EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Living-donor liver transplant represents an established alternative to deceased-donor liver transplant. The procedure is considered safe for donors; however, concerns about the donors’ health-related quality of life and health status have not been fully addressed. Here, we aimed to assess the health-related quality of life and postoperative and 1-year clinical outcomes in living liver transplant donors.

Materials and Methods: All patients undergoing liver resection for adult-to-adult living-donor liver trans-plant at our center between December 1999 and March 2013 were evaluated retrospectively. Health-related quality of life was evaluated in a second assessment through written health-related quality of life questionnaires (the Short Form 36 assessment tool) sent to all patients who underwent liver resection for living-donor liver transplant between 1989 and 2012.

Results: We identified 104 patients who underwent liver resection for living-donor liver donation between December 1999 and March 2013. Postoperative morbidity was 35.9%, with 56.8% of patients having minor complications. No postoperative, 30-day, or 90-day mortality was evident. At year 1 after transplant, 30 patients (28.8%) had (ongoing) complications, of which 80% were considered minor according to Clavien-Dindo classification. Regarding health-related quality of life, liver donors were characterized as having significantly higher scores in the general health perception component in the Short Form 36 assessment tool (P < .001). We found no significant results in other assessment components (all P > .05).

Conclusions: Liver donors are characterized by an excellent health-related quality of life that is comparable to the general population. Because some donors tend to have concerns regarding their employment status after the procedure, a com-prehensive and critical evaluation of potential donors is needed.

Key words : Health status questionnaire, Postoperative morbidity, Short Form 36 assessment tool

Liver transplant is a life-saving therapy option for patients with end-stage liver disease. However, there is an increasing organ shortage, which has led to a compensatory rise in donations and transplants involving living donors.^1-3 Living-donor liver transplant (LDLT) can now be performed safely with even better outcomes for recipients than deceased-donor liver transplant. This is mainly due to reduced wait times, an often preoperatively well-evaluated quality of the living-donor organ, and a markedly shortened cold ischemia time during transplant.^4,5

Obvious benefits are however outweighed by the exposure of healthy donors to the risks of postoperative morbidity and even mortality.^6,7 Postoperative complications such as biliary leakage and morbidity related to the abdominal incision have been reported to occur in up to 15% and 19% of donors, respectively.^8,9 In addition to the known medical risks of donor liver resection, donations can affect the postoperative health-related quality of life (HRQoL) of donors; therefore, this is viewed as an important aspect of donor outcome and thus preoperative education. This outcome parameter is of particular importance because the living donor has no medical advantages from LDLT and only has the potential benefit of knowledge of having saved a life.

Several studies have investigated the HRQoL after LDLT and have shown that physical well-being decreases during the immediate postoperative period but returns to levels of the general population within 1 year after donation, whereas the mental well-being appears to be stable during this process.^10-13 Parameters such as the graft type (left or right lobe), donor age, the urgency of the recipient’s need for transplant, postoperative and other donor complications, and posttransplant recipient morbidity and mortality were also identified as possible important negative predictive parameters for a poor HRQoL in donors.14-16 However, most studies have been limited by their small sample size, a retrospective single-center study design, and a lack of a standardized assessment of donor HRQoL parameters. Therefore, we performed this study to evaluate both the postoperative morbidity and the short- and long-term influences of LDLT on the HRQoL of donors, as assessed by the established standardized Short Form 36 (SF-36) outcome measurement tool.¹⁷

Materials and Methods

Study design and patient selection
All patients who underwent liver resection for adult-to-adult LDLT at our Department of Surgery (Campus Virchow-Klinikum, Charité-Universitätsmedizin, Berlin, Germany) between December 1999 and March 2013 were evaluated retrospectively using an established database. The donors were analyzed according to type of operation (left or right hemihepatectomy).

Health-related quality of life was evaluated in a second assessment through written HRQoL questionnaires (SF-36) sent to all patients who underwent liver resection for living liver donation between 1989 and 2012. With these questionnaires, a short general questionnaire was sent to the patients via mail. We allowed 2 weeks for return of the completed questionnaires. Because the HRQoL assessment was performed separately, it was not possible to correlate HRQoL scores with clinical data.

Living liver donors who were older than 18 years and had full medical history available were included in our study. Patients who were not able to understand and read and write German were excluded. Written informed consent for surgery and use of clinical data were obtained from all patients, as required by our institutional review board. This study was performed in accordance with the Declaration of Helsinki and its amendments and was approved by the institutional ethics committee.

Follow-up
All patients were seen and examined twice during follow-up (at 6 and 12 months postoperatively).

Clinical data
Clinical data analyzed retrospectively included demographic data, such as age, sex, and degree of relationship with liver transplant recipient. Both perioperative complications and complications that occurred or were still present during the follow-up examinations were included and categorized as follows: biliary (bile leak, cholangitis, cholestasis, papillary stenosis), abdominal (bleeding, delayed gastric emptying, wound dehiscence and wound infection, incision pain/itching, incisional hernia), cardiopulmonary (pneumothorax, pleural effusion, pleuritic, pleural empyema), hepatic (ascites, transient perfusion disorder, partial hepatic vein thrombosis, transient liver failure), infections (bacterial, viral, fungal), and other complications. We classified these complications using a modified Clavien-Dindo system, where grade 0 indicated no surgical complication; grade I indicated surgical complications needing conservative treatment, repeat controls, or bedside therapy; grade II indicated surgical complications needing invasive interventions; and grade III indicated multiorgan failure and death.

Grade I complications were considered minor and grade II and III complications were considered major complications. Moreover, we assessed the need for interventions such as endoscopic retrograde cho-langiopancreatography, redo surgery, and computed tomography-targeted drainage. For follow-up, medical records were analyzed.

We classified the relationship between donors and recipients as follows: grade 1 indicated mother, father, son, or daughter; grade 2 indicated brother, sister, grandmother, grandfather, grandson, or granddaughter; grade 3 indicated great-grandfather, great-grandmother, great-grandson, great-grand-daughter, aunt, uncle, nephew, or niece; and grade 4 indicated great-great-grandfather, great-great-grandmother, great-great-grandson, great-great-granddaughter, or cousin.

Assessment of health-related quality of life using the Short Form 36
The SF-36 is a tool to measure HRQoL of patients who are over 14 years old.17 The questionnaire includes 36 questions about current health situation. There are 8 dimensions of HRQoL, which can be divided into 2 categories: the physical component summary and mental component summary.

The physical component summary contains the following subscales: physical functioning (10 items), role-physical (4 items), bodily pain (2 items), and general health perception (6 items). The mental component summary includes the scales vitality (4 items), social functioning (2 items), role-emotional (3 items), and mental health (5 items). In each scale, the possible scores range from 0 to 100 points, with 0 representing the lowest score and 100 representing the highest score.

Statistical analyses
Data collection and analyses were performed using Microsoft Excel (Microsoft, Redmond, WA, USA) and SPSS (SPSS: An IBM Company, version 22.0, IBM Corporation, Armonk, NY, USA). We tested normality using the Kolmogorov-Smirnoff test. Because results showed no Gaussian distribution, we used nonparametric tests for statistical analysis of continuous variables (Mann-Whitney U test and Kruskal-Wallis test). Continuous variables are shown as mean and standard deviation. Categorical variables were compared using the chi-square-test. All variables with P < .05 were considered to be statistically significant.

Patient characteristics
In total, 104 patients who underwent liver resection for living liver donation were identified, with 44 female (42.3%) and 60 male patients (57.7%) having mean (SD) age of 49.8 (12.2) years. Except for 1 patient (1.0%), who required a left lateral segmentectomy (segments II and III), all patients underwent right hemihepatectomy (liver segments V-VIII). Regarding the relationships between donors and recipients, most patient-donor groups had grade 1 relationships (41 donors, 39.8%). Of 39 donors (37.9%) who had no biologic relationship with the recipient, there were 32 spouses of the recipients (31.1%). Table 1 shows the baseline characteristics.

Postoperative complications
In our patient group, 37 donors (35.9%) had com-plications, with 21 (56.8%) having minor compli-cations (grade I per modified Clavien-Dindo system, Table 2). Grade II complications were observed in 16 patients (43.2%), and no patient had a grade III complication. Postoperative mortality was 0 (see Table 2 for a detailed overview of all postoperative complications). In 4 donors (3.9%), computed tomography-guided drainage of an intra-abdominal liquid collection was necessary; in 6 patients, an endoscopic retrograde cholangiopancreatography had to be performed. Redo surgery of any kind was needed in 7 patients (6.8%).

Follow-up and midterm outcomes
Follow-up data were available for all patients. During the 1-year follow-up after liver resection, 30 patients (31.2%) had (ongoing) complications of which 24 (82.8% of all patients and 23.3% of patients with complications) were considered minor (grade I using a modified Clavien-Dindo system) and 6 (20% of all patients with complications, 6.2% of all patients) were considered major (grade II). Of the 6 patients with complications considered as grade II, 2 (40%) had an uneventful postoperative course, 2 (40%) had grade I complications, 1 patient had grade II complications during the postoperative course, and 1 patient had grade II complications during follow-up. There were no grade III complications or deaths during follow-up. Table 3 summarizes morbidity during follow-up.

Health-related quality of life
Between 1989 and 2012, 133 living liver transplant procedures were performed. For HRQoL assessment, 7 patients (5.3%) had to be excluded (1 due to cognitive deficits and 6 because they were living abroad). Of these 126 donors, there were 39 (31.0%) eligible SF-36 questionnaires. The donors who had returned the SF-36 questionnaires had a mean age of 42 years (range, 26-63 y). There were 28 women (71.8%) and 11 men (28.2%). Mean time (SD) after transplant was 113 (41) months (range, 7-161 mo; Figure 1). The general questionnaire was answered by 47 patients (15 men, 32% and 32 women, 68%; Table 4).

Concerning the SF-36 results, the matched sample from the general population consisted of 2914 individuals. With regard to general health perception, donors had significantly higher scores (P < .001; Figure 1). The remaining dimensions, including the summation scores, did not differ significantly between both groups (physical functioning: P = .263, role-physical: P = 0.421, vitality: P = .245, social functioning: P = .245, role-emotional: P = .538, mental health: P = .334).

In the present study, we found an acceptably low rate of postoperative complications in patients who underwent liver resection for LDLT. Most complications were minor with no need for any intervention. Health-related quality of life scores were excellent and comparable to a representative sample from the general population. Moreover, liver donors had significantly higher scores in the general health perception component.

Numerous studies have examined the peri-operative outcomes of hepatectomy procedures for liver donation. Overall, morbidity ranges between 17% and 40% in most analyses.^18-27 Major complications appear in 2% to 13% of cases. This is in line with the findings of the present analysis where we found a 36% complication rate, with most of these patients having minor complications and approximately 5% of all patients having major (grade II) complications. Male sex, high body mass index, remnant liver volume of ≤ 32.50%,²⁸ prolonged operative time (> 400 min), intraoperative hypo-tension (systolic < 100 mm Hg), vascular abnor-malities, and intraoperative blood loss (> 300 mL)⁸ were found to be associated with major com-plications. Cardiopulmonary adverse events, mainly pleural effusions, have been reported to occur in about 9% to 20% of cases.^20,22 In our study, cardiopulmonary complications appeared in 9% and biliary complications in 11% of all patients. Of the biliary complications, the largest proportion was the occurrence of bile leaks (9%). In a series of 553 consecutive patients, Dirican and colleagues found a similar rate of biliary complications (9%), with most patients in the study receiving a right hemihepatectomy.²¹ The Candido group reported a 23% rate of bile leaks and found significantly more biliary complications among patients with a history of right hemihepatectomy.²³ A large multicenter analysis of more than 5000 patients revealed a relatively low rate of biliary complications (3%); the rate of overall and major complications was significantly lower in high-volume centers (> 100 hepatectomies) compared with low-volume centers.²⁹ Because of the heterogeneity of definitions in the literature, the true incidence of bile leak complications is difficult to assess.³⁰

With regard to long-term health problems, most of our patients had minor complaints (eg, minor scar problems). These findings are in line with the present literature.^22,24,31 Abecassis and colleagues reported a 95% probability of complication resolution 1 year after donation. Incisional hernias and psychologic disorders were frequent problems during follow-up.32 Nonetheless, the comparison of results is difficult because the percentage of patients who were analyzed was low32; moreover, complications that occurred during follow-up are not always clearly mentioned or not assessed at all.^18,20

Regarding HRQoL, we found excellent scores for living donors that were comparable to the scores shown in the general population. In the general health component, donors had even higher scores than the reference population. The current literature provides several studies examining HRQoL in liver donors, in which the number of patients ranged between 22 and 127.^13,14,33-41 The SF-36 is the most frequently used tool for measurement of HRQoL, and the scores are comparable to the findings in our present study.^34-37,40,41 Compared with the HRQoL shown in the general population, liver donors had equal scores in most examinations.^35,37,41 However, some studies found decreased physical and psychologic scores postoperatively.³³ The physical aspects of HRQoL appear to be especially decreased in the early postoperative period.^13,36,37 Further risk factors for an impairment of the donors’ HRQoL are the death of the recipient34 and predonation concerns and time to donation > 4 weeks.³⁵ Regarding the influence of postoperative complications on HRQoL, there are controversial findings.^14,40,41 Our results suggest that some donors have problems concerning their work life and employment status post-operatively, which is in line with findings from other studies.^12,39

A limitation of this examination is the cross-sectional HRQoL evaluation, which does not allow assessment of HRQoL over time. A preoperative evaluation would have been interesting. Furthermore, it was not possible to correlate HRQoL results to clinical outcome variables such as postoperative complications since the survey was performed separately for the clinical evaluation. Moreover, the number of returned questionnaires was relatively small, which could suggest an underlying selection bias. Nonetheless, this study not only includes relevant information on both living conditions and HRQoL but also on clinical data. Concerning the clinical aspects, we included a vast and a representative number of patients and clinical parameters. However, further studies, in particular on the development of HRQoL over time, are urgently needed to draw final conclusions on this topic.

Living liver donation can be safely performed and showed low major complication rates during the postoperative course and during follow-up. Liver donors are found to have an excellent HRQoL that is comparable to that shown in the general population. However, a comprehensive and critical evaluation of potential donors is essential. Regular follow-up examinations are thus needed to detect and treat medical conditions that are associated with liver donation.

Volume: 16 Issue: 5 October 2018

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