Study population and data collection
In this prospective observational study, we enrolled 75 liver transplantation recipient candidates aged 16 years or older (ALD-RC, n = 19; NALD-RC, n = 56) who were referred to our hospital from January 2011 to December 2019. The recipient candidates in this study were patients who met the physical criteria for liver transplantation based on the ethical guidelines of the Japan Society for Transplantation [17,18].
To conduct appropriate assessment of indications for liver transplantation, our center created a transplantation medical team in 2004. This team comprises transplant surgeons, gastroenterologists, hepatologists, psychiatrists, transplant coordinators, and psychologists. When patients are referred to our hospital, transplant surgeons, gastroenterologists, and hepatologists evaluate physical aspects such as transplantation indications, primary liver disease, blood tests, model for end-stage liver disease score, and Child–Pugh classification. In Japan, the transplantation criteria about alcohol use disorder indicates that absolute contraindication only for alcohol use disorders without 6 months of sobriety (changed to 18 months after 2014), therefore, ALD-RC are required to have followed a 6-month abstinence rule at the initial assessment. Following physical evaluation, transplant coordinators check their family situation and support system. Psychiatrists and psychologists check psychosocial characteristics, namely performance on the Visual Analogue Scale (VAS), Alcohol Use Disorders Identification Test (AUDIT), Hospital Anxiety and Depression Scale (HADS), Beck Depression Inventory (BDI), Brief Evaluation of Medication Influences and Beliefs (BEMIB), Social Support Questionnaire (SSQ; Number of Persons, NP; Satisfaction Rating, SR), Temperament and Character Inventory (TCI), Parental Bonding Instrument (PBI), and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36; Physical Component Summary, PCS; Mental Component Summary, MCS).
The team continues to hold interdisciplinary conferences every week to share patient information . After liver transplantation, all patients received ongoing support from psychiatrists and psychologists and, in cases of comorbid psychiatric disorders, received psychiatric treatment such as pharmacotherapy or psychotherapy.
In this study, we conducted the following three investigations. First, we compared psychosocial characteristics, namely scores on the VAS, AUDIT, HADS, BDI, BEMIB, SSQ (NP/SR), TCI, PBI, and SF-36 (PCS/MCS), between ALD-RC and NALD-RC before liver transplantation. Second, we evaluated psychosocial characteristics, namely scores on the VAS, AUDIT, HADS, BDI, BEMIB, SSQ (NP/SR), SF36 (PCS/MCS), at the preoperative period and at 3 and 12 months after liver transplantation for patients who received liver transplantation. Third, we compared SF-36 scores between ALD-R and published Japanese norms at 3 and 12 months after liver transplantation. Japanese norms were obtained from data reported by Fukuhara et al., “Manual of SF-36 Japanese version 1.2” [19-21].
Although we cannot rule out selection bias, we hoped to avoid this as much as possible by identifying all patients diagnosed within a specific period of time.
The VAS assesses subjective characteristics or attitudes that cannot be directly measured. Scores range from 0 to 100 points [22,23]. We measured pain in this study. The AUDIT is a measurement tool to screen patients for possible alcoholism. The AUDIT comprises a 10-item questionnaire and is a simple and useful method for early detection of harmful alcohol use . The HADS scale assesses levels of anxiety and depression. The Japanese version of the HADS questionnaire was used to assess patients’ depression severity [25,26]. Higher scores indicate more severe symptoms. The BDI is a self-rating measurement tool developed by Beck et al.; it has high diagnostic utility for depression [27,28]. The BEMIB was developed to identify non-adherence in patients with psychiatric disorders and consists of an 8-item scale. In this study, we used the Japanese version of the BEMIB . The SSQ measures social support and satisfaction with social support from the perspective of the interviewee. The SSQ consists of two subscales: the Number of Persons (NP) subscale, which reflects the sum of the perceived number of others who provide social support, and the Satisfaction Rating (SR) subscale, which reflects the sum of the individual’s degree of satisfaction with perceived social support. In this study, the six-item Japanese version of the SSQ was used [30,31]. The TCI assesses personality characteristics. According to Cloninger [32,33], personality can be divided into temperament (Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence) and character domains (Self-directedness), Cooperativeness), Self-transcendence). Participants respond to each TCI item by answering “true” or “false” and a total score for each temperament and character dimension is calculated. In this study, we used the Japanese version of the TCI . The PBI assesses perceived rearing . The PBI is a self-report questionnaire that evaluates a person’s perception of how they were raised by asking the respondent to recall their parents’ child-rearing attitudes before the age of 16 years. The PBI consists of four categories: paternal care, paternal overprotection, maternal care, and maternal overprotection, and scores are obtained for each category. In this study, we used the Japanese version of the scale . The SF-36 is a 36-item patient-reported survey of patient health. Administration of the SF-36 generates a health profile on eight domains: general health, physical function, role physical, bodily pain, vitality, social functioning, mental health, and role emotional. The SF-36 also provides two higher-order summary scores: the physical component summary (PCS) and the mental component summary (MCS). Scores for each summary range from 0 to 100. Higher scores indicate better health-related quality of life . Published Japanese norms were used as a comparison for SF-36 scores. We compared recipients’ health as measured by the SF-36 with national standards using these norms [19-21].
Statistical analyses were performed using SPSS, version 25 (IBM, Armonk, NY, USA). Continuous variables were compared by t test and Mann-Whitney U test.
Homogeneity of variance was evaluated using Levene’s test. For between-group comparisons, Student’s t-test was used if the data showed homogeneity of variance. In the absence of homogeneity of variance, Welch’s method was used. The chi-square test was used to examine differences between categorical variables. A P-value of <0.05 was regarded as statistically significant. We did not determine an a priori sample size; owing to the small pool of study subjects, we conducted the analysis using the maximum sample size available. We compensated by checking the effect size after the analysis. Because of the exploratory nature of this study, we did not adjust for multiple comparison issues. A statistical review of the study was performed by a biomedical statistician.
The study protocol was performed in accordance with the Declaration of Helsinki and was approved by the ethics review committee of Nagoya University Graduate School of Medicine (Approval No. 2012-0339) and all participants provided written informed consent to take part in the study. This study was fully supported by a Grant-in-Aid for Scientific Research (C, No. 24591875) from the Japanese Ministry of Education, Culture, Sports, Science and Technology and by a grant from the Japanese Society for the Promotion of Science.