detect states of anxiety and depression in both inpatient and outpatient settings.30 This 14-item questionnaire has 2 subscales: a 7-item, 4-point Likert subscale between 0 and 3 for evaluation of anxiety symptoms (anxiety subscale; HADS-A) and a 7-item, 4-point Likert subscale between 0 and 3 for depressive symptoms (depression subscale; HADS-D). The score for each subscale ranges between 0 and 21. Scores of 11 and above indicate significant levels of anxiety/depression symptoms. Patients with scores of 8 to 10 are considered borderline, and scores below 8 are labeled as “noncase.”30 For our study, we used the translated Persian version of the questionnaire. The Cronbach α for the Persian version has been reported to be 0.86 for the depression subscale and 0.78 for the anxiety subscale.34
Fatigue Severity Scale
The Fatigue Severity Scale was first developed in 1989 to measure fatigue severity.31 It is a 9-item self-administered questionnaire. Patients were asked to pick a number from 1 to 7 that best described their degree of agreement with each statement in the scale, with 1 indicating strong disagreement and 7 indicating strong agreement. With the minimum and maximum scores being 9 and 63, scores greater than 36 indicate severe fatigue and the need for further evaluation.
Epworth Sleepiness Scale
The Epworth Sleepiness Scale is a simple self-administered questionnaire to measure level of daytime sleepiness.32 It consists of 8 items and produces a score of between 0 and 24. Patients are asked to rate each item on a scale of 0 to 3, based on the likeliness of falling asleep in the 8 life situations given in each statement. Scores greater than 10 indicate that the patient should seek expert medical advice, whereas scores ranging from 0 to 9 are considered normal.
California Verbal Learning Test (Persian)
The CVLT is a widely used neuropsychologic test.33 It measures repetition learning, serial position effects, semantic organization, intrusions, and proactive interference, which are the key constructs in cognitive psychology.35 The CVLT produces a wide variety of measures, including immediate memory, short delay free recall, short delay cued recall, long delay free recall, long delay cued recall, and long delay recognition.
The CVLT-Persian36 assesses the patient’s recall ability. In our study, a medical student read a list of words (list A) to patients, and they were asked to recall as many words as possible (immediate memory). This process was repeated 4 more times. After completion of these trials, the medical student read a different list of words (list B) to the patients to distract them and asked the patients to recall as many words as they could from this list. Subsequently, patients were asked to recall as many words from list A as they could (short delay free recall). During the recall process, patients were cued to remember the groups in which the words belonged to (ie, animal, transportation, vegetable, and furniture, which tested short delay cued recall). After the completion of this phase, patients completed other sections of the study questionnaires, which took approximately 20 minutes. After this long delay, patients were asked to recall as many words as they could from list A, before (long delay free recall) and after (long delay cued recall) they were provided with the cue categories. Finally, patients were asked to which of the lists the word belonged to (A or B), which tested recognition. Patients scored 1 point for each word that they recalled in each category, with the highest score being 16 for recalling a total of 16 words.
Our study included 40 patients (24 men and 16 women). The mean age of participants was 38.65 ± 15.28 years. Table 1 shows the demographic data of the patients.
The changes in mean scores for study measure-ments are provided in Tables 2 and 3. As indicated, there were statistically significant differences in before versus after transplant measures of depression symptoms (7.42 vs 8.42; P = .008), fatigue (39.9 vs 33.2; P = .029), daytime sleepiness (10.8 vs 7.8, P = .004), immediate memory (65.23 vs 60; P = .007), short delay free recall (10.52 vs 12.52, P < .001), short delay cued recall (11.42 vs 13.00, P = .001), long delay free recall (10.80 vs 12.50, P = .003), long delay cued recall (11.80 vs 13.25, P = .003), and recognition (14.65 vs 15.42; P = .003). However, the differences between mean scores of anxiety before versus after transplant were not statistically significant (12.6 vs 12.8; P = .642).
In this study, we aimed to compare patient levels of depression, anxiety, fatigue, sleepiness, and memory before and after transplant. Our findings revealed that, although levels of depression increased significantly after transplant, changes in levels of anxiety were not statistically meaningful. In addition, we found that fatigue and sleepiness levels were significantly decreased. Moreover, we found improvements in all levels of recall after transplant.
The existing scientific studies on associations between transplantation and depression are mixed, which could be due to use of different study approaches, patient populations, and measurements. In a study by Wang and associates, the self-rated level of depression after liver transplant was higher than that of a norm group.37 In a study of children (age ranging from 0 to 18 years) after transplant, Karayurt and associates found no statistically significant differences in level of depression between the patients and their healthy counterparts.38 Another recent study investigating hopelessness, suicide ideation, and depression (using Beck Depression Inventory) in chronic kidney disease patients on hemodialysis and kidney transplant recipients found high prevalence of depressive symptoms in both groups, although no significant differences were observed between the groups.39
Our finding of higher depression scores in patients after liver transplant suggests a need for further subsample study (perhaps pediatric vs adult patients) to identify what factors are associated with more depressive symptoms after liver transplant. It has been reported that patients who receive grafts from living donors are less likely to be depressed than those who receive grafts from deceased donors.39 Identification of factors leading to posttransplant depression could help with strategizing efforts aimed at facilitating return of these patients to an active life.
Liver transplant patients commonly experience higher levels of anxiety.40 Waiting for a donor organ as the only life-saving treatment option, accepting that available donations are far less than the demand, the stressful pretransplant evaluation process, and being an uncertain or high-risk candidate12-14 are a few factors reported by patients to rationalize the presence of their pretransplant anxiety. Our finding, however, reveals that anxiety levels were the same before and after transplant. This suggests that, for liver transplant patients, anxiety remains a common denominator throughout treatment. Existing evidence suggests that the need for life-long lifestyle modifications could evoke persistent anxiety.5 Patient age, family monthly income, and mental health of close relatives have also been associated with anxiety and depression in patients after transplant.37,41 Others have suggested a positive correlation between physical and mental health-related quality of life in posttransplant patients.42
The average daytime sleepiness in our sample reduced from a score of 10.8 before transplant to 7.8 after transplant (P = .004). It has been reported that daytime sleepiness is associated with nonadherence to immunosuppressant therapies in renal transplant recipients.43 Efforts to maintain sleep habits of patients posttransplant should be integrated into the care of these patients.
We found that fatigue improved after transplant. However, in a 2-year follow-up study, fatigue remained a persistent problem for liver transplant patients.23 Different liver disease diagnoses may be associated with different levels of fatigue postoperatively. In one study, physical fatigue continued to be a problem for transplant recipients diagnosed with cirrhosis.44
Transplant recipients who acknowledge having fatigue also express lack of motivation and social interest, malaise, lethargy, and discomfort, which together affect daily function and quality of life.22,45,46 Further studies could test how integration of complementary and alternative medicines such as yoga and mindfulness practices can lead to better outcomes for these patients.
In this study, we focused on memory as a function of cognitive productivity. Of the 6 categories of immediate memory, short delay free recall, short delay cued recall, long delay free recall, long delay cued recall, and recognition, we found improve-ments in all after transplant. This finding supports the results of previous studies that showed the positive effects of liver transplant on cognitive function.47 Others have refuted this finding, reporting that cognitive impairments persisted long after liver transplant.48 These findings imply that neurocognitive impairment could be clinically hidden and underestimated,49 suggesting that regular neuropsychologic tests in liver disease patients and liver transplant recipient may benefit their disease outcome.
Our findings have several limitations. Our small sample size prevented us from performing analysis across different end-stage liver disease diagnoses, such as comparing alcoholic and nonalcoholic cirrhotic patients. In addition, the lack of randomization in sample selection prevented our finding from being generalized. However, our findings may still benefit the future care of these patients and prompt further investigations of the link between liver transplant and depression, anxiety, fatigue, sleepiness, and memory function, by using longer and more methodologically rigorous posttransplant follow-up. Health care providers of transplant patients should inform patients and their caregivers of the risk of posttransplant depression. Providers should also be cognizant of effective psychopharmacologic treat-ments, group and individual therapies, support services, and mentoring, which may benefit patients after transplant.
In conclusion, we observed higher levels of depression in patients after versus before liver transplant. There were no significant changes in levels of anxiety before and 1 month after transplant. However, fatigue and sleepiness, as well as memory function, significantly improved in patients after liver transplant. Future research should evaluate further time points and involve serial evaluations over the first year posttransplant, to allow a more overall psychologic profile of the patient.
DOI : 10.6002/ect.2017.0135
From the 1Transplant Research Center, the 2Department of Psychiatry, the
3Research Center for Psychiatry and Behavioral Sciences, and the 4Shiraz
Nephrology and Urology Research Center, School of Medicine, Shiraz University of
Medical Sciences, Shiraz, Iran; the 5Department of Psychiatry, Charles Drew
University of Medicine and Science and David Geffen School of Medicine,
University of California, Los Angeles, California USA
Acknowledgements: This study was Dr. Mohammad Baghernezhad’s graduate thesis, which was supported by grant No. 92/1/1/5668 from Shiraz University of Medical Sciences.The authors have no conflicts of interest to declare. We are grateful to Dr. Ali Akbar Asadipooya for sharing his pearls of wisdom during the course of this research, and we thank Dr. Zabihi and Dr. Ghaedsharaf for assistance with methodology and interview.
Corresponding author: Shahrzad Bazargan-Hejazi, Department of Psychiatry and Pediatrics, Charles Drew University of Medicine and Science, and Department of Psychiatry, David Geffen School of Medicine, University of California, Los Angeles, CA, USA and, Kermanshah University of Medical Sciences, Kermanshah, Iran
Phone: +323 357 3464/+323 563 4957
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Table 1. Study Sample Characteristics
Table 2. Patient Reported Depression, Anxiety, Fatigue, and Daytime Sleepiness Before and After Transplant
Table 3. Patient-Reported Memory Before and After Transplant