Although a number of instruments are used to measure HRQOL in liver transplant recipients, none clear standard exists [7]. There has been an attempt at developing a more specific post-liver transplant-specific questionnaire, but this has not yet been validated [3].

One of the commonly used instrument in liver disease is the short-form 36 (SF-36) , a generic and validated survey commonly. In a systematic review of long-term HRQOL outcomes, the authors identified 8 of the 23 studies which utilized the SF-36 HRQOL survey [7]. The SF-36 is a self-rated survey that is used to compare health status across diverse populations, including different disease processes, and measures 36 items [8, 9]. These items are further divided into eight subscales including general health, physical function, bodily pain, mental health, and four others. A score is then generated for each subscale that can be compared between different populations.

There are a number of limitations understanding HRQOL in liver transplant recipients. For instance, unlike studies assessing HRQOL in patients who undergo primary transplantation, there are few studies measuring HRQOL in patients following liver retransplantation [7]. There is also a paucity of data of HRQOL according to indication for liver transplantation. Most studies on HRQOL provide an overall measure rather than stratification by underlying cause of liver disease [7, 10]. Although it is likely that the etiology of liver disease would have a unique effect on HRQOL, evidence of this effect has so far been less clear [10].

There is strong and convincing evidence of a sustained benefit to HRQOL for post-transplant patients compared to the same patients in the pre-transplant period or an equivalent waiting list group of patients with chronic liver disease [7, 10]. This benefit is found regardless of the whether the instrument used to measure HRQOL and was seen in all categories measured including general health, social interactions [4], emotional, physical well-being, and psychosocial function [11–16]. The sustained benefits in HRQOL ranged anywhere from 3 to 8 years before a significant decrease occurred [14, 17, 18]. Patients that have survived over 10 years post-transplant show a decrease in most HRQOL domains over time, though the rate at which this occurred and after how many years continued to be variable [4, 13, 19–21]. Although there was a decrease in QOL, the HRQOL scores were still consistently higher among post-transplant patients when compared to pre-transplant patients with chronic liver disease [4, 13, 16, 22].

Although post-transplant recipients have much better HRQOL scores as compared to the waiting list population, the comparison of post-transplant patients to a healthy comparison group has conflicting data with regard to HRQOL scores [7, 10]. Several studies have shown that the HRQOL of patients post-transplant can be similar to the general population [4, 15, 17, 18, 23–25]. The magnitude of improvement of scores among the different domains that comprise HRQOL such as general health, mental health, physical role functioning, emotional role functioning, and other domains in transplant recipients can vary according to HRQOL instrument used [7, 10]. However, the domains of general health and mental health were on average found to be similar between the general population and post-transplant patients [4, 15, 17, 18, 23–25]. Increased physical activity may be a good predictor of sustained QOL benefits post-transplant, though this needs further validation [4, 22, 25].

Other studies have shown that the post-transplant population has significant impairment in almost all domains when compared to the general populace [10]. Interestingly, the majority of studies that show poorer QOL for the post-transplant group ranged from 6 months to 10 years with most studies having follow-up times before the 5-year post-transplant mark [10]. Whereas the studies that showed some similarities in certain domains had follow-ups that were usually greater than 5 years [7], one domain that all studies concur on is a poorer performance in physical function, which had consistently lower scores in the post-transplant group when compared to the general population [7].

Functional status has been defined as “…an individual’s ability to perform daily activities required to meet basic needs…maintain health and well-being” [26]. The functional status is a valuable predictor of HRQOL; better functional status correlates with increased HRQOL. Employment status and amount of physical activity are commonly used as surrogates when assessing the functional status of post-transplant patients [7, 10].

There are a number of l imitations when assessing employment status and physical activity status in liver transplant recipients. For example, while the majority of post-transplant patients are of working age (28–59 years), the number of patients who were working prior to transplantation is highly variable [7]. Up to half of patients undergoing liver transplant were employed prior to transplant in studies that measured this [27, 28], and 67 % of patients were unemployed or retired by the 8th-year post-transplant [27, 28]. Important factors that can explain the lower rate of employment can be related to pre-transplant factors such as lack of disability prior to transplantation and number of hours worked [29]. Post-transplant factors include the transition into retirement and the disability status that liver transplantation offers after transplantation [10]. Those patients that do stay employed after transplantation have higher HRQOL scores [28, 30, 31].

Encouraging patients to regularly engage in regular cardiovascular exercise (i.e., three times weekly ≥30 min per session) has been shown to improve scores in multiple HRQOL domains including physical symptoms, fatigue, social functioning, and general health [14, 25]. Increased physical activity is also associated with decreased surgical complications after transplant [23, 25]. Although encouraging patients to regularly engage in physical activity is beneficial, this may not be possible among all patients. Many patients have multiple comorbid conditions and may not be able to achieve the high level of physical activity that are usually studied [25]. Further study into whether lower levels of activity still offer the same benefit that regular physical activity confers in the future will be useful in this regard.

Sexual function is another measured domain of functional status that did not significantly improve after liver transplantation [7, 10]. There may even be deterioration in sexual function following transplantation [32]. Again this data should be carefully interpreted as there can be multiple confounding factors [10]. Self-assessment questionnaires on sexual health are known to be difficult to interpret, and the presence of encephalopathy prior to transplantation can skew measurement of this domain [10]. In apparent contradiction, one long-term study demonstrated an improvement in sexual function following transplantation, indicating the need for further study [4].

The number of patients that need lifesaving liver transplantation is much greater than the number of grafts available. This has led to the development of the technique of living donor liver transplantation (LDLT) in which healthy individuals donate a portion of their liver. An estimated 12,000 LDLTs have been performed worldwide [33]. The majority of donors following donation have minimal complications upon follow-up [34, 35]. The most common short-term complications include bile leaks and other biliary complications, occurring at rates of about 5 %, and abdominal incision-related issues such as pain or incisional hernia, occurring between 9 and 19 % [35]. Other characterized complications include bleeding, ileus, or infections [36]. Due to the short-term complication, there is a transient decrease in HRQOL scores seen that generally lasts for about 3 months [35]. After approximately 6 months, most donors return to a HRQOL similar to the pre-donation period or a healthy comparison group [34, 35]. Of note, anywhere from 7 to 20 % of donors experience a sustained reduction in HRQOL following liver transplantation due to long-term complications of donation such as chronic pain and bile strictures [34]. Other studies have shown a median morbidity rate of 16.4 % following donation [35]. Thankfully, the mortality of donation is low, ranging from 0.28 to 1 % of all donations [35]. Nevertheless, this data indicates that close follow-up is essential to effectively prevent poor outcomes for post-donation patients.

Instruments for assessing HRQOL for donors have not been standardized [35]. The use of the SF-36 form is once again prevalent but still multiple different HRQOL are used [37–42]. The results of most of the studies demonstrate that across all domains, donors have a significant transient decrease in HRQOL followed by a recovery to their baseline HRQOL prior to transplantation [34, 35]. Physical health was an area that showed decline in the immediate post-op period but improved back to a normal level among the majority of patients [34, 35]. Some patients do experience complications related to surgery or have long-term discomfort but overall remain in good physical condition [35]. Mental health did not decline among most post-op studies and remained at preoperative levels, though one study did show a statistically significant lower mental health score but this was still above the norm [35, 43]. Psychosocial function is more complex than previously thought and encompasses multiple domains such as interpersonal, work-related, and financial impact [35]. Work-related impact is generally minimal as the majority of patients return to work [34, 35]. Most studies show a return to work rate of over 90 % within 12 months [35]. Interpersonal and financial impacts are areas that are evolving; financial impact includes immediate post-op follow-up that is generally covered by insurance and long-term postoperative care that is usually an out-of-pocket expense [34]. The mean out-of-pocket expense for patients is estimated around $3660 and $5305 USD [44, 45].

Interperson al impact is more difficult to assess, but the underlying theme is that patients who freely volunteer to donate instead of feeling coerced into donating have better interpersonal functioning [35]. To address coercion, a five-stage decision-making model has been established to guide patients and professionals through the process although this has not been standardized [46]. There has been no documented detriment or benefit to donating the right or left lobe of the liver, and HRQOL is essentially the same for patients who donate either lobe [35, 43]. Important caveats are that most of the data follow-up are not long term [34, 35]. Studies with longer follow-up times include a 2-year prospective study that corroborates the data from the older studies [47]. Another long-term study with a mean follow-up time of 6.8 years post-donation shows that the HRQOL scores generally hold either at or above the general population for most domains [43]. One domain that showed a poorer than average score was the role/social composite score (RCS) [43]. This is in line with the complexity that psychosocial function has been discovered to have [34].

HRQOL scores for the majority of patients are fairly consistent across multiple disease states. Certain disease states have been shown to have worse HRQOL scores and survival as compared to other etiologies [10]. Specific diseases that have shown worse survival outcomes include Hepatitis C virus (HCV) infection and patients who resume drinking following transplant [10]. Patients with HCV cirrhosis that have received a transplant have worse HRQOL scores if the disease recurs post-transplant [10]. Interestingly, the data is conflicted on patients without recurrence of HCV but most studies report a favorable outcome for patients who do not have recurrence of disease in comparison to those who do [7, 10]. Hepatitis B virus infection-related transplant does not have the same drop in HRQOL scores related to disease recurrence and has similar scores to other etiologies of liver transplantation [7, 10] because the rate of recurrence following transplant is less than 5 % when proper post-transplant procedure is followed [48]. Patients who resume alcohol post-transplant also have shown a significant drop in HRQOL scores [49]. Indefinite exposure to immunosuppression and the complications , such as infections, associated with long-term immunosuppression has also been identified as a factor that has led to significant drops in HRQOL scores and even life expectancy [50, 51]. Another less studied factor that leads to drops in HRQOL scores is gender [10]. Women report lower HRQOL scores in comparison to men in most studies following liver transplantation, and the reason for lower scores seen is not well understood but most studies point to psychological or social factors [10]. Other factors that lead to poor HRQOL are less well studied, and as patient survival continues to be longer, more factors will emerge and should be monitored.

Risk assessment of retransplant candidates follows a similar algorithm of risk assessment for first-time transplant candidates [52, 53]. Patients with graft failure within 1–2 weeks after transplantation are granted a more urgent status unlike graft failures outside this window [52]. This is an important difference in risk assessment because patients outside this window are assessed as less urgent and basically start over in the process as opposed to patients in this window [52]. Retransplant candidates are stratified according to their MELD score, and it has been reported that the MELD score may not be as accurate in patients awaiting retransplant [52]. Current MELD allocation rules also have not been shown to significantly change the rate of death for patients awaiting a retransplant or a primary transplant [54]. Other factors that impact whether a c andidate is listed for retransplantation include ethical, clinical, and potentially financial concerns.

Liver transplantation in a patient with a prior liver transplant is a controversial subject with ethical, technical, and financial considerations. Four major concepts in medical ethics are patient autonomy, beneficence, non-maleficence, and justice [52, 55] (Table 17.1). These principles form the ethos that guide a physician to perform the best individualized care for patients. Liver retransplantation represents a very complex conundrum for which there is no easy or simple answer. When a patient’s graft has reached graft failure, the only available treatment for that patient is retransplantation, but liver grafts are an extremely valuable and scarce resource. Long-term survival after liver retransplantation is not guaranteed, and all-cause liver retransplantation is in fact associated with inferior survival rates when compared to primary liver transplantation [6]. Further retransplantation, a third or greater number of retransplantation, shows even lower survival rates [6]. A single-center study showed a 1-year survival rate of a fourth liver retransplant of 31 % [56]. Thus, the argument that a patient who requires a second or greater liver transplant is not any more deserving than a patient seeking a primary liver transplant has been made and is a serious consideration in the setting of scarce resources [52, 57]. While this argument is theoretically sound, this is not an acceptable explanation for many patients who need a retransplant. Also complicating the matter is the bond that forms between patient and physician. This makes the decision to not implement lifesaving therapy due to a number when clearly the benefits outweigh the risks to the patient very difficult. As currently there is no clear standard on how to treat such patients [52], clinical judgment and a multidisciplinary team approach allow for the burden to be distributed.