Health care outcomes can be divided into three fundamental categories: survival (how long people live), cost (how much the intervention costs), and quality of life (how well people live). While QOL is an important and established health care outcome [58
] its measurement in liver transplant recipients has not been standardized or rigorously studied. However, QOL measurement has the capacity to obtain “a full appreciation of the impact of illness and treatment” [58
] given its reliance on the patient's perspective. The premise of organ transplantation in general and liver transplantation in particular is to return people to a state of health wherein they can return to a productive, fulfilling existence. This notion is at the heart of QOL measurement.
This paper is the first to critically evaluate the existing QOL instruments that have been used in liver transplantation. We believe that a thorough appreciation of the strengths and weaknesses of existing QOL questionnaires is necessary to advance further research in this area. Of note, Tome and colleagues recently conducted a systematic review of quality of life outcomes after liver transplantation [60
]. They identified 44 longitudinal studies that used a validated QOL instrument, 19 of which used the SF-36. Using a sign test on common domains for the longitudinal studies, they concluded that there was significant post-transplant improvement in general QOL, social functioning, physical health, and psychological health. While the Tome et al review is illustrative in its summary of this literature, it also highlights the diversity of QOL instruments in current use. Importantly, the lion's share of these instruments has not been designed to assess the key symptoms and issues facing liver transplant recipients. With so many QOL instruments in use and without a clear sense of their psychometric strengths and weaknesses, it will continue to be difficult to aggregate liver transplant QOL findings in a meaningful way.
To address this need, we reviewed the wide variety of instruments that have been used to assess QOL in the liver transplant population. Generic health assessment questionnaires were most common and included the SF-36, the HADS, the BDI, the EQ-5D, and the SIP. These generic instruments have enabled researchers to make comparisons between both patients with chronic liver disease and liver transplant recipients and the general public. Initial validation studies of the generic health status instruments reported strong psychometric properties. However, these instruments were not developed specifically for liver transplant recipients, and consequently there is limited data available to assess their consistency, reliability and validity in this patient population. One notable exception is a study by Gralnek et al. demonstrating good internal consistency and construct validity of the SF-36 in a group of patients referred for transplant evaluation.
In addition, a particular advantage of the SF-36 and the EQ-5D is the ability of these instruments to obtain a utility index score. Utility measures are important for the determination of quality-adjusted life years (QALYs) used in cost-effectiveness studies. Of note, the SF-6D has been developed as a utility measure from the SF-36 [61
]. This score can be determined from individual patient responses [61
] or reported population scores on the eight domains [62
]. The EQ-5D has also been frequently used for the computation of QALYs [63
In contrast to the generic instruments, targeted instruments are used less frequently (16% of included studies). However, the targeted instruments were evaluated specifically in patients with chronic liver disease and in liver transplant recipients. As such, they include elements that focus on disease-specific items. Therefore, estimates of consistency and reliability are more accurate for the population of interest: liver transplant recipients. However, the targeted instruments developed thus far are associated with their own shortfalls. For instance, the CLDQ and LDQOL were both designed to measure symptoms specific to chronic liver disease patients, not patients undergoing liver transplantation. Although the NIDDK QOL questionnaire attempted to overcome such deficiencies by including items addressing symptoms related to corticosteroid use, immunosuppressive regimens have changed significantly over time making these questions considerably less relevant.
None of the current targeted instruments address several key aspects specific to transplant recipients including issues related to post-surgical complaints such as incisional pain, hernia formation, scarring and disfigurement. Moreover, surgical patients may experience stresses related to concerns about associated complications of general anesthesia, the procedure itself, as well as concerns about disease-transmission from the donor. Transplant recipients may also experience ongoing anxiety related to both acute and chronic graft failure. Cancer risks, opportunistic infections, other side effects of immunosuppressive agents (e.g. new onset diabetes mellitus), and the risk of recurrence of primary liver disease are other highly relevant concerns. As stated above, the NIDDK QOL questionnaire attempted to address some specific concerns by including items assessing changes in facial appearance and appetite related to chronic corticosteroid use, but these concerns have become less relevant in the current immunosuppression era as most liver transplant recipients are not maintained on high dose corticosteroids in the long term with few notable exceptions. In contrast, a more relevant concern is that of nephrotoxicity leading to chronic renal insufficiency and ultimately the need for dialysis as a result of the pervasive utilization of calcineurin inhibitors [65
Additionally, the landscape of potential complications has changed over time due to the increasing use of expanded criteria livers. For instance, livers from living donors as well as those from donation after cardiac death donors are associated with increased rates of biliary complications, which may result in significant negative effects on QOL [66
]. In a sense, liver transplantation has become a victim of its own success, resulting in higher demand in the context of a limited supply of suitable donor organs. As a consequence of this growing discrepancy, sicker recipients are receiving expanded criteria grafts defined by inferior intrinsic organ quality [69
]. Although this use of expanded criteria grafts among sicker patients may still achieve acceptable survival outcomes, many of these patients require re-transplantation or survive with chronic complications and therefore diminished QOL. In addition, risk predictors in transplant recipients including the etiology of liver disease, recipient age and associated co-morbidities have changed over the past two decades. As the field of transplantation continues to evolve, patient-reported QOL outcomes need to be responsive to the consequences of different graft types, technical and surgical factors, immunosuppressive regimens, and recipient characteristics that may impact survivorship.
In addition to patient and graft survival, metrics based on QOL measurement, capturing the more subtle short- and long-term implications of liver transplantation, will be essential for providing improved patient care and for informing improved organ allocation policies. The recent Institute of Medicine report on survivorship highlights the ongoing health care needs of patients who survive cancer [71
]. Similarly, patients who survive otherwise fatal, end-stage liver disease through organ transplantation may face issues best addressed through a chronic illness model of care. Transplant survivorship elicits a need for studies to adequately address the long-term health-related QOL needs of transplant recipients. Careful collection of QOL outcomes will provide for a more accurate assessment of both donor and recipient variables, including the use of expanded criteria grafts in specific recipient populations. Moreover, several studies have demonstrated that physicians are typically inaccurate in their estimates of patient QOL [40
]. Thus, a better understanding of the QOL implications of these complex circumstances should result in enhanced physician-patient communication, which has been shown to translate into improved treatment adherence and greater patient satisfaction [40
Some limitations of this review must be noted. Several important indices necessary to evaluate the psychometric properties of the various QOL measures are not reported in the literature. For example, there is scarce data on the responsiveness over time for many of the instruments reviewed. Additionally, reliability estimates, while available in initial validation studies in non-transplant populations, were often lacking when the scale was used for liver transplant patients. Reliability is a property of a scale in a population and should be re-estimated when used in a new population. These shortcomings are primarily a function of the current state of the transplant QOL literature. The major strength of this review is its expansive look at the most prominent instruments in use, with special consideration for their strengths and deficiencies for measuring QOL in liver transplant candidates and recipients.