The technique of abdominal organ procurement in cDCD donors in Italy has been previously described in detail [17], and the timeline of events is reported in Supplementary Figure S1.

After circulatory arrest and no-touch time, NRP is initiated, targeting lactate clearance, pH normalization, normocapnia, and avoidance of hyperoxemia; hemoglobin concentration is maintained above 8 g/dL and hyperglicemia is corrected to facilitate organ resuscitation. Since NRP starts every 30′, blood gas analysis and liver enzyme measurement are performed throughout extracorporeal perfusion. NRP is maintained for at least 60–90 min to assess the organ functional recovery; the criteria of viability include fWIT<60 min, pH normalization and stability, progressive lactate decrease, and SGOT/SGPT decrease (usually evident after 30 min of NRP). When the metabolic and perfusion profiles of the donors are considered optimal, the surgical procedure is initiated: first, liver (and kidney) biopsies are obtained, then the warm dissection phase of the procurement is performed. In our practice, liver biopsy is a cornerstone to assess organ viability, as the presence of extensive lobular necrosis represents a contraindication to further proceed with retrieval.

NRP ends with in-situ cold preservation (ISP): once the organs are retrieved, they are put in static cold storage (SCS) to be transported to the transplant center where bench surgery is performed, and HOPE is implemented until implantation.

Conversely, liver grafts from DBD donors were retrieved with standard technique and preserved with SCS until implantation.

For DCD donors, total WIT (tWIT) was defined as the timeframe occurring between WLST and NRP initiation, while functional WIT (fWIT) was defined as the timeframe between hypotension (systolic arterial pressure below 50 mmHg) or desaturation (peripheral oxygen saturation below 70%)—whichever occurring first—and NRP initiation. Cold preservation time (CPT) was defined as the interval from aortic cross-clamping/ISP and portal reperfusion upon LT, thus including both SCS and HOPE duration (Figure 1).

Complications were defined as any event deviating from the expected postoperative course that does not imply failure to cure [18]. For each patient, the postoperative complications were graded according to the Clavien-Dindo classification [18] and summarized through the Comprehensive Complication Index (CCI®) [19]; major complications were defined as Clavien-Dindo grade ≥3A.

Post-reperfusion syndrome (PRS) was defined according to Aggarwal et al. [20] Primary non-function (PNF) of the graft was defined according to the Organ Procurement and Transplantation Network (OPTN) criteria [21], while early allograft dysfunction (EAD) was defined according to the criteria proposed by Olthoff et al. [22] Severe acute kidney injury was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline [23].

Qualitative variables were reported as absolute values and percentages, whereas quantitative variables were reported as median values and IQR or mean ± SD as appropriate. Univariate analysis was performed using Pearson’s chi-squared or Fisher’s exact test for categorical variables, depending on the sample size, and with Student’s t-test or Mann-Whitney U test for continuous variables, depending on their distribution.

PSM was performed through logistic regression analysis to adjust for clinically confounding factors between groups, including donor age, recipient age at the time of transplantation, MELD score, and hepatocellular carcinoma (HCC) as an indication for LT. DCD and DBD recipients were matched in a 1:3 ratio with the closest estimated propensity. Survival curves were plotted with the Kaplan-Meier estimators and compared through the log-rank test.

Differences of p < 0.05 were considered significant.

All the statistical analyses were performed using IBM SPSS, version 26.0 (IBM Corporation—Armonk, NY).

Compared with DBD donors, DCDs had higher median age (75 years vs. 63 years, p = 0.018); notably, most DCD donors were 75 years or older. Recipients of DCD liver grafts had lower MELD scores (10 vs. 15, p < 0.001), and were more often transplanted due to HCC (69.2% vs. 41.2%, p = 0.009). Full demographic and clinical characteristics of recipients and donors are summarized in Table 1.

After PSM, the population resulted in 26 DCD donors and 78 DBD donors; the subsequent analysis demonstrated the comparability of baseline characteristics (Table 1).

DCD grafts had a median tWIT of 45 min and a median fWIT of 40 min, with a median timeframe of 6 min from death declaration to NRP initiation. NRP had a median duration of 209 min and end-ischemic HOPE had a median duration of 105 min. No significant differences have been observed between elder and younger DCD donors in terms of tWIT, fWIT, NRP duration, metabolic and functional parameters during NRP (pH, lactates, SGOT, SGPT), bioptic findings, or HOPE duration. These results are summarized in Supplementary Table S1. Grafts from DCD donors underwent shorter CPT (345 vs. 388 min, p = 0.010) and shorter duration of transplant (430 vs. 470 min, p = 0.040).

The analysis of postoperative data showed that recipients of livers from DCD and DBD donors had comparable results in terms of surgical complications, length of hospital stay, and graft function (Table 2).

After stratification by age, three subgroups were identified: 15 recipients of DCD donors ≥75 years, 11 recipients of DCD donors <75 years, and 28 recipients of DBD donors ≥75 years. No significant differences were evident in terms of CPT, surgical complications, length of hospital stay, and graft function. One recipient of an elder DCD donor experienced PNF and was successfully retransplanted. Amongst the elder DBD recipients two have been retransplanted due to PNF in one case and hepatic artery thrombosis in the other; another recipient of an elder DBD donor died a few hours after LT due to massive myocardial infarction. Altogether, six patients developed biliary complications during the follow-up period (with comparable rates between groups), all consisting of anastomotic strictures with successful endoscopic management. The results are summarized in Table 3. Patients were followed up for a median of 19 months [IQR: 14–24 months] without any significant difference in terms of graft survival for the three subgroups (Figure 1).

This study has some limitations. First, the need for case-matching, as well as the limited number of patients in the derived subgroups, affected our ability to draw definite conclusions. Nevertheless, the relatively limited size of the study group reflects a hopefully initial experience with very elderly DCD donors. The short duration of the study implied a limited follow-up for the patients with a late enrolment, although a minimum twelve-month follow-up was provided for all the included recipients. Finally, in this study, we compared grafts from elderly cDCD donors—exposed to extensive reconditioning through NRP and end-ischemic HOPE—with ECD liver grafts (at least according to donor age) from DBD donors, which have been implanted without advanced perfusion strategies. This approach might be considered a bias, as DBD grafts can benefit from HOPE too [35, 36], but it reflects the state of the art in DCD liver transplantation in Italy. In fact, under Italian legal and procedural circumstances, this approach enabled the safe transplant of organs potentially carrying a relevant ischemic burden. Moreover, its extensive use also achieved comparable outcomes between cDCD grafts and ECD grafts, with the latter still being transplanted without HOPE in the majority of transplant centers worldwide.

According to the preliminary results of our single center experience, the inclusion of very elderly cDCD donors in liver transplantation programs might provide acceptable outcomes, comparable to those achieved with younger cDCD donors, and with same-age DBD donors. With donor management and graft allocation and reconditioning becoming more and more accurate as further experience and evidence accumulate, the ability of clinicians to achieve optimal utilization and to improve transplantation outcomes for DCD grafts will be enhanced, overcoming existing concerns about these donors’ perceived marginality.