Abstract
Background and aims
Many centers do not offer living donor transplants for patients in need of a liver retransplant. We aimed to study our liver retransplant outcomes using living donors and compared them with those of retransplants performed using deceased donors.
Methods
This study retrospectively analyzed all retransplants performed at our center between 2009 and 2023, and outcomes of living donor retransplants were compared with deceased donor retransplants using standard statistical tests.
Results
Between January 2009 and March 2023, a total of 77 retransplants, 60 with deceased donors and 17 with living donors, were performed. Important demographic differences between the two groups included a higher model for end-stage liver disease score in the deceased donor group (32.1 ± 6.1 vs. 19.4 ± 5.7, P < 0.001) and a higher number of early retransplants (within 3 months of the initial transplant), which accounted for 35% of deceased donor transplants but 0 of living donor transplants (P < 0.01). Overall, the patient and graft survival rates were comparable between the two groups. The patient survival rates at 1 and 3 years after transplant were 73% and 67% in the deceased donor group and 84% and 73% in the living donor group, respectively (P = 0.57). The hospital length of stay and blood product use were both better in the living donor group. Biliary complications did not show significant different between the two groups (P = 0.33).
Conclusions
Living donors can provide acceptable outcomes for those in need of a retransplant, with results comparable to those seen with deceased donors. A systematic approach to the patient in the pre-, peri-, and post-transplantation period is important in these complicated cases.
Keywords: Liver retransplant, Living donor liver transplant, Deceased donor, Outcomes, Complications
1. Introduction
Graft loss still occurs in 5%–22% of all liver transplants despite improvements in donor selection, organ procurement, surgical techniques, perioperative management, and immunosuppression.1, 2, 3 Liver retransplantation remains the treatment of choice for many of these patients. Approximately 8%–10% of liver transplants performed in the USA are retransplants, ranging from 7% to 17% from various centers.4, 5, 6, 7, 8, 9 Living donor liver transplantation is generally regarded as a good option for liver transplantation for many patients; however, very few retransplants are done with living donors. In fact, the majority of transplant centers in the USA regard a retransplant as a contraindication for the use of living donors. However, several studies from Asian centers have reported the use of living donors for retransplants.10,11 Because deceased donor transplants are usually not available at these centers, living donor transplants represent the only option for these patients.
Commonly, retransplantation (from a living or deceased donor) is associated with worse survival, a higher complication rate, and higher costs than primary transplantation.12, 13, 14, 15, 16, 17, 18 However, very few studies have compared the outcomes of living donor transplants with those of deceased donor transplants in these patients. Such a comparison would be important to determine whether outcomes with living donors would be acceptable in these situations and to adequately counsel patients in need of a retransplant regarding the options for transplantation. We hypothesize that outcomes with living donors would be acceptable in retransplants and not inferior to outcomes with deceased donors, as living donors offer several advantages over other options. Herein, we present our series of liver retransplantations using living donors and compare outcomes to retransplantation performed with deceased donors. An approach to the selection of living donors for liver retransplantations is presented.
2. Methods
2.1. Ethical approval
The study was approved by the Institutional Review Board of the University of Pittsburgh Medical Center Thomas E Starzl Transplant Research Registry, approval number 0307037. The study conforms to the ethical guidelines of the 2013 Declaration of Helsinki and abides by the 2018 Declaration of Istanbul. Informed consent was obtained from all patients (all donors and recipients) before enrollment in the registry.
2.2. Patient population
The study used the University of Pittsburgh Medical Center divisional database to perform a retrospective chart review on all liver transplant recipients who required retransplantation. Patients were divided into subgroups based on donor source: living vs. deceased donors. Only the first retransplants were included in the analysis because no cases of multiple retransplants were recorded in the living donor group. Demographic data including age at retransplant, race, and sex were collected. In addition, the hospital length of stay, model for end-stage liver disease (MELD) score, patient and graft survival with respective patient and graft survival days, primary etiology, operative time, blood transfusion requirements, need for renal replacement therapy, intensive care unit (ICU) length of stay, need for reoperation, and other surgical and medical complication details were obtained.
2.3. Operative procedure
Retransplants were performed using standard surgical techniques. Portal bypass was used for the majority of deceased donor transplants and all living donor transplants. Vascular conduits were used as needed, particularly in cases with previous vascular thrombosis. Biliary reconstruction for all living donor transplants was performed with hepaticojejunostomy.
2.4. Statistical analysis
Categorical variables were presented as numbers (percentages) and compared using a chi-squared test, whereas continuous variables were presented as means ± standard deviation and compared using Student's t-test. Patient and graft survival estimates and survival curves were obtained using Kaplan–Meier. A P-value <0.05 was considered significant. Statistical analyses were performed with IBM SPSS Statistics for Macintosh version 23.0 (IBM Corp., Armonk, NY, USA).
3. Results
3.1. Demographics of the participants
Between January 1, 2009, and March 31, 2023, using the Starzl Transplant Institute's Transplant Data Warehouse, 77 patients underwent liver retransplantation. Of these patients, 11 underwent retransplantation more than once, 78% (60/77) had deceased donor liver transplant, 22% (17/77) had living donors, and 9 were listed for a retransplant with deceased donors, but died before a retransplant could be done. All patients with suitable approved living donors received a retransplant. Basic demographics for the living and deceased donor groups are shown in Table 1. The major difference between the two groups was with their mean MELD score, which was 32.1 ± 6.1 in the deceased donor group versus 19.4 ± 5.7 in the living donor group (P < 0.001).
Table 1.
Demographics of the deceased and living donor transplant groups (N = 77).
| Characteristic | Deceased donor group (n = 60) | Living donor group (n = 17) | P-value |
|---|---|---|---|
| Recipient age (years) | 52.3 ± 10.6 | 48.8 ± 15.2 | 0.280 |
| Male, n (%) | 43 (72) | 10 (59) | 0.010 |
| MELD score | 32.1 ± 6.1 | 19.4 ± 5.7 | <0.001 |
| Cause for retransplant, n (%) | |||
| PNF or HAT | 21 (35) | 1 (6) | 0.010 |
| Recurrence | 24 (40) | 11 (65) | 0.010 |
| Time between the first and second transplant (months) | 25 (1–95) | 153 (127–169) | 0.005 |
| Early retransplant (within 3 months of the first transplant), n (%) | 21 (35) | 0 | <0.010 |
| Donor age (years) | 35.7 ± 13.2 | 34.2 ± 11.9 | 0.680 |
| Donor BMI (kg/m2) | 27.5 ± 6.3 | 27.1 ± 3.2 | 0.810 |
Data are shown as n (%), means ± standard deviation, or median (25th and 75th percentiles).
Abbreviations: BMI, body mass index; HAT, hepatic artery thrombosis; MELD, model for end-stage liver disease; PNF, primary non-function.
The etiologies of liver diseases leading to the initial transplantation were comparable between the two groups, with cholestatic diseases, non-alcoholic steatohepatitis, and viral hepatitis being the most common. The reason for the retransplant did differ between the two groups (P = 0.01). Early retransplant due to hepatic artery thrombosis or primary non-function accounted for 14 (23%) and 7 (12%) of the deceased donor transplants, respectively. Only one living donor retransplant was performed for hepatic artery thrombosis, and this was a late (>3 months after transplant) thrombosis. Overall, the most common reason for a retransplant was a recurrent disease, accounting for 40% of deceased donor transplants and 65% of living donor transplants. The median intervals from the initial transplant to the retransplant were 25.2 and 153.4 months in the deceased and living donor groups, respectively (P = 0.005). Early retransplants (within 3 months of the initial transplant) accounted for 35% of the deceased donor transplants but 0 of the living donor transplants (P < 0.01).
3.2. Operative course
The mean operative time was shorter in the deceased donor group than in the living donor group (516.8 ± 211.1 min vs. 657.6 ± 137.7 min, P = 0.03). Intraoperative transfusion of blood and blood products is shown in Table 2; overall, the living donor group required less blood transfusion than the deceased donor group (5.1 ± 3.0 vs. 10.0 ± 6.2, P = 0.02).
Table 2.
Outcomes of the deceased and living donor groups (N = 77).
| Characteristic | Deceased donor group (n = 60) | Living donor group (n = 17) | P-value |
|---|---|---|---|
| Operative time (min) | 516.8 ± 211.1 | 657.6 ± 137.7 | 0.03 |
| Number of units of blood transfused | 10.0 ± 6.2 | 5.1 ± 3.0 | 0.02 |
| Length of ICU stay (days) | 13.0 (3.0–32.0) | 7.0 (2.0–28.0) | 0.81 |
| Length of hospital stay (days) | 22.0 (11.0–44.0) | 14.0 (7.0–38.0) | 0.55 |
| Need for RRT, n (%) | 23 (38) | 1 (6) | 0.01 |
| Early reoperation (within 3 months of transplant), n (%) | 24 (40) | 4 (24) | 0.33 |
| HAT, n (%) | 2 (3) | 0 | 0.65 |
| Biliary complication, n (%) | 12 (20) | 4 (24) | 0.33 |
| Biliary leak | 3 (5) | 1 (6) | 0.81 |
| Bilary stenosis | 9 (15) | 3 (18) | 0.65 |
Data are shown as n (%), means ± standard deviation, or median (25th and 75th percentiles).
Abbreviations: HAT, hepatic artery thrombosis; ICU, intensive care unit; RRT, renal replacement therapy.
3.3. Postoperative course and complications
The median lengths of stay in the ICU were 13.0 and 7.0 days for the deceased and living donor groups, respectively (P = 0.81). The total length of hospital stay was also not significantly different between the two groups, with 22.0 and 14.0 days for the deceased and living donor groups, respectively.
Moreover, 38% (23/60) of patients in the deceased donor group and 6% (1/17) in the living donor group required renal replacement therapy (P = 0.01). In addition, 40% of patients in the deceased donor group and 24% in the living donor group required early reoperation (defined as within the first 3 months of transplant). The reasons for reoperation in the four living donor recipients included bleeding, intra-abdominal infection, outflow issues, and poor portal vein flow. Two cases of hepatic artery thrombosis were recorded in the deceased donor group but none in the living donor group. The rates of biliary complications overall (leaks and stenosis) were 20% and 24% in the deceased and living donor groups (P = 0.33).
3.4. Patient and graft survival
The survival curves for the two groups are shown in Fig. 1, and these were not statistically different. Patient survival rates at 1 and 3 years after transplant were 73% and 67% in the deceased donor group and 84% and 73% in the living donor group, respectively (P = 0.57). Of the 17 patients in the living donor group, 3 and 1 died from pulmonary hypertension and heart failure 7 days after transplant, respectively; 1 from aspergillus infection 14 days after transplant, and 1 from pneumonia and sepsis 10 months after transplant.
Fig. 1.
Patient and graft survival after retransplant in the living and deceased donor groups.
4. Discussion
The overall incidence of retransplants decreased because of improvements in immunosuppression, preservation modalities, and surgical/interventional techniques; however, retransplants still constitute 5%–10% of all transplants. They are likely at the lower range in Eastern countries, which are more reliant on living donor transplants, and at the upper range in Western countries, which are mostly based on deceased donors. Most Western centers do not offer living donor transplants for retransplant candidates, as they are considered to be too high risk. However, our data demonstrate that retransplants can be performed with acceptable results, which are comparable or better to the results obtained with deceased donors. Patient and graft survival, as well as surgical complications, were comparable between the two groups. Blood product use and dialysis use were both better in the living donor group. While our series represents the largest series of retransplants with living donors reported from an American program, many other programs including from the Middle East, India, and the Far East have reported good outcomes with retransplants using living donors.19, 20, 21, 22 A factor that distinguishes our series from these is the comparison in outcomes between deceased donors and living donors. Many Eastern centers do not offer options for deceased donors, with living donors as the only option.
Living donors offer several advantages over deceased donors for these transplants. The most notable is the ability to potentially avoid waitlist mortality and transplant patients earlier in their disease course before they become critically ill. This was reflected in our patient population, i.e., approximately 15% of the patients awaiting a deceased donor transplant died on the waitlist, whereas no deaths occurred in the living donor group. In addition, the MELD score was significantly lower in the living donor group than in the deceased donor group. This simply represents the harsh reality of deceased donor transplants in the USA today, as most recipients must have a high MELD score to be at the top of the waiting list. Another important advantage is the ability to get better at the time of the living donor transplant, which is essentially an elective procedure and can be done when the recipient's condition is optimized and the most experienced anesthesia and surgical teams are available for these complicated cases.
Complication rates were high after retransplants but were not significantly different between the living and deceased donor groups. In fact, several outcomes suggested a smoother course in the living donor group including less need for blood and blood products, less likelihood of needing posttransplant dialysis support, and shorter overall length of hospital stay. Infections were common in this group and highlighted the need for diligent postoperative care.
The technically complex nature of these transplants demands a systematic approach to these patients throughout their course to ensure acceptable outcomes. This begins well before the transplant procedure by appropriate selection of recipients and transplant timing. These procedures should be performed as soon as it is obvious that the patient will need a retransplant, but before significant debilitation, frailty, chronic infections, or multi-organ dysfunction have set in. This is applicable regardless of the donor source, i.e., living or deceased donors. The living donor should be chosen to provide a good-size graft (we exclusively use right lobe grafts for these patients) and not have overly complicated anatomy. If a suitable living donor is available and the recipient is acceptable for a retransplant, we do not exclude living donor liver transplantation based on the MELD score.
Before the transplant, the surgical team must review the details of the previous operative procedure and the recent imaging. This will ensure a good surgical plan for reconstruction and the ability to make sure vascular conduits are available if they may be needed. During the transplant, helpful technical details include careful dissection, staying close to the liver, getting retractors in early, and doing the portal dissection first before extensive liver mobilization. Finally, after transplant, these patients must be followed extremely closely to identify problems as early as possible and address them appropriately.
While this study is limited by its retrospective nature and small sample, the clinical situation and problems with donor availability make a randomized study very difficult. An advantage of our analysis is related to the comparison of outcomes between living and deceased donors in a single center, where protocols and clinical teams are consistent.
5. Conclusion
In this study, no significant difference was found in outcomes associated with liver retransplants using living or deceased donors. A living donor transplant offers many advantages for these patients and should always be considered a possible option.
Authors’ contributions
Hasan Al Harakeh, Christopher Hughes, Amit Tevar, Vikram Gunabushanam, and Abhinav Humar contributed to the conception/design, data-analysis/interpretation, drafting and critical revision of the article. Eishan Ashwat and Hao Liu were involved in data collection and analysis. Hasan Al Harakeh and Abhinav Humar conceived and designed the project, supervised reviewing the records, prepared, revised and reviewed the manuscript draft. All authors have read and approved the final manuscript.
Declaration of competing interest
The authors declare that they have no conflicts of interest.
Footnotes
Edited by Yuxia Jiang and Peiling Zhu.
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