Meta-analysis and meta-regression of outcomes for adult living donor liver transplantation versus deceased donor liver transplantation

Prior single center or registry studies have shown that living donor liver transplantation (LDLT) decreases waitlist mortality and offers superior patient survival over deceased donor liver transplantation (DDLT). The aim of this study was to compare outcomes for adult LDLT and DDLT via systematic review. A meta-analysis was conducted to examine patient survival and graft survival, MELD, waiting time, technical complications, and postoperative infections. Out of 8600 abstracts, 19 international studies comparing adult LDLT and DDLT published between 1/2005 and 12/2017 were included. U.S. outcomes were analyzed using registry data. Overall, 4571 LDLT and 66,826 DDLT patients were examined. LDLT was associated with lower mortality at 1, 3, and 5 years posttransplant (5-year HR 0.87 [95% CI 0.81–0.93], p < .0001), similar graft survival, lower MELD at transplant (p < .04), shorter waiting time (p < .0001), and lower risk of rejection (p = .02), with a higher risk of biliary complications (OR 2.14, p < .0001). No differences were observed in rates of hepatic artery thrombosis. In meta-regression analysis, MELD difference was significantly associated with posttransplant survival (R² 0.56, p = .02). In conclusion, LDLT is associated with improved patient survival, less waiting time, and lower MELD at LT, despite posing a higher risk of biliary complications that did not affect survival posttransplant.     

Pediatric living donor liver transplantation with large‐for‐size left lateral segment grafts

Usage of “large‐for‐size” left lateral segment (LLS) liver grafts in children with high graft to recipient weight ratio (GRWR) is controversial due to concerns about increased recipient complications. During the study period, 77 pediatric living donor liver transplantations (LDLTs) with LLS grafts were performed. We compared recipients with GRWR ≥2.5% (GR‐High = 50) vs GRWR <2.5% (GR‐Low = 27). Median age was higher in the GR‐Low group (40 vs 8 months, P> .0001). Graft (GR‐High: 98%, 98%, 98% vs GR‐Low: 96%, 93%, 93%) and patient (GR‐High: 98%, 98%, 98% vs GR‐Low: 100%, 96%, 96%) survival at 1, 3, and 5 years was similar between groups (P = NS). Overall complications were also similar (34% vs 30%; P = .8). Hepatic artery and portal vein thrombosis following transplantation was not different (P = NS). Delayed abdominal fascia closure was more common in GR‐High patients (17 vs 1; P = .002). Subgroup analysis comparing recipients with GRWR ≥4% (GR‐XL = 20) to GRWR <2.5% (GRWR‐Low = 27) revealed that delayed abdominal fascia closure was more common in the GR‐XL group, but postoperative complications and graft and patient survival were similar. We conclude that pediatric LDLT with large‐for‐size LLS grafts is associated with excellent clinical outcomes. There is an increased need for delayed abdominal closure with no compromise of long‐term outcomes. The use of high GRWR expands the donor pool and improves timely access to the benefits of transplantation without extra risks.     

Psychological Outcomes of Living Liver Donors From a Multicenter Prospective Study: Results From the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL‐2)

Although single‐center and cross‐sectional studies have suggested a modest impact of liver donation on donor psychological well‐being, few studies have assessed these outcomes prospectively among a large cohort. We conducted one of the largest, prospective, multicenter studies of psychological outcomes in living liver donors within the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study2 (A2ALL‐2) consortium. In total, 271 (91%) of 297 eligible donors were interviewed at least once before donation and at 3, 6, 12, and 24 mo after donation using validated measures. We found that living liver donors reported low rates of major depressive (0–3%), alcohol abuse (2–5%), and anxiety syndromes (2–3%) at any given assessment in their first 2 years after donation. Between 4.7% and 9.6% of donors reported impaired mental well‐being at various time points. We identified significant predictors for donors’ perceptions of being better people and experiencing psychological growth following donation, including age, sex, relationship to recipient, ambivalence and motivation regarding donation, and feeling that donation would make life more worthwhile. Our results highlight the need for close psychosocial monitoring for those donors whose recipients died (n=27); some of those donors experienced guilt and concerns about responsibility. Careful screening and targeted, data‐driven follow‐up hold promise for optimizing psychological outcomes following this procedure for potentially vulnerable donors.     

Understanding family dynamics in adult-to-adult living donor liver transplantation decision-making in Taiwan: Motivation,communication, and ambivalence

This study investigated how multiple family members co-construct the ethical significance of living donor liver transplantation (LDLT) and how the family structure and dynamics of donor–recipient–caregiver relationships shape the communication and decision-making process within the sociocultural context of Taiwan. We conducted in-depth interviews with 36 participants from 13 families at the Chang Gung Memorial Hospital from February to December 2019. Interviews were audio recorded, transcribed, and translated from Mandarin to English and analyzed utilizing grounded theory and thematic analysis. Our findings revealed that LDLT in Taiwan is not merely a personal choice of either donor or recipient but essentially a collaborative process of family-centered medical decision-making, intertwined with socioeconomic conditions, cultural and social norms, gender roles, and the division of labor in the household. The notion of reciprocity and indebtedness for family members is a central theme underlying the entire process of motivation, deliberation, and decision-making, thereby reinforcing the naturalness of LDLT. However, our study highlighted that donors from families with traditional gender hierarchy and power imbalance may experience psychological and social vulnerabilities. Conclusively, we suggest that healthcare professionals should be sensitive to the contextual and relational factors involved in family dynamics and provide appropriate support to the ambivalent donors.     

The Long‐Term Follow‐up and Support for Living Organ Donors: A Center‐Based Initiative Founded on Developing a Community of Living Donors

Transplant professionals recognize that the long‐term follow‐up of living organ donors is a priority, yet there has been no implemented solution to this problem. This critical gap is essential, because the transplant field is now emphasizing living donation as a means to address the organ shortage. We detail our living donor initiative, which sets several priorities we recognize as fundamental to persons who have donated organs at our transplant center. This intervention attempts to mitigate the donor and center factors that are known to contribute to the lack of long‐term follow‐up. Beyond that, our goals are aimed at providing ongoing engagement, wellness, clinical data accrual, laboratory follow‐up, and social support for our living donors, in continuity. Our ultimate goal is to nurture the development of local living donor community networks by providing social engagement for current and past donors, which also serves as a platform for greater population education on the societal importance of living donation. This initiative is based on joint recognition by our transplant team and our hospital leadership that supporting the long‐term welfare of living donors is essential to accomplishing the goal of expanding living donor transplantation. The transplant team and hospital missions are aligned, and both contribute resources to the initiative.     

Living donor liver paired exchange: A North American first

Paired organ exchange can be used to circumvent living donor-recipient ABO incompatibilities. Herein, we present the first case of successful liver paired exchange in North America. This 2-way swap required 4 simultaneous operations: 2 living donor hepatectomies and 2 living donor liver transplants. A nondirected anonymous living donor gift initiated this domino exchange, alleviating an ABO incompatibility in the other donor-recipient pair. With careful attention to ethical and logistical issues, paired liver exchange is a feasible option to expand the donor pool for incompatible living liver donor-recipient pairs.     

Expanding living donor liver transplantation: Report of first US living donor liver transplant chain

Living donor liver transplantation (LDLT) enjoys widespread use in Asia, but remains limited to a handful of centers in North America and comprises only 5% of liver transplants performed in the United States. In contrast, living donor kidney transplantation is used frequently in the United States, and has evolved to commonly include paired exchanges, particularly for ABO-incompatible pairs. Liver paired exchange (LPE) has been utilized in Asia, and was recently reported in Canada; here we report the first LPE performed in the United States, and the first LPE to be performed on consecutive days. The LPE performed at our institution was initiated by a nondirected donor who enabled the exchange for an ABO-incompatible pair, and the final recipient was selected from our deceased donor waitlist. The exchange was performed over the course of 2 consecutive days, and relied on the use and compliance of a bridge donor. Here, we show that LPE is feasible at centers with significant LDLT experience and affords an opportunity to expand LDLT in cases of ABO incompatibility or when nondirected donors arise. To our knowledge, this represents the first exchange of its kind in the United States.     

Dual‐graft adult living donor liver transplantation with ABO‐incompatible graft: short‐term and long‐term outcomes

ABO‐incompatible (ABOi) dual‐graft (DG) adult living donor liver transplantation (ALDLT) is not commonly performed due to its inherently intricate surgical technique and immunological complexity. Therefore, data are lacking on the short‐ and long‐term clinical outcomes of ABOi DG ALDLT. We performed a retrospective study by reviewing the medical records of patients who underwent ABOi DG ALDLT between 2008 and 2014. Additionally, computed tomography volumetric analysis was conducted to assess the graft regeneration rate. The mean age of a total of 28 recipients was 50.2 ± 8.5 years, and the mean model for end‐stage liver disease score was 12.2 ± 4.6. The 1‐, 3‐, and 5‐year patient survival rate was 96.4% during the mean follow‐up period of 57.0 ± 22.4 months. The 1‐, 3‐, and 5‐year graft survival rate was 96.4%, 94.2%, and 92.0%, respectively, and no significant differences were observed between ABO‐compatible (ABOc) and ABOi grafts (P = .145). The biliary complication rate showed no significant difference (P = .195) between ABOc and ABOi grafts. Regeneration rates of ABOi grafts were not significantly different from those of ABOc grafts. DG ALDLT with ABOi and ABOc graft combination seems to be a feasible option for expanding the donor pool without additional donor risks.     

Social and Financial Outcomes of Living Liver Donation: A Prospective Investigation Within the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL‐2)

Because results from single‐center (mostly kidney) donor studies demonstrate interpersonal relationship and financial strains for some donors, we conducted a liver donor study involving nine centers within the Adult‐to‐Adult Living Donor Liver Transplantation Cohort Study 2 (A2ALL‐2) consortium. Among other initiatives, A2ALL‐2 examined the nature of these outcomes following donation. Using validated measures, donors were prospectively surveyed before donation and at 3, 6, 12, and 24 mo after donation. Repeated‐measures regression models were used to examine social relationship and financial outcomes over time and to identify relevant predictors. Of 297 eligible donors, 271 (91%) consented and were interviewed at least once. Relationship changes were positive overall across postdonation time points, with nearly one‐third reporting improved donor family and spousal or partner relationships and >50% reporting improved recipient relationships. The majority of donors, however, reported cumulative out‐of‐pocket medical and nonmedical expenses, which were judged burdensome by 44% of donors. Lower income predicted burdensome donation costs. Those who anticipated financial concerns and who held nonprofessional positions before donation were more likely to experience adverse financial outcomes. These data support the need for initiatives to reduce financial burden.     

Long‐Term Medical and Psychosocial Outcomes in Living Liver Donors

Due to the enduring organ shortage, living donor liver transplantation has been a valuable treatment strategy for advanced liver disease patients for over 20 years. A variety of reviews have summarized the extensive data now available on medical and psychosocial risks to living donors in the aftermath of donation. However, evidence on donor medical and psychosocial outcomes beyond the first year postdonation has not been synthesized in any previous review. The evidence base on such “long‐term” outcomes has been growing in recent years. A review of this evidence would therefore be timely and could serve as an important resource to assist transplant centers in their efforts to fully educate prospective donors and gain informed consent, as well as develop appropriate postdonation clinical care and surveillance plans. We reviewed recent literature on long‐term donor outcomes, considering (a) medical outcomes, including mortality risk, rates of complications, abnormalities detected in laboratory testing, and the progress of liver regeneration; and (b) donor‐reported psychosocial outcomes reflecting physical, emotional, and interpersonal/socioeconomic well‐being, as well as overall health‐related quality of life. We summarize limitations and gaps in available evidence, and we provide recommendations for future research and clinical care activities focused on long‐term outcomes in liver donors.     

Pure laparoscopic living donor liver transplantation: Dreams come true

Minimally invasive approaches are increasingly being applied in surgeries and have recently been used in living donor hepatectomy. We have developed a safe and reproducible method for minimally invasive living donor liver transplantation, which consists of pure laparoscopic explant hepatectomy and pure laparoscopic implantation of the graft, which was inserted through a suprapubic incision. Pure laparoscopic explant hepatectomy without liver fragmentation was performed in a 60-year-old man with alcoholic liver cirrhosis and hepatocellular carcinoma. The explanted liver was retrieved through a suprapubic incision. A modified right liver graft, procured from his 24-year-old son using the pure laparoscopic method, was inserted through a suprapubic incision, and implantation was performed intracorporeally throughout the procedure. The time required to remove the liver was 369 min, and the total operative time was 960 min. No complications occurred during or after the surgery. The patient recovered well, and his hospital stay was of 11 days. Pure laparoscopic living donor liver transplantation from explant hepatectomy to implantation was performed successfully. It is a feasible procedure when performed by a highly experienced surgeon and transplantation team. Further studies with larger sample sizes are needed to confirm its safety and feasibility.

     

Long‐Term Non–End‐Stage Renal Disease Risks After Living Kidney Donation

Despite generally positive outcomes and high rates of satisfaction, living kidney donors are at risk for both medical and psychosocial problems. In this review, the authors summarize non–end‐stage renal disease (ESRD) risks for donors and describe limitations to the data. We review the evidence of medical risks (e.g. increased cardiovascular disease and mortality, preeclampsia) and psychosocial risks (e.g. mood disturbance, financial burden). We then discuss the evidence of differential risks among subsets and the impact of postdonation events (e.g. development of diabetes). Collectively, available evidence indicates the following. (1) Recognizing the importance of non‐ESRD risks has been overshadowed by analyses of the reported risk of ESRD. This imbalance should be remedied. (2) There is little quantification of the true contribution of donation to medical and psychosocial outcomes. (3) Most studies, to date, have been retrospective, with limited sample sizes and diversity and with less‐than‐ideal controls for comparison of outcomes. (4) Many postdonation events (diabetes and hypertension) can now be reasonably predicted, and their association with adverse outcomes can be quantified. (5) Mechanisms and systems need to be implemented to evaluate and care for donors who develop medical and/or psychosocial problems. (6) Costs to donors are a significant burden, and making donation financially neutral should be a priority.     

Impact of graft thickness reduction of left lateral segment on outcomes following pediatric living donor liver transplantation

Reducing graft thickness is essential to prevent large‐for‐size graft problems in pediatric living donor liver transplantation (LDLT). However, long‐term outcomes of LDLT using reduced‐thickness left lateral segment (LLS) grafts are unclear. In 89 patients who underwent LDLT using reduced LLS grafts between 2005 and 2017, short‐term and long‐term outcomes were compared between a nonanatomically reduced LLS (NAR‐LLS) graft group and a reduced‐thickness LLS graft group. Estimated blood loss was lower and abdominal skin closure was less needed in the recipient operation in the reduced‐thickness LLS graft group. Postoperatively, portal vein (PV) flow was significantly decreased in the NAR‐LLS graft group, and there was shorter intensive care unit (ICU) stay and fewer postoperative complications, especially bacteremia, in the reduced‐thickness LLS graft group. Graft survival at 1 and 3 years after LDLT using reduced‐thickness LLS grafts was 95.2% and 92.4%, respectively, which was significantly better than for NAR‐LLS grafts. Multivariate analysis revealed that fulminant liver failure, hepatofugal PV flow before LDLT, and NAR‐LLS graft were associated with poor graft survival. In conclusion, LDLT using reduced‐thickness LLS grafts is a safe and feasible option with better short‐ and long‐term outcomes in comparison with NAR‐LLS grafts.     

Health-related quality of life after anonymous nondirected living liver donation: A multicenter collaboration

Literature on living nondirected liver donation is sparse. The purpose of this study was to assess health-related quality of life (HR-QOL) in anonymous nondirected living liver donors (ND-LLDs). ND-LLDs at 3 centers: University of Alberta (n = 12), University of Colorado (n = 12), and University of Southern California (n = 12), were surveyed. Thirty donors (83%) responded to the Donor Quality of Life (USC DQLS) and Short-Form 36 (SF-36). Most respondents (n = 15, 50%) donated their left lateral segment, 27% right lobe, and 23% left lobe. The majority were female (67%) and mean age was 38.9 ± 11.2 years at donation. Median follow-up was 1.1 (interquartile range 0.4-3.3) years. Approximately 37% had previously donated a kidney. Eleven experienced ≥1 postoperative complication, with only 1 Clavien-Dindo IIIb. Most reported minimal impact on school or work performance, all felt positive or neutral about their overall health since donation, and none expressed postdonation regrets. No donor reported impacts on health insurability, and 3 of 4 respondents attempting to purchase life insurance postdonation were successful. ND-LLD SF-36 outcomes were similar to US population norms. Overall, ND-LLDs demonstrated acceptable HR-QOL after donation and are appropriate candidates for partial liver donation. Based on evaluation of donation impact, consideration should be given to postdonation support strategies.     

Peptic Ulcer Disease in Living Liver Donors: A Longitudinal Population‐Based Study

The objective of this nationwide cohort study was to investigate the risk of peptic ulcer disease (PUD) in living liver donors (LDs). A total of 1333 LDs and 5332 matched nondonors were identified during 2003–2011. Hospitalized patients identified as LDs were assigned to the LD cohort, and the non‐LD comparison cohort comprised age‐ and sex‐matched nondonors. Cumulative incidences and hazard ratios (HRs) were calculated. The overall incidence of PUD was 1.74‐fold higher in the LD cohort than in the non‐LD cohort (2.14 vs. 1.48 per 1000 person‐years). After adjustment for age, sex, monthly income and comorbidities, we determined that the LD cohort exhibited a higher risk of PUD than did the non‐LD cohort (adjusted HR 1.74, 95% confidence interval [CI] 1.45–2.09). The incidence of PUD increased with age; the risk of PUD was 2.53‐fold higher in patients aged ≥35 years (95% CI 2.14–2.99) than in those aged ≤34 years. LDs with comorbidities of osteopathies, chondropathies and acquired musculoskeletal deformities exhibited a higher risk of PUD (adjusted HR 3.93, 95% CI 2.64–5.86) compared with those without these comorbidities. LDs are associated with an increased risk of PUD after hepatectomy.     

Robotic donor hepatectomy: A major breakthrough in living donor liver transplantation

Living donation in many countries is the main resource of organs. Healthy, volunteering individuals deserve the highest safety standards possible in addition to the least invasive technique to procure the organs. Since the introduction of living donor liver transplantation, many efforts have been made to minimize the surgical trauma inherent to living donor surgery. The journey started with a large Mercedes incision and evolved to reverse L-shaped and small upper midline incisions before the introduction of minimally invasive laparoscopic techniques originated. The technical difficulties of the laparoscopic approach due to suboptimal instrumentation, challenging ergonomics, and the long learning curve limited the application of the fully laparoscopic approach to a few centers. The recent introduction of the robotic platform with its superb optical system and advanced instruments allows for the first time, a genuine emulation of open donor surgery in a closed abdomen, thus allowing all liver donors to benefit from minimally invasive surgery (better cosmesis, less pain and morbidity, and better quality of life) without compromising donor safety. This attribute in combination with the ubiquitous presence of the robot in major transplant centers may well lead to the desired endpoint of this technology, namely, the widespread dissemination of minimally invasive donor surgery.