Long-Term Quality of Life for Transplant Recipients

The goal of transplantation is not only to ensure a patient's survival but also to offer the patient the same state of health that he or she enjoyed before the disease and achieve a balance between the functional efficacy of the graft and the patient's psychological and physical integrity. This is the reason that a change has taken place in the evaluation of medical interventions in the field of organ transplantation, just as in other medical fields.1, 2 Previously used parameters, such as clinical judgment, biochemical and instrumental tests, and survival rates, have been integrated with new indicators that evaluate the relationship between the costs (both human and economic) and benefits of any intervention in terms of quality of life (QOL).3, 4 A meta-analysis based on 218 studies in 23 different countries comprising 14,750 patients showed that QOL after organ transplantation improved not only in comparison with pretransplant values but also in comparison with the QOL of patients with other chronic conditions.5 However, even though this global assessment of QOL showed a significant improvement after liver transplantation, when single domains of QOL were evaluated, controversial results were found. In particular, 86% of the studies found an improvement in the physical domain, 67.4% found an improvement in the social domain, and only 61% found an improvement in the mental domain. Moreover, a recent review of instruments used to assess QOL after liver transplantation has shown that the measurement of QOL in liver transplant recipients has not been rigorously studied and is not standardized. More than 50 different instruments are available for assessing QOL in liver transplant candidates or recipients, and among these, generic health assessment questionnaires are the most widely used.6 Several studies have assessed QOL during the first few years after liver transplantation and have shown encouraging results; however, studies of the long-term evaluation of QOL after liver transplantation are less optimistic. In a recent study,7 the authors observed a significant improvement in QOL (both mental and physical components) 1 month after transplantation; however, between the first and sixth months after transplantation, only the physical components of QOL showed significant improvement. In another study by Bona et al.,8 somatization, depression, and anxiety scores improved significantly during the first year after transplantation, but they worsened again during the long-term follow-up, especially at 1 and 2 years. Conversely, physical functioning and life satisfaction scores improved significantly during the first year after transplantation, and this improvement persisted over time. These data were further confirmed by other studies showing that improvements in the emotional domains achieved during the first 3 months after transplantation had significantly decreased at 2 years of follow-up,9 with values inferior to those assessed before transplantation when the evaluation was performed 5 years after surgery.10 Only a few studies of QOL after liver transplantation have considered patients with follow-up longer than 5 years. Among these, the study by Desai et al.11 evaluated QOL 10 and 30 years after transplantation and showed that, although the patients' perception of their QOL was generally good, a small number of older individuals reported poorer QOL. In particular, patients showed a reduction in their ability to carry out physical activity in comparison with the general population. A recipient age greater than 60 years, female sex, and posttransplant complications were the most important factors associated with decreased physical functioning. These data confirm what was previously shown by Karam et al.,12 who evaluated QOL for liver, kidney, and heart recipients with more than 10 years' posttransplant follow-up and showed reduced physical functioning in liver transplant recipients. The role of the etiology of liver disease as an influence on QOL after liver transplantation has been assessed in several studies, with special attention being focused on patients undergoing transplantation for alcohol-related and hepatitis C virus (HCV)–related cirrhosis. In a study considering patients who underwent transplantation for alcoholic liver disease, no differences in returning to society with active and productive lives were reported between alcohol-related liver transplant recipients and non–alcohol-related liver transplant recipients.13 Conversely, studies assessing QOL in HCV transplant patients showed that physical, mental, and social domains were significantly worse for patients undergoing transplantation for HCV-related cirrhosis versus control patients. Although a specific correlation between HCV recurrence after liver transplantation and a decrease in the physical domain of QOL has never been shown, patients with HCV recurrence showed significantly greater levels of depression, anxiety, phobic anxiety, and paranoid ideation in comparison with HCV-negative patients.10 A more recent study by Ruppert et al.14 found that patients who underwent transplantation for autoimmune disease had decreased QOL in the physical, social/role function, personal function, and general health perception domains. Available data on QOL after liver transplantation and recipient sex are controversial. Despite a meta-analysis that showed no difference in terms of posttransplant QOL between male and female patients,15 in a more recent study, male transplant recipients reported a higher degree of overall QOL in comparison with female recipients both before and after liver transplantation.16 The role of sex in liver transplantation remains an open issue.17 The employment rate after liver transplantation could be considered a surrogate marker of the posttransplant functional status of recipients in society. The percentage of liver transplant recipients who return to work after transplantation ranges from 26% to 57%, with rates differing with the length of the follow-up period considered.18 It has been shown that employed liver transplant recipients have a significantly better QOL than those who are unemployed.18 Moreover, early retirement is the most common cause of unemployment, and those patients have worse QOL than patients unemployed for other reasons.19 A recent study based on United Network for Organ Sharing data found a high rate of unemployment after liver transplantation, with only 24% of recipients being employed within 24 months after transplantation. The demographic variables independently associated with posttransplant employment were an age of 18 to 40 years, male sex, a college degree, Caucasian race, and pretransplant employment. Patients with alcoholic liver disease had a significantly lower rate of employment than patients with other etiologies of liver disease.20 Sexual function after transplantation has become a very important parameter for evaluating QOL in organ transplant recipients. Health issues, medications, aging, and psychological and social issues may affect posttransplant sexual health. Overall, a significant improvement of sexual function after transplantation has been shown in a meta-analysis based on 7 studies.21 When sexual activity was evaluated in female liver transplant subjects, 70% of sexually active patients reported satisfaction with their sexual health. However, 2 more recent studies22, 23 described less favorable data. In one of the studies,23 23% of men and 26% of women reported decreased libido, and 33% of men and 26% of women reported difficulty in reaching orgasm with intercourse; in the other study,22 40% of the patients who underwent liver transplantation reported a decreased frequency of sexual intercourse, and among men, partial and complete erectile dysfunction was reported by 20.6% and 34.3%, respectively. At the Multivisceral Transplant Unit of Padua University Hospital (Padua, Italy), a cross-sectional study was performed to assess the prevalence of sexual dysfunction in patients with cirrhosis (35 men and 44 women) and in liver transplant patients (44 men and 54 women). Among female patients, the prevalence of sexual dysfunction was broadly similar for patients who underwent transplantation and patients with cirrhosis (65% versus 60%, P = not significant). After transplantation, sexual dysfunction was correlated with depression (p < 0.01) and reduced QOL (P = 0.02). Among male patients, the prevalence of severe erectile dysfunction was significantly greater for patients with cirrhosis versus liver transplant patients (43% versus 22%, P = 0.04). Sexual dysfunction was correlated with old age (P = 0.03), whereas after transplantation, it was greater in patients with depression (P = 0.02).24 Adherence to a medical regimen has been defined as the extent to which a patient's behavior coincides with clinical prescriptions. In an organ transplant setting, the concept of adherence is multifaceted. It may include adherence to medical prescriptions, which mean mainly but not only immunosuppressive drugs because a multitude of other drugs are prescribed to transplant recipients to prevent or treat complications of immunosuppressive therapy and other factors that negatively influence graft and patient survival.25 Among adult liver transplant patients, the rate of nonadherence to immunosuppressive drugs ranges from 15% to 40%, whereas the rate of nonadherence to clinical appointments is in the range of 3% to 47% of cases.26-31 The broad interval depends on the different definitions of nonadherence and the variety of methods used to measure adherence in the medical literature. As a matter of fact, a physician's ability to address nonadherent behavior is often limited and poorly structured, and this is probably why action taken to improve adherence does not always have the desired effect. It is rather difficult to assess transplant patients globally to distinguish between adherent and nonadherent behavior; patient behavior can vary considerably and is not necessarily always either right or wrong. Another important issue in assessing nonadherence is the lack of objective and accurate measurement methods. Several nonadherence risk factors, such as high medication costs, psychiatric disorders, the conviction that the medication is harmful, and side effects of immunosuppressive therapy, have been described among adult liver transplant patients. At the Multivisceral Transplant Unit of Padua University Hospital, we conducted a descriptive study of nonadherent behavior in 103 adult liver transplant patients with an anonymous 15-item questionnaire.25 Forty-six percent of the patients reported nonadherent behavior related to the intake of immunosuppression, 25% reported smoking, and 19.4% reported alcohol intake. Moreover, nearly 50% of the patients were not adhering to general medical prescriptions, with 11.7% taking drugs not prescribed by the transplant physician, 3.9% not attending outpatient appointments regularly, and 2.9% not performing prescribed blood tests. A longer time from transplantation was observed for patients who were not adherent to immunosuppressive therapy and general medical prescriptions in comparison with adherent patients (P = 0.02 and P = 0.03, respectively). Moreover, the proportions of men and patients on disability pensions were significantly higher among those patients failing to adhere to lifestyle recommendations versus adherent patients (P = 0.001 and P = 0.002, respectively). A single approach to promoting adherence to general medical prescriptions has been proved to be ineffectual, so a multidisciplinary strategy based on information, education, and psychological support should be adopted to achieve significant improvements in this field, not only in the short term but also in the long term after liver transplantation.