By Telles-Correia, Diogo Barbosa, A; Mega, Ines; Direitinho, M; Morbey, A; Monteiro, E
Background-Psychiatric diagnoses are very common in liver transplant candidates, and such diagnoses are predictive of a poor clinical evolution and quality of life after transplantation. Also, nonadherence before the transplant is predictive of nonadherence after the transplant. Methods-We studied the psychiatric and psychosocial profiles of 85 liver transplant candidates, comprising consecutive patients attending outpatient clinics of a liver transplantation unit at a public hospital. Interviews and questionnaires were used to measure personality traits, symptoms of anxiety and depression, social support, and adherence. These patients were broken into 3 groups: patients with familial amyloid polyneuropathy (n=20), patients with alcoholic liver disease (n=33), and patients with other liver diseases (n=32).
Results-About 58% of patients had a current psychiatric diagnosis (24.8%, major depressive disorder, 22.3% generalized anxiety disorder, 8.3% adaptive disorder, 2.3% abuse of or dependence on substances other than alcohol). Current psychiatric diagnosis did not differ between patients with familial amyloid polyneuropathy and patients with alcoholic liver disease. Patients with alcoholic liver disease showed lower scores for 2 protective personality traits, social support and adherence to medication, than other patients. Patients with familial amyloid polyneuropathy showed higher scores for those traits.
Conclusions-All patients waiting for a liver transplant should undergo psychiatric and psychological assessment. Some psychological characteristics such as personality traits and social support differ between clinical groups, so it may be useful to design different approaches for each group. Patients with alcoholic liver disease may require a special approach to improve adherence to medication. (Progress in Transplantation. 2008;18:134-139)
Psychiatric disorders are common in candidates for transplantation: the prevalence of depression is 33%1-6; anxiety, 34%2-6; and personality disorders, 27%.7,8 Depression and anxiety can be associated with a poor clinical evolution and a reduction in quality of life after transplantation.2,9-11 Alcohol use can also be associated with a poor clinical evolution in some cases.12-14 Some personality traits also can be associated with a poor clinical evolution, including more frequent hospitalizations and rejection episodes and alcoholism recidivisms.7,8
Nonadherence has important implications in morbidity and mortality, reduction in quality of life, and elevation of medical costs. According to Cooper et al,15 nonadherence can be a direct cause of 21% of all transplantation failures and 26% of posttransplantation mortality.
Other authors1,16-18 report that nonadherence before transplantation is predictive of nonadherence after transplantation.
We compared psychiatric features, psychosocial characteristics, and adherence of transplantation candidates among 3 specific groups of patients: candidates with alcoholic liver disease, candidates with familial amyloid polyneuropathy (FAP), and candidates with other chronic liver diseases. FAP is an autosomal dominant, multisystemic fatal disorder characterized by a progressive peripheral and autonomic neuropathy with neural and systemic amyloid deposits. The disease is caused by a mutant gene in chromosome pair 18. The amyloid protein in type 1 familial amyloid polyneuropathy of Portuguese, Swedish, and Japanese origin is the variant of transthyretin (TTR), in which methionine is a substitute for valine at position 30 (TTR Met 30). More than 90% of this TTR Met 30 is produced by the liver and the rest by the choroid plexuses. The most consensual way to treat FAP is liver transplantation in the initial stage of the disease. Patients with FAP are almost asymptomatic when they receive a transplant, unlike other liver transplant candidates, who generally have chronic liver disease.19
Methods
Participants
We studied 85 transplant candidates on the waiting list for transplantation who were attending the weekly outpatient clinics of 2 hepatologists at Curry Cabrai Hospital’s Liver Transplantation Center in Lisbon, between March 1, 2006 and March 1, 2007. All patients agreed to participate in our study and provided informed consent. These patients were divided into 3 groups: FAP group (n = 20), an alcoholic liver disease group (n = 33), and an other liver diseases group (n = 32).
Data were collected in the transplantation center by a psychiatrist and a psychologist after medical appointments with the hepatologists.
The study protocol was approved by the institutional review committee (according to ethical guidelines of the 1975 Declaration of Helsinki).
Medical Evaluation
The diagnosis of FAP was established by a neurologist and confirmed by a hepatologist. Diagnoses of alcoholic liver disease and other liver diseases were made by a hepatologist.
Psychiatric and Psychological Evaluation
Current psychiatric diagnosis and lifetime psychiatric disorders were assessed on the basis of the classification in the Diagnostic and Statistical Manual of Mental Disorders (revised 4th edition),20 using the Mini International Neuropsychiatrie Interview,21 validated for the Portuguese population by Amorim et al.22
Personality was assessed by means of the NEO Five-Factor Inventory (NEO-FFI). The NEO-FFI is a shortened version of the NEO PI-R23 (Portuguese version by Bertoquini24), a questionnaire designed to give quick, reliable, and valid measures of the 5 domains of adult personality (openness to experience: appreciation for art, emotion, adventure, unusual ideas, imagination, and curiosity; conscientiousness: a tendency to show self-discipline, act dutifully, and aim for achievement [spontaneousness vs planned behavior]; extroversion: energy, and the tendency to seek stimulation and the company of others; agreeableness: a tendency to be compassionate and cooperative rather than suspicious and antagonistic toward others [individualism vs cooperative solutions]; and neuroticism: a tendency to easily experience unpleasant emotions such as anger, anxiety, depression, or vulnerability [emotional stability to stimuli]). The 60 items are rated on a 5-point scale from 1 (“I completely disagree”) to 5 (“I completely agree”).
Social Support Evaluation
No instruments were available to assess social support in this special population, so the first 2 items of the Psychological Assessment of Candidates for Transplantation,25 which access only social support and no psychological variables (family/social support systems stability, Family/social support systems availability), were used to evaluate the social support. This questionnaire, designed to assess social support and psychological issues in transplant candidates, was adapted to Portuguese population by Telles-Correia et al,” with the author’s permission.
Measurement of Adherence
To measure adherence, we used the Multidimensional Adherence Questionnaire (MAQ), developed and validated (reliability, construct validity, and criterion validity) by Telles-Correia et al.18 The MAQ explores 3 dimensions of adherence: adherence to medication, presence at medical appointments and treatments, and alcohol consumption. Responses are rated on a 6-point scale ranging from 1 (never) to 6 (always). Dimensions’ scores can be used independently or, if summed, correspond to the MAQ’s final score.18
Statistical Methods
Statistical analysis were carried with the SPSS 13.0 for Windows software package (SPSS, Chicago, Illinois). Descriptive data were presented as absolute frequencies, percentages, and mean values.
Mean values from continuous variables with a normal distribution were compared between 2 populations by using a Student t test for independent samples. Mean values of continuous variables without a normal distribution were compared between more than 2 populations by using a Kruskal-Wallis test. A chi^sup 2^ test was used to compare percentages of noncontinuous variables between different populations.
Results
Demographic and Medical Data
Men accounted for 69.4% of the participants, compared with 30.6% for women. We found that 50.6% of the patients were less than 50 years old (mean age, 48.5 years old); 34.3% were either single, divorced, or widowed; and 87.1% had less than a high school education (Table 1).
The patients’ medical diagnoses were FAP in 23.5% (n=20), alcoholic liver disease in 38.8% (n = 33), and other liver diseases in 37.6% (n = 32; see Figure). Other liver diseases included such diagnoses as chronic viral hepatitis, liver cancer, hemochromatosis, primary biliary cirrhosis, and familial progressive cholestasis. Some patients had more than 1 liver disease diagnosed.
Psychiatric and Psychological Characteristics
In this population, only 28.2% did not have any previous psychiatric disorder, and 17.6% had had at least an episode of major depression. General anxiety disorder was diagnosed in 3.5% of the patients and 22.3% had a history of alcohol dependence or abuse disorder, 3.5% had dependence on or abuse of other substances, and 24.7% mixed alcohol/other drugs abuse/dependence (Table 2).
Only 42.4% of the patients did not have any current psychiatric diagnosis. The current diagnosis was major depressive disorder in 24.7%, generalized anxiety disorder in 22.3%, adjustment disorder in 8.2%, and dependence on or abuse of substances other than alcohol in 2.3% (Table 2). Differences Among Groups
Demographic. We found demographic differences among clinical groups in age (FAP patients were younger than other patients, P= .001), and sex (fewer female patients in the FAP and alcoholic liver disease groups than in the other liver diseases group, P= .042; Table 3).
Psychiatric and Psychological Profile. Patients from the 3 groups differed significantly in lifetime psychiatric history: compared with the other 2 groups, fewer patients with FAP had a history of psychiatric disorders, P= .001; Table 4).
The main disorders in the psychiatric history of patients in the alcoholic liver disease group were alcohol abuse/dependence and other substance abuse/ dependence; in the FAP group, the main disorder was major depressive disorder; and in the other diseases group, the main disorders were other substance abuse/ dependence and major depressive disorder (Table 5).
Analysis of the test results and of the percentages shows that the presence of a current psychiatric diagnosis did not differ significantly among the different groups (Table 4).
We found significant differences between the groups in the personality traits “agreeableness” and “conscientiousness.” Analyzing the mean ranks obtained by Kruskal-Wallis test, it is easy to conclude that the group with lowest scores for agreeableness and conscientiousness was the alcoholic liver disease group, and the group with the highest scores for these personality traits was the FAP group (P= .031; Table 6).
Social Support. Using the Kruskal-Wallis test, we found that the group with lowest scores for social support was the alcoholic liver disease group (mean rank, 23.69) and the group with the highest scores for this factor was the FAP group (mean rank, 36.30; P= .03).
Adherence. Even though we did not find any significant differences among the 3 groups in 2 of the MAQ adherence dimensions (presence at medical appointments and abstinence from alcohol), nor in the MAQ total score, we found significant differences in adherence to medication (patients in the alcoholic liver disease group had lower scores for adherence, P= .020; Table 7).
Discussion
The prevalence of psychiatric disorders in liver transplant candidates has been reported by several authors.2,4-6
According to rates obtained by means of questionnaires or scales, between 28%5 and 64%4 of liver transplant candidates have clinically significant levels of depression. In a meta-analysis, Telles- Correia et al’ reported a mean value of 33% of liver transplant candidates to have clinically significant levels of depression. This variance might be due to the different kind of populations that were assessed in each of these studies, in terms of kind of medical disease, demographic characteristics, and psychiatric comorbility.1,6 Signs and symptoms of depression are more common in patients with alcoholic liver disease, paramyloidosis, and liver cancer.4-6
Clinical significant levels of anxiety, assessed by means of questionnaires or scales, were found in between 37%5 and 31.1%2 of liver transplant candidates, with Telles-Correia et al’ reporting a mean value of 34%.
The rates of current diagnosis or lifetime alcohol dependence/ abuse differ among authors, depending on the type of liver diseases that were assessed. Rates of alcohol use can reach almost 100% in studies of patients with alcoholic liver disease.26 In studies that include different kinds of patients, rates of alcohol use can vary between 39.5%10 and 79%.9
We were unable to find any study in which a psychiatric international classification such as DSM (Diagnostic and Statistical Manual of Mental Disorders) was used to assess current or previous psychiatric disorders in liver transplant candidates, as was done in the present study.
Nevertheless, the percentages we found for current diagnosis of major depression (24.7%) and for general anxiety disorder (22.3%) were not far from the mean value for clinical significant levels of depression and anxiety showed in the studies reviewed.
All of the patients we assessed who had a previous history of alcohol dependence/abuse had been abstinent for some time. Their abstinence explains why, even though 47.1% of patients had a psychiatric history of alcohol abuse/dependence and mixed abuse/ dependence, none of the patients had this actual current psychiatric diagnosis.
The 3 clinical groups differed somewhat with respect to lifetime history of psychiatric disorders. The main psychiatric disorders in the alcoholic liver dis ease group were alcohol dependence/abuse and other substance abuse/dependence. This association is easy to understand, because the comorbidity between alcohol use and other substance use (mainly cannabis) is very common. Among patients in the FAP group, the main lifetime psychiatric disorder was major depression, which is also easy to understand because of the high incidence of depression in patients with genetic chronic diseases such as FAP. In the other liver diseases group, the main lifetime psychiatric disorders were other substance abuse/dependence and major depression. The presence of substance abuse/dependence in this group is probably due to the fact that the group includes patients with chronic viral hepatitis (mainly intravenous drug users). Current psychiatric diagnoses did not differ significantly among the 3 groups.
Some differences were apparent in personality profiles: patients with alcoholic liver disease had lower scores for agreeableness (tendency to be compassionate and cooperative rather than suspicious), conscientiousness (self-discipline, tendency to act dutifully), social support, and adherence compared with the other groups.
We also found that patients with alcoholic liver disease had significant lower social support and adherence to medication than did patients in the other 2 groups. These findings are interesting, because results of some studies indicate that social support27,28 and personality traits28,29 are essential determinants of adherence in transplant candidates and transplant recipients. Psychiatric syndromes were equally present in all clinical groups, indicating that psychiatric and psychological evaluation must be available in all clinical groups. Nevertheless, some psychological characteristics such as personality traits and social support differed among clinical groups, which might indicate that it would be useful to design different approaches for each group. Patients with alcoholic liver disease might need an approach tailored to improve adherence do medication.
Although patients with FAP presented a favorable personality profile (higher scores for openness and conscientiousness), and had the best social support and best adherence to medication, they did not differ from the other patients with respect to psychiatric diagnosis. This finding is interesting because very little has been published about the psychiatric profile of these patients.
Many studies1,12,14 have shown some psychiatric differences between patients with alcoholic liver disease and other transplant candidates. Nevertheless, we did not find any study in which patients with FAP (a rare genetic liver disease found almost only in Portugal) were compared with other liver transplant candidates.30
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Diogo Telles-Correia, MD, A. Barbosa, MD, PhD, Ines Mega, M. Direitinho, A. Morbey, MD, E. Monteiro, MD, PhD
University of Lisbon (DTC, AB) and Curry Cabral Hospital, Lisbon, Portugal
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