Primary liver transplantation and liver retransplantation: comparison of health-related quality of life and mental status – a cross-sectional study

Orthotopic Liver Transplantation (LT) is the only curative treatment for an end-stage liver disease (ESLD), as well as for an acute liver failure (ALF) and a non-resectable hepatocellular carcinoma. This well-established procedure has acceptable long-term outcomes with the overall survival of patients at 71% after 5 years. Nonetheless, graft survival is lower at 64% [1]. Thus, a considerable proportion of patients need to undergo an orthotopic Liver Retransplantation (Re-LT) after their first LT. Today, around 10% of all LT procedures are Re-LTs. Indications for an Re-LT are mostly due to primary nonfunction, venous thrombosis (early graft failure), ischemic type biliary lesions (ITBL) and a recurrence of the initial disease (late graft failure) [2, 3]. For improvements in the overall survival rates raises the likelihood for an Re-LT, as it increases the risks for a chronic graft failure or a recurrence of the primary disease [4, 5].

One of the major problems of Re-LT is the fact that the outcome of these patients is significantly decreased with significantly higher complication and hospitalisation rates compared to recipients of primary LT although Re-LT recipients often benefit from organs with a lower Donor Risk Index. Thus, it is suggested by some authors that a more optimal strategy of distributing organs should be established. This strategy should include restricting their use to patients who obtain a longer term benefit [6].

Besides a mere graft and patient survival, both the Health-Related Quality of Life (HRQoL) and the Mental Status have become an issue of further interest, as they are important outcome factors [7‐10]. It is well-known that transplantation improves the HRQoL, as well as the mental status, when compared to those patients on an LT waiting list [7, 11]. However, there are currently only a few examinations that have focused on these particular outcome variables among Re-LT recipients [9, 12‐14]. Since Re-LT is associated with an increased postoperative morbidity and a prolonged or insufficient recovery when compared to a primary LT, an impairment of the mental well-being and the HRQoL can be supposed [15].

Thus, the current study has sought to evaluate the HRQoL and the mental status of Re-LT recipients when compared to patients with a history of only one LT. Furthermore, the study aimed to investigate predictors that influence these outcome measures independent of the number of LTs.

The present study has shown that the Re-LT patients had significantly impaired HRQoL scores, with regards to their physical dimensions. Their mental status, including the anxiety and depression scores, did not differ significantly between the groups. We have shown that those patients who were suffering from a chronic kidney failure had decreased physical function scores, whereas the underlying liver disease had no impact on the results of both questionnaires.

Our group has previously reported good HRQoL and mental status scores among LT recipients when compared to the patients on the LT waiting list and the general population, respectively [7, 8]. In the current literature, there are numerous studies analysing the psychosocial factors in LT recipients [7, 15, 17, 18].

With regards to the results of the HADS survey, the anxiety and depression scores were lower than those in previous studies [7, 23, 24]. We have previously shown that the mental status (anxiety) of patients who underwent an LT was affected when compared to the general population [16]. Although not statistically significant, patients from the Re-LT group tended to have higher anxiety and depression scores, so there seems to be a further decrease in mental status after Re-LT. Since there are a few studies examining HRQoL but not mental status after Re-LT [9, 12, 13], the interpretation of our data in a greater context is difficult and speculative. Re-LT is associated with a higher rate of chronic graft failure [25]. Patients on the liver transplantation waiting list have who suffer from chronic liver disease were found to have higher levels of anxiety and depression when compared to LT recipients [8]. Some HRQoL studies include Re-LT patients [9, 12‐14]. However, in these examinations, there is no thorough analysis of this subgroup. Braun and colleagues mention a significant loss of HRQoL among Re-LT patients without further specification [13]. These findings are in line with our results. Although there is a considerable number of Re-LT patients each year, this patient group is completely underrepresented in HRQoL analyses. In most cases, a graft loss is due to a primary nonfunction or vascular thrombosis. About 8% of all LT recipients need to undergo a retransplantation [26, 27]. Clinical data has shown that both patient [26, 28, 29] and graft survival [2] are significantly reduced in Re-LT patients when compared to primary LT recipients. Re-LT is associated with an increased postoperative morbidity, including primary graft dysfunction, adult respiratory distress syndrome, infections, and acute renal failures, when compared to a primary LT [15]. This might be an explanation for the fact that there was a significant decrement in the HRQoL dimensions of PF, RP, VIT, and RE. An important aspect is the longevity of an LT, which is associated with a higher HRQoL [9]. For various reasons, such as the difficulties of redo surgery procedures, immunological problems after repeated organ transplantations, and a general poor health status at the time of the retransplantation, long-term graft survival is significantly impaired after an Re-LT [26, 30].

Montenevo have analysed a large cohort of Re-LT recipients and found that these patients were more likely to be on dialysis prior to transplant, hospitalized, in the intensive care unit, on a ventilator and had higher model for end-stage liver disease (MELD) while they had, on the other hand, lower Donor Risk scores when compared to primary LT recipients [6]. The authors state that higher quality grafts are used inefficiently in a sicker patient population and propose a more optimal strategy including restricting their use to patients who obtain a longer term benefit [6]. Although we have not analyzed the clinical course of the patients examined in the present study, the decrement, especially in HRQoL scores of Re-LT patients compared to primary LT patients underlines the need for an optimized organ distribution strategy. Our analysis further revealed that those patients who suffered from chronic kidney disease had lower PF scores compared to patient who patients who had not. These findings are in line with the current literature, HRQoL was found to be decreased in renal patients in the early stages of disease [31].

The comparison of our results with other studies is somewhat difficult, since there are no HRQoL studies on Re-LT patients. Nonetheless, our findings have indicated that patients who undergo an Re-LT, are at a risk of suffering from psychological disorders, as well as from an impaired HRQoL. As a consequence, a profound selection process of patients who are scheduled for an Re-LT has to be performed. One of the shortcomings is the cross-sectional design of this study. Additionally, the number of Re-LT patients was small. Since the response rate of the postal survey was 40%, there might be some selection bias which could possibly lead to the fact that only patients with either a extremely high or low HRQoL respond to the survey. Moreover, the interpretation of data is limited by the lack of clinical data such as performance status, the presence of ascites and icterus, and laboratory data since these factors are known to have an impact on physical status. Furthermore, the HRQoL data analysed in this examination are from two different surveys using different assessment methods. Since, it is known that different modes of HRQoL assessments lead to differing results [32]. Also, there is some potential time effect, since, as far as the group that was interviewed twice is concerned, only the most recent surveys (2013) were used for the comparisons. HRQoL might change over time and with increasing age, so this is a potential bias to our data. Although there were no statistically significant differences between the two assessments, these effects cannot completely be excluded. However, recent studies have only included Re-LT patients as a part of a bigger study collective without a closer examination of this subgroup. The present study is the first study to thoroughly focus on the HRQoL and the mental status in Re-LT patients. Moreover, we have established a matched control group, allowing for a good comparison of the results. Nevertheless, there is an urgent need for further studies, with larger sample sizes, in order to draw final conclusions on this topic.

Patients who have to undergo Re-LT procedures are facing a postoperative impairment, especially with the physical aspects of a HRQoL. Together with clinical results from other studies, the findings of the present examination underline the need for an optimized organ distribution strategy since not all patients listed for Re-LT appear to benefit from it.