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- PATIENTS AND METHODS
The aims of this study were to investigate the long-term effects of living donor liver transplantation (LDLT) on the health-related quality of life (HRQOL) of donors with the Short Form 36 health survey and to determine the risk factors for poor outcomes. Between June 1990 and June 2004, LDLT was performed 1000 times at Kyoto University Hospital. In July 2005, 997 of the 1000 donors were contacted by mail so that data on their HRQOL could be collected. In all, 578 donors responded (ie, there was a 58.0% response rate). The norm-based HRQOL scores for donors were better than the scores for Japanese norms across all time periods. All scores were similar for left lobe donors (n = 367) and right lobe donors (n = 211). For all donors, a multivariate logistic regression analysis revealed that age, the number of months until recovery to the preoperative health status, hospital visits due to donation-related symptoms, rest from work related to donation in the past month, and the existence of 2 or more comorbidities were significantly associated with decreased HRQOL scores. Postoperative complications and recipient mortality were not predictors of poor HRQOL. In conclusion, HRQOL was better for both right lobe donors and left lobe donors versus the Japanese norm population in the long term (mean postdonation period = 6.8 years). However, the prolongation of symptoms or sequelae related to donation lowered mental health or social functioning. The emergence of comorbidities after donation also significantly affected HRQOL in the long term. Careful follow-up and sustained counseling are required for donors with risk factors for lower HRQOL. Liver Transpl 18:1343–1352, 2012. © 2012 AASLD.
See Editorial on Page 1272
Living donor liver transplantation (LDLT) has been accepted worldwide as an alternative method for alleviating the shortage of donor organs from deceased donors. In Japan especially, LDLT has been the main treatment for end-stage liver disease, with more than 5700 LDLT procedures performed by the end of 2008.1 However, the procedure is associated with risks to the donors. The issues of postoperative morbidity and mortality for LDLT donors have been well characterized.2, 3
For healthy living donors, no medical benefit is derived from LDLT; the potential endpoint of donation is primarily psychological.4 Therefore, the transplant community has recognized the importance of understanding donor quality of life (QOL) after LDLT.5-17 According to prospective, longitudinal studies, donors typically experience decrements in physical well-being in the immediate postoperative period, but they tend to recover to baseline levels within a year. Their mental well-being appears to remain comparable to that of normative populations during the same time period.8, 9, 14 However, not all donors will follow such a general QOL pattern. Some reports have indicated that there are possible factors leading to poor donor outcomes, including the graft type (left or right lobe), donor age, urgency of the recipient's indication for transplantation, postoperative donor complications, and posttransplant recipient morbidity and mortality.16-18
At Kyoto University, the LDLT program was started for pediatric patients in 1990. With excellent graft and patient survival and proven donor safety, the application of LDLT was expanded from pediatric patients to adults. After the introduction of right lobe grafts for adult recipients in 1998,19 the number of LDLT cases increased and reached a cumulative total of more than 1000 by 2004.20 Recently, we investigated surgery-related complications in 1262 living liver donors and found that the incidence of major complications (Clavien classification grade III or greater) was 2.6% for left lobe donors and 17.0% for right lobe donors.3 At our institution (one of the high-volume transplant centers in Asia), we are aware of the need and responsibility to report the long-term QOL of donors.
In order to develop effective guidelines for donor selection and enhance postdonation follow-up and care, it is essential to identify the risk factors for poor donor QOL and to provide donor candidates with information about potential postdonation QOL difficulties as documented by rigorous studies. Unfortunately, previous studies have not successfully addressed predictors of poor outcomes, probably because of the small sample sizes and the low statistical power. Therefore, the issue of long-term outcomes remains an open question.18 The aims of this study were to investigate the long-term effects of LDLT on donor QOL with the Short Form 36 (SF-36) health survey and to determine the risk factors for poor outcomes in a large cohort.
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- PATIENTS AND METHODS
At the beginning of the LDLT series at our institution, most cases were pediatric recipients who received left lateral segments or left lobe grafts donated by young parents. After the number of adult recipients increased, the proportion of right lobe donors increased, and donors with a diversity of relationships were selected (eg, parents, children, siblings, and spouses). In this cross-sectional study, there were 578 responders to the questionnaire and 419 nonresponders. The response rate (58.0%) seemed to be comparable to the response rates (62.5%-92%) of 7 previous studies.5-7, 13, 15-17 Although answers to the questionnaire were obtained from donors with a variety of characteristics and different postdonation times, particular care should be taken with respect to factors that might differentiate responders from nonresponders.12, 18 The percentage of females and the donor ages at the time of the questionnaire and at the time of donation were significantly higher for the responders (Table 1). The donor-recipient relationships and the severity of postoperative complications differed slightly but significantly between the 2 groups. In addition, recipient mortality was significantly higher for the nonresponders versus the responders in this study. It has already been reported by some authors15, 16 that response rates are lower among donors whose recipients have died. Although the reasons for not responding were not completely clear, it is possible that the responders were not representative of all donors. This point is one of the limitations of the present study. Nevertheless, 112 donors whose recipients died still responded to the survey.
In the present study, the donors' HRQOL scores were stratified by the year of donation and compared to those of Japanese norm populations (Fig. 1). As a result, the donor HRQOL was better than the norm HRQOL (scores > 50) across all time periods: PCS was significantly higher, and MCS and RCS were equivalent to or slightly higher than the norm values, regardless of the postdonation time. These findings are consistent with previous studies5-7, 9 and suggest that, on the whole, donation for LDLT did not negatively affect the HRQOL of these donors. On the other hand, it should be noted that LDLT donors often have higher QOL scores than normative populations even before donation.8, 9 Because this was a cross-sectional study of a single time point, changes in QOL before and after the donor operation could not be evaluated in this study. However, it was implied that in most cases, this better QOL had persisted for years, and the long-term outcomes of donors (ie, >5-10 years after donation) were comparable to the outcomes of donors shortly after donation.
Although many previous studies have focused on right lobe donors,5-12 1 US study15 and 2 Japanese studies14, 16 compared QOL in RG donors and LG donors (including left lateral segment donors). These studies found no significant differences in HRQOL scores between RG donors and LG donors despite the longer incision and larger resected liver mass in right lobe donation. In the present study, the perioperative course (including the postoperative hospital stay, postoperative complications, and rehospitalization) was significantly worse for RG donors versus LG donors (Table 2). We had hypothesized that these medical conditions would more adversely affect the physical and mental well-being of RG donors and that it would become evident in studies with larger sample sizes. In addition, as shown in Table 2, the majority of the LG donors were young parents donating for their children. It was supposed that preoperative motivations and emotional coping for donation were probably different for donors with other types of relationships with their recipients, and this led to particular effects on postdonation QOL. Interestingly, however, there were no differences in the recovery time or the current PCS, MCS, and RCS values between the RG donors and LG donors (Table 2). Furthermore, it was also clarified that the donor-recipient relationship (parental or not parental) did not affect any of the HRQOL scores (Table 3).
Because there were some donors whose QOL scores were lower than those of normal populations, we investigated the risk factors or predictors of poor outcomes from several angles (Table 3). Some studies have demonstrated that donors whose recipients had major complications scored significantly lower on the MH scale than donors with recipients without major complications.6, 12 However, other studies13, 14 have reported contradictory findings. The present study did not find recipient mortality to be a risk factor for lower QOL scores. As for donor complications, Erim et al.17 indicated that donors with severe complications demonstrated a negative correlation with physical and psychiatric QOL. However, in the present study, as in some previous studies,13, 14 the occurrence and severity of postoperative complications as recorded in our database were unrelated to long-term QOL. On the other hand, donors who reported repeated outpatient clinic visits or a current need for rest from work due to ongoing symptoms or prolonged medical complications potentially related to donation showed lower RCS or MCS scores. These results implied that if donors were distressed by the sequelae of their complications for a long time, their postdonation QOL (especially mental or social QOL) significantly deteriorated. This is an important message and not an unanticipated finding that was captured through the present long-term follow-up study.
Another significant risk factor for reduced QOL was the occurrence of comorbidities that emerged after donation. It is likely that the incidence of these diseases (eg, hypertension, diabetes mellitus, and metabolic syndrome) increases as donors grow older. This is an important concern for potential donors who express concern for their own well-being because they are anxious about whether the donation procedure might increase their risk of contracting these diseases. Indeed, in this study, donors with multiple comorbidities showed significantly lower QOL scores than donors without comorbidities. However, the incidences of comorbidities were similar for the donors and the general population, and the QOL scores of the donors with comorbidities were better than the QOL scores of the general population with comorbidities. On the basis of these results, we can provide donor candidates with helpful information about the long-term effects of donation on their own health conditions. In Japan a few years ago, the highly publicized and sensationalized morbidity of living liver donors negatively affected LDLT. We hope that this study will alleviate the problem by showing positive results. At the same time, this report suggests that we need to improve the donor follow-up and care system to establish LDLT as an effective and acceptable treatment modality.
Because the safety of the donor operation and the rapid postoperative recovery of the donors are of utmost importance, from the beginning of our LDLT program, we have made it a rule to check the postoperative conditions of donors at least 3, 6, and 12 months after the operation, even in the absence of any complications. However, the present study suggests that some donors have lowered QOL for longer periods because of prolonged symptoms or psychological distress related to the donation. To improve the QOL of such donors, postdonation follow-up and care should be continued for years. In particular, it is plausible that some donors have prolonged psychological distress but are reluctant to reveal their anxiety and depression. We may need to make an effort to identify such donors and recommend them for psychiatric counseling. It is also important for transplant team doctors and coordinators to be concerned about donor comorbidities emerging after donation and, if it is necessary, to help donors to receive appropriate therapy. Furthermore, incentives to donors such as financial insurance coverage, health benefits, and absence-from-work benefits should be considered, although this is a difficult issue from a practical point of view.
In conclusion, the present study is the largest single-center report to date on the HRQOL of living liver donors (n = 578). Although this study has some limitations (as mentioned previously) and its results should be carefully evaluated, we have demonstrated that HRQOL is better for both right lobe donors and left lobe donors than the Japanese norm population in the long term (mean postdonation period = 6.8 years). The existence of surgery-related complications itself did not reduce HRQOL; rather, it was the prolongation of symptoms or sequelae related to donation that lowered mental health or social functioning. The emergence of comorbidities after donation also significantly affected HRQOL in the long term. Careful follow-up and ongoing supportive counseling are required for donors with such risk factors for lower HRQOL.