Quality of life for donors after living donor liver transplantation: A review of the literature

Authors

  • Neehar D. Parikh,

    1. Northwestern University Transplant Outcomes Research Collaborative, Comprehensive Transplant Center, Northwestern University, Chicago IL
    2. Division of Gastroenterology, Department of Medicine, Northwestern Feinberg School of Medicine, Chicago IL
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  • Daniela Ladner,

    1. Northwestern University Transplant Outcomes Research Collaborative, Comprehensive Transplant Center, Northwestern University, Chicago IL
    2. Department of Medical Social Sciences, Northwestern Feinberg School of Medicine, Chicago IL
    3. Institute for Healthcare Studies, Northwestern Feinberg School of Medicine, Chicago IL
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  • Michael Abecassis,

    1. Northwestern University Transplant Outcomes Research Collaborative, Comprehensive Transplant Center, Northwestern University, Chicago IL
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  • Zeeshan Butt

    Corresponding author
    1. Northwestern University Transplant Outcomes Research Collaborative, Comprehensive Transplant Center, Northwestern University, Chicago IL
    2. Department of Medical Social Sciences, Northwestern Feinberg School of Medicine, Chicago IL
    3. Institute for Healthcare Studies, Northwestern Feinberg School of Medicine, Chicago IL
    • Northwestern University Feinberg School of Medicine, 750 North Lake Shore Drive, 10th Floor, Chicago, IL 60611
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    • Telephone: 312-503-5519; FAX: 312-503-2777


  • Neehar D. Parikh's preparation of this article was supported in part by grant 5T32DK077662-04 from the National Institute of Diabetes and Digestive and Kidney Diseases (National Institutes of Health). Zeeshan Butt's preparation of this article was supported in part by grant KL2RR0254740 from the National Center for Research Resources (National Institutes of Health).

Abstract

Living donor liver transplantation (LDLT) decreases the shortage of liver grafts for patients in need of a liver transplant, but it involves 2 patients: a recipient and a living donor. Despite the magnitude of the procedure for LDLT donors, only a few studies have investigated the effect of LDLT on the quality of life (QOL) of donors. We performed a systematic search of the MEDLINE database to identify peer-reviewed articles assessing QOL in adults after LDLT donation. Nineteen studies describing 768 unique donors met our inclusion criteria for this review. The median number of donors enrolled in each study was 30 (range = 10-143), and the median follow-up period was 10.4 months (range = 3-51.3 months). Before donation, donor QOL was significantly better than that in control adult populations across all measured QOL domains. Within the first 3 months after donation, the physical domains of QOL were significantly worse than the predonation levels, but they returned to baseline levels within 6 months for the majority of patients (80%-93%). Mental domains of QOL remained unchanged throughout the donation process. Common donor concerns after LDLT included bloating, loss of muscle tone, poor body image, and fatigue. In conclusion, according to our review of the existing literature, most LDLT donors return to their baseline QOL within 6 months. However, there is a lack of long-term data on donor QOL after LDLT, and few standardized assessments include measures of common patient concerns. Additional studies are necessary to develop a comprehensive risk profile for LDLT that includes a rigorous assessment of donor QOL. Liver Transpl 16:1352–1358, 2010. © 2010 AASLD.

Liver transplantation (LT) is the only lifesaving intervention for patients with end-stage liver disease and appropriate patients with hepatocellular carcinoma (HCC). However, there is a shortage of available grafts for LT.1 One strategy for alleviating the shortage of liver grafts is the introduction of living donor liver transplantation (LDLT), in which part of a living donor's liver, instead of an organ from a deceased donor, is transplanted into a recipient. LDLT donors are typically healthy adults who do not derive any medical benefit from the procedure for themselves. Therefore, in order to justify the exposure of LDLT donors to such an operation, it is imperative for us to have a broad and clear understanding of the potential effects of LDLT on the donors.

Although the potential mortality and morbidity of LDLT donors have been described,2–4 the effects of LDLT on the donor quality of life (QOL) have not been well characterized. Donor death is the most serious complication after LDLT (estimated mortality rate = 0.28%-1.0%); however, the exact risk cannot be precisely quantified because of the lack of a centralized database measuring donor outcomes.2, 5 Short-term postoperative complications after LDLT have been well characterized: approximately 5% of donors experience a bile leak, and 9% to 19% of patients experience morbidity related to the abdominal incision.2 The sizeable minority of patients who experience medical morbidity underlines the need for improved measurements of related parameters, such as donor well-being and QOL, which are typically more difficult to quantify.

In its broadest sense, QOL can be defined as “an overall sense of well-being, including aspects of happiness and satisfaction with life as a whole.” This definition, proposed by the Centers for Disease Control and Prevention, includes specific, measurable concepts such as mental well-being, physical functioning, and overall health status, which in turn may be influenced by multiple factors, such as occupational and marital status.6 There are a number of methods for assessing patient QOL, such as physician ratings, open-ended patient interviews, and standardized patient-reported outcome measures.

This last category of assessment tools ranges from generic QOL instruments to more disease-specific instruments. Generic QOL instruments ask questions general enough for broad applicability and can be used for individuals in good health. On the other hand, targeted measures may focus on specific symptoms (eg, pain and mood) that are common in many health conditions or on concerns and symptoms specific to a disease or its treatment. Among the generic instruments, the Short Form 36 (SF-36)7, 8 is the most widely employed, and it has been used in a number of patient populations. In contrast, disease-specific instruments, such as the Liver Disease Quality of Life survey, have been created to better characterize the QOL of a targeted patient population (eg, patients with chronic liver disease).9, 10

In order to synthesize the available data on living liver donor QOL, we performed a systematic review of the literature. Specifically, our aims were to elucidate areas of specific concern for these donors and to highlight areas of focus for future research.

Abbreviations:

A2ALL, Adult-to-Adult Living Donor Liver Transplantation Cohort Study; ACSA, Anamnestic Comparative Self-Assessment Scale; ALF, acute liver failure; HCC, hepatocellular carcinoma; LDLT, living donor liver transplantation; LT, liver transplantation; MCS, mental composite score; NA, not available; PCS, physical composite score; QOL, quality of life; SF-12, Short Form 12; SF-36, Short Form 36; WHOQOL-BREF, World Health Organization Quality of Life BREF.

MATERIALS AND METHODS

We performed a systematic search of the MEDLINE database (1969-2009) to identify articles assessing QOL in living donors after LDLT. Publications were included if they were original studies using a donor-reported QOL assessment after liver donation. To obtain the most thorough article coverage, we constructed a search with the following Medical Subject Headings terms: liver transplantation (which includes all combinations of the terms liver or hepatic and transplant or graft), living donor, and quality of life. We also included any citations with the keywords QOL, HRQL (ie, health-related quality of life), or HRQOL (ie, health-related quality of life) in combination with liver transplantation. We limited our search to those publications relevant to humans and available in English. We categorized the relevant articles by the study design (prospective or cross-sectional) and the type of instrument used to measure QOL.

On the SF-36, one of the most commonly used generic surveys, QOL is divided into physical subscales (physical functioning, role-physical, bodily pain, and general health) and mental subscales (vitality, social functioning, role-emotional, and mental health). In turn, these subscales can be combined into a physical composite score (PCS) and a mental composite score (MCS). Similarly, PCS and MCS can be derived from the shorter Short Form 12 (SF-12) QOL survey. In norm-based, general population scoring, the mean score of each composite score is 50 with a standard deviation of 10.11 For the studies using these 2 generic instruments (SF-36 and SF-12), we calculated the PCS and MCS values with established scoring criteria if these scores were not provided in the original publication.11

RESULTS

Our original search strategy identified 44 citations (Fig. 1). After we limited the articles to those in English describing adult, human donors, 27 articles remained for individual review. We further excluded review articles and articles that exclusively investigated QOL in donors before LDLT. Nineteen studies describing 768 unique donors were included in this review.

Figure 1.

Search strategy using MEDLINE/Cochrane.

Study Methodology

Thirteen of the 19 studies (68%) had a cross-sectional design, and 6 (32%) had a prospective design. Seventeen studies (90%) used a validated generic QOL instrument, whereas 2 studies (10%) used an unvalidated interview. Thirteen of the 17 studies (76%) using a validated instrument used one of the generic QOL instruments: SF-36 or SF-12 (Table 1). Furthermore, 2 studies (12%) employed the World Health Organization Quality of Life BREF (WHOQOL-BREF), and 2 other studies (12%) employed the Anamnestic Comparative Self-Assessment Scale (ACSA; Table 2).

Table 1. QOL in Living Donors: Studies Using the SF-36 or SF-12 Instrument
AuthorsYearnDesignPCS*MCS*Mean Follow-Up (Months)Control Composition
  • *

    Mean normative value = 50.0 ± 10.0.

DuBay et al.262009143Cross-sectional56.451.227Normative population
Feltrin et al.16200810Cross-sectional55.646.416.2Normative population
Erim et al.122007123Prospective56.349.93Normative population
Sevmis et al.30200746Cross-sectionalNANA12
Chan et al.13200630Prospective55.149.812
Miyagi et al.25200548Cross-sectional55.555.051.3Normative population
Humar et al.27200537Cross-sectionalNANA6
Verbesey et al.14200547Prospective61.457.412
Basaran et al.15200315Cross-sectional53.547.263Healthy adults
Karliova et al.17200222Cross-sectional52.950.7NANormative population
Kim-Schluger et al.23200230Cross-sectional53.051.79.3Normative population
Beavers et al.29200127Cross-sectionalNANA20Normative population
Trotter et al.19200124Cross-sectional52.852.713.7Normative population
Table 2. QOL in Living Donors: Studies Not Using the SF-36 or SF-12 Instrument
AuthorsYearnDesignInstrumentMean Follow-Up (Months)ControlControl Composition
Kusakabe et al.22200818Cross-sectionalInterviewNANo
Hsu et al.24200635Cross-sectionalWHOQOL-BREF12YesNormative sample
Parolin et al.18200419Cross-sectionalInterview13No
Walter et al.20200328ProspectiveWHOQOL-BREF6YesNormative population
Walter et al.21200223ProspectiveACSA6YesHealthy adults
Pascher et al.31200243ProspectiveACSA12YesHealthy adults

The median number of donors enrolled in each of the studies was 30 (range = 10-143). The prospective studies followed donors for a median of 9 months after donation (range = 3-12 months), and the cross-sectional studies assessed QOL at a median of 13.7 months (range = 6-51.3 months) after donation. Thirteen of the studies (68%) made explicit comparisons to a control group. The control comparisons used either the SF-36 general population norms or data collected concurrently from a cohort of healthy adults.

Study Findings

According to our review, donor QOL is equal to or significantly higher than that of normal adult populations before donation across all measured domains of the QOL scales.12–14 For example, in Verbesey et al.'s report,14 47 donors, as assessed by the SF-36 prior to donation, reported physical and mental functioning that was nearly half a standard deviation higher than mean normative.

Although Chan et al.13 did not make an explicit comparison with the available norms, a review of their predonation SF-36 data suggests a similar predonation pattern. Six to 12 months after LDLT donation, the majority of donors report their overall QOL to be equivalent to or better than that of a normative general population or a control population of healthy adults.14–22 A few illustrative examples suggest that in the short term, donor QOL remains reasonably intact. In a sample of 28 donors 6 months after LDLT, Walter et al.20, 21 found that although some WHOQOL-BREF domain scores had worsened in comparison with predonation values, scores on the QOL instrument were still higher than those of the general population. Similarly, support for this finding is seen in Trotter et al.'s19 cross-sectional study of 24 donors; they reported donor SF-36 scores equivalent to or better than normative data. Despite the overall stability of donor QOL after donation, not all donors fare equally well in the first year after donation. In fact, 7% to 20% of LDLT donors experience reduced QOL after donation in comparison with their predonation QOL or the QOL of a control group.18, 20, 23 The issue of long-term outcomes remains an open question, however. Future research may be informed by a closer examination of the typical trajectory and correlates of LDLT donation.

That said, the existing literature does provide a snapshot of the typical trajectory of physical and mental QOL after LDLT donation. Not surprisingly, donors experience the most impact on their physical well-being within the first 3 months of donation. Both Verbesey et al.14 and Chan et al.13 reported fewer than 50 liver donors, but their studies represent the most rigorous prospective studies assessing donor QOL in any systematic fashion in our review. Notably, they reported similar statistically and clinically significant drops in patient-reported physical function immediately after donation (Fig. 2). However, donor physical function returned to nearly normal levels by 6 months, and in Verbesey et al.'s study, donor PCS values at 12 months surpassed predonation scores (Fig. 2). According to Hsu et al.,24 the most common physical complaints of donors during the postoperative period include throbbing, itching, and numbness around the surgical site; these are followed by reduced general physical vigor, sleep disturbance, and a slowed ability to react. In contrast to perceived physical function, the psychological function of donors after donation remains stable in comparison with that of normative controls, as demonstrated by the Verbesey and Chan cohorts13, 14 (Fig. 3). By and large, scores of mental well-being measures remain equivalent to those of normative populations.23, 25

Figure 2.

PCS of donors before and 12 months after LT.

Figure 3.

MCS of donors before and 12 months after LT.

According to extant data, donors typically report decrements in physical well-being associated with the immediate postoperative period, but they tend to recover to baseline levels within a year. Mental well-being appears to remain comparable to that of normative populations over the same time period.

Although such general patterns of donor QOL are useful for generalization, not all donors will follow a similar trajectory. Unfortunately, the longitudinal studies of donor QOL have not rigorously addressed the issue of predicting poor outcome, likely because of the low statistical power for modeling these associations. However, in a recent cross-sectional report, DuBay et al.26 failed to find predictors of donor PCS scores with the SF-36 instrument.

However, with respect to mental well-being, there have been some hypothesis-generating findings. It appears that the indication for LT in the LDLT recipient correlates with donor QOL before donation. For instance, donors donating to LDLT recipients with HCC and those urgently donating to LDLT recipients with acute liver failure (ALF) have a significantly worse SF-36 MCS before donation in comparison with a normative population. Specific SF-36 MCS subscales that are significantly lower in the ALF LDLT donor group versus the nonurgent LDLT donor group are bodily pain, vitality, social functioning, and emotional well-being. Three months after transplantation, mental QOL for ALF and HCC donors is not significantly different from that of a normative population.12 According to a study of 37 donors by Humar et al.,27 in comparison with left lateral segment donation, right lobe donation does not affect donor QOL. Furthermore, in studies by Kim-Schluger et al.23 and Erim et al.,12 MCS values were significantly lower in those donors whose recipients suffered complications after undergoing LDLT, although other reports have found contradictory findings.28 Advanced donor age was significantly correlated with higher mental QOL in comparison with younger donors in 1 report. A past or present psychiatric history, a graduate degree, and concerns about the donor's own well-being before LDLT donation all negatively affected donor mental QOL scores in DuBay et al.'s large cross-sectional study.26 Furthermore, those donors who had a psychiatric diagnosis at the time of donation and excessive concerns over their own health had significantly worse QOL in comparison with population norms.

Although many articles on LDLT donor QOL have used scales that are relatively general in focus, such as SF-36, several researchers have augmented their studies with more targeted symptom scales, which have provided useful information on donor well-being. Specifically, the most prominent symptoms within 1 month of donation in Verbesey et al.'s cohort14 included bloating and loss of muscle tone. In the 6- to 12-month period after donation, the most common complaints are changes in body image, increased tiredness, and fatigue.13, 21 Across various studies, 0% to 15% of donors have experienced sexual dysfunction after donation.13, 19, 23, 29, 30 Three months after donation, approximately 33% of donors are able to work, and by 12 months, 91% of donors are able to return to full-time employment.13, 19, 29 With respect to financial burden, the mean out-of-pocket financial cost for LDLT donors has been estimated to be $3660 to $5305 (US dollars).14, 19

DISCUSSION

This comprehensive review of the literature suggests that overall, LDLT donors tolerate donation well and perceive nearly normal functioning soon after donation. Although clinical morbidity associated with LDLT donation has been studied in multicenter settings, such as the National Institutes of Health–funded Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL),30 the effect of LDLT donation on donor QOL has been assessed only in a cursory manner and exclusively at single centers. On the basis of our review of the 19 available studies with QOL data for LDLT donors, we make 4 general observations. Before donation, donors have a QOL that is equal to or better than that of comparison groups drawn from the general population. In the year after donation, physical well-being decreases immediately after donation but returns to levels comparable to those of normative samples within 1 year, whereas mental well-being appears to remain relatively stable throughout the transplantation process.13, 14 That said, although the overall mental QOL (MCS) is relatively preserved in donors throughout the predonation and postdonation periods, it is diminished in those donors who donate in urgent situations, such as ALF, and in those who donate to LDLT recipients with HCC.12 Finally, cross-sectional data suggest that donor QOL after donation is diminished if the donors have psychiatric comorbidities, if they have a higher level of education, or if they express worry about their own well-being before donation.26

Although there is an emerging picture of the QOL impact of living liver donation, the literature on the well-being of LDLT donors remains limited. Many of the reviewed studies had considerable methodological limitations. Cross-sectional studies typically compared donor QOL scores to those from the general population or from selected cohorts (eg, medical students).31 These are arguably suboptimal control groups because LDLT donors often have higher than normative QOL before donation.32 A donor with QOL scores equivalent to those of the normative population after LDLT donation may actually be experiencing a relative decline in QOL in comparison with his or her pre-LDLT levels.

This dilemma leads to a broader consideration of the best control group against which living liver donor QOL should be gauged. A variety of potential populations, such as donor acquaintances, kidney donors, blood donors, healthy adults, potential but unselected liver donors, and the donors themselves before transplantation, can be considered for such a comparison. Although each of these suggestions has associated benefits and costs, we are interested in future investigations making use of acquaintance controls. In this approach, researchers would enroll acquaintances of the donors who were identified by the donors themselves. Although this approach is resource-intensive, it has been used with success in studies of Hodgkin's disease,33–36 ovarian cancer,37 and bone marrow transplantation.38, 39 Acquaintance controls tend to be similar to the donors with respect to socioeconomic status, age, education, and race: the key difference is the living donor liver surgery itself. Furthermore, the connection to an actual donor may make controls more willing and motivated to contribute to the process by partaking in research efforts.

Sixty-eight percent of the included studies were cross-sectional, and only 32% had a prospective design. The available prospective studies followed donors for a median of only 9 months and for a maximum of 12 months. As such, there is a general paucity of knowledge concerning the predictors of QOL in donors and their longer term health status. The existing literature is also hampered by low enrollment: 11 of the 19 studies (58%) enrolled 30 donors or fewer. Six of these 11 studies found no difference between donors and controls; however, because of the low sample size, it remains unclear whether this is a statistical artifact (type II error) or a true similarity. The low number of donors also precludes any meaningful subgroup analysis, which is particularly important for those few donors who do experience reduced QOL after LDLT donation. In addition, not all donors approached for participation in the cross-sectional studies actually responded. In 5 of the studies,12, 16, 23, 26, 28 the response rates ranged from 59% to 83%. This is important because there is evidence of a decreased response rate in those donors whose recipients die. For example, Miyagi et al.25 reported a 40% response rate for donors whose recipients had died.27 For this reason, care should be taken to understand what factors differentiate responders from nonresponders with respect to postdonation QOL. A final methodological concern of the existing literature is a lack of QOL instruments available for addressing the specific concerns of donors. The generic QOL instruments that have been primarily used, such as SF-36 and SF-12, may not adequately assess aspects of QOL most relevant to LDLT donation. Studies assessing psychological outcomes in donors have reported that 4% to 26% experience some level of psychological morbidity that may not fully be captured by these generic QOL instruments.40–42 Additional work is necessary to develop assessments that query the most germane aspects of donors' sense of well-being and QOL. The development of an LDLT donor–specific instrument may improve our assessment of donor well-being and may ultimately aid in the development of predonation risk stratification. Moreover, such a tool might help to predict a priori which 7% to 20% of living liver donors will experience reduced QOL.18, 20, 23 Although the initial picture is promising, there is clearly important work to be done to improve our understanding of the QOL impact of LDLT.

Along these lines, A2ALL (funded by the National Institutes of Health)30 has outlined the assessment of QOL as one of its primary objectives. Data from this multicenter, prospective cohort of donors have the potential to elucidate long-term QOL after LDLT donation.19, 43 Although A2ALL presents an important opportunity for better understanding of long-term LDLT outcomes, there are many centers worldwide that perform LDLT but have not reported data on donor QOL. In some cases, the centers may not routinely measure QOL, or if they do, they may be reluctant to publicize suboptimal outcomes. As with other outcome studies, it is important to consider the potential for publication bias. It should also be appreciated that there may be international differences in such outcomes due to differences in donor selection, health care delivery, and societal norms.

Potential donor issues to be considered in the future include body image and the impact of the abdominal incision, the financial burden, sexual dysfunction, the donor-recipient relationship, and the issue of coercion in urgent LDLT. In their qualitative study of donors, Papachristou et al.44 suggested multiple additional foci, such as preoperative emotional coping, donor autonomy, preparation for and anticipation of the postoperative course, and the impact of postoperative complications on the donor's life. Adequately powered, multicenter, long-term studies are necessary to better evaluate these and other QOL issues in donors. Furthermore, sensitive living donor–specific QOL instruments must be developed for the accurate assessment of donor QOL. The informed assessment of QOL holds the promise for more comprehensive informed consent for potential donors and for focused interventions that can improve QOL in donors after donation.

QOL and a general sense of well-being are important outcomes after any medical intervention, but they are even more important for LDLT donors because of the altruistic premise of the procedure. Providing donors with adequate risk information before LDLT donation and using evidenced-based methods to ensure the highest possible post-LDLT QOL should be prioritized when medical and surgical advances in LDLT are being developed.

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