Safety and feasibility of chemotherapy followed by liver transplantation for patients with definitely unresectable colorectal liver metastases: insights from the TransMet randomised clinical trial.

Background: Despite the increasing efficacy of chemotherapy (C), the 5-year survival rate for patients with unresectable colorectal liver metastases (CLM) remains around 10%. Liver transplantation (LT) might offer a curative approach for patients with liver-only disease, yet its superior efficacy compared to C alone remains to be demonstrated. Methods: The TransMet randomised multicentre clinical trial (NCT02597348) compares the curative potential of C followed by LT versus C alone in patients with unresectable CLM despite stable or responding disease on C. Patient eligibility criteria proposed by local tumour boards had to be validated by an independent committee via monthly videoconferences. Outcomes reported here are from a non-specified interim analysis. These include the eligibility of patients to be transplanted for non resectable colorectal liver metastases, as well as the feasibility and the safety of liver transplantation in this indication. Findings: From February 2016 to July 2021, 94 (60%) of 157 patients from 20 centres in 3 countries submitted to the validation committee, were randomised. Reasons for ineligibility were mainly tumour progression in 50 (32%) or potential resectability in 13 (8%). The median delay to LT after randomisation was 51 (IQR 30-65) days. Nine of 47 patients (19%, 95% CI: 9-33) allocated to the LT arm failed to undergo transplantation because of intercurrent disease progression. Three of the 38 transplanted patients (8%) were re-transplanted, one of whom (3%) died post-operatively from multi-organ failure. Interpretation: The selection process of potential candidates for curative intent LT for unresectable CLM in the TransMet trial highlighted the critical role of an independent multidisciplinary validation committee. After stringent selection, the feasibility of LT was 81%, as 19% had disease progression while on the waiting list. These patients should be given high priority for organ allocation to avoid dropout from the transplant strategy. Funding: No source of support or funding from any author to disclose for this work. The trial was supported by the Assistance Publique - Hôpitaux de Paris (AP-HP).

COVID-free surgical pathways for treating patients with acute calculous cholecystitis: a retrospective comparative study.

Introduction: During the Sars-Cov-2 crisis, some of the resources committed to emergency surgery services were transiently reallocated to the care of patients with severe COVID-19, preserving immediate treatment of mostly non-deferrable conditions. Moreover, the fear of contracting infections or hindering the treatment of critical COVID-19 patients has caused many individuals to defer seeking emergency care. This situation has then possibly modified the standard of care of some common surgical conditions and the relative outcomes. Our aims was to highlight any difference in surgical outcomes in patients treated for acute cholecystitis before and during the COVID-19 outbreak. Method: This is a retrospective study on a prospectively collected database that included all consecutive patients treated for acute cholecystitis from March 2019 to February 2021 at the Lugano Regional Hospital, a COVID-free hospital for general surgery patients. Patients were divided into pre-and post-COVID-19 outbreak groups. We collected thorough clinical characteristics and intra-and postoperative outcomes. Results: We included 124 patients, of which 60 and 64 were operated on before and after the COVID-19 outbreak respectively. The two groups resulted similar in terms of patients' clinical characteristics (age, gender, body mass index, ASA score, and comorbidities). Patients in the post-outbreak period were admitted to the hospital 0.7 days later than patients in the pre-outbreak period (3.8 ± 6.0 days vs. 3.1 ± 4.1 days, p = 0.453). Operative time, recovery room time, complications, and reoperations resulted similar between groups. More patients in the post-outbreak period received postoperative antibiotic therapy (63.3% vs. 37.5%, p = 0.004) and for a longer time (6.9 ± 5.1 days vs. 4.5 ± 3.9 days, p = 0.020). No significant histopathological difference was found in operatory specimens. Discussion: Despite more frequent antibiotic therapy that suggests eventually worse inflammatory local status, our results showed similar outcomes for patients treated for acute cholecystitis before and during the COVID-19 pandemic. The local COVID management, reallocating resources, and keeping COVID-free hospitals was key to offering patients a high standard of treatment.

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells.

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.

Liver Transplantation Selection and Allocation Criteria for Hepatocellular Carcinoma: A European Perspective.

For patients with early-stage hepatocellular carcinoma (HCC), liver transplantation offers the best chance of cure. Over the past two decades, selection criteria to determine eligibility for liver transplantation have been constantly refined but a fair allocation strategy of liver grafts to HCC patients remains challenging. In Europe, over a dozen transplantation networks apply different liver transplantation criteria for HCC patients. In this review, we explore and compare candidate selection and liver graft allocation strategies for patients with HCC with a European perspective and discuss the ethical and technical challenges involved. In addition, we suggest possible paths for future improvement such as transitioning from fixed selection and allocation criteria to a more flexible model of benefit, which includes criteria concerning the graft, response to treatment, the biology of the tumor, and other relevant recipient factors.

Stratification of Major Hepatectomies According to Their Outcome: Analysis of 2212 Consecutive Open Resections in Patients Without Cirrhosis.

OBJECTIVE: To stratify major hepatectomies (MajHs) according to their outcomes. SUMMARY OF BACKGROUND DATA: MajHs are associated with non-negligible operative risks, but they include a wide range of procedures. Detailed depiction of the outcomes of different MajHs is the basis for a new classification of liver resections. METHODS: We retrospectively considered patients that underwent hepatectomy in 17 high-volume centers. Patients with an associated digestive/biliary resection were excluded. We analyzed open MajHs in non-cirrhotic patients. MajHs were classified according to the Brisbane nomenclature. Right hepatectomies (RHs) were reference standards. Outcomes were adjusted for potential confounders, including indication, liver function, preoperative portal vein embolization, and enrolling center. RESULTS: We analyzed a series of 2212 patients. In comparison with RH, left hepatectomy had lower mortality [0.6% vs 2.2%, odds ratio (OR) = 0.25], severe morbidity (11.7% vs 14.4%, OR = 0.62), and liver failure rates (2.1% vs 11.6%, OR = 0.16). Left hepatectomy+Sg1 and mesohepatectomy+/-Sg1 had outcomes similar to RH, except for higher bile leak rate (31.3% and 13.5% vs 6.7%, OR = 4.36 and OR = 2.29). RH + Sg1 had slightly worse outcomes than RH. Right and left trisectionectomies had higher mortality (5.0% and 7.3% vs 2.2%, OR = 2.07 and OR = 2.71) and liver failure rates than RH (19.0% and 22.0% vs 11.6%, OR = 2.03 and OR = 2.21). Left trisectionectomy had even higher severe morbidity (25.6% vs 14.4%, OR = 2.07) and bile leak rates (14.6% vs 6.7%, OR = 2.31). CONCLUSIONS: The term "major hepatectomy" includes resections having heterogeneous outcome. Different MajHs can be stratified according to their mortality, severe morbidity, liver failure, and bile leak rates.

Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer.

Immune cell infiltration in colorectal cancer effectively predicts clinical outcome. IL22, produced by immune cells, plays an important role in inflammatory bowel disease, but its relevance in colorectal cancer remains unclear. Here, we addressed the prognostic significance of IL22+ cell infiltration in colorectal cancer and its effects on the composition of tumor microenvironment. Tissue microarrays (TMA) were stained with an IL22-specific mAb, and positive immune cells were counted by expert pathologists. Results were correlated with clinicopathologic data and overall survival (OS). Phenotypes of IL22-producing cells were assessed by flow cytometry on cell suspensions from digested specimens. Chemokine production was evaluated in vitro upon colorectal cancer cell exposure to IL22, and culture supernatants were used to assess neutrophil migration in vitro Evaluation of a testing (n = 425) and a validation TMA (n = 89) revealed that high numbers of IL22 tumor-infiltrating immune cells were associated with improved OS in colorectal cancer. Ex vivo analysis indicated that IL22 was produced by CD4+ and CD8+ polyfunctional T cells, which also produced IL17 and IFNγ. Exposure of colorectal cancer cells to IL22 promoted the release of the neutrophil-recruiting chemokines CXCL1, CXCL2, and CXCL3 and enhanced neutrophil migration in vitro Combined survival analysis revealed that the favorable prognostic significance of IL22 in colorectal cancer relied on the presence of neutrophils and was enhanced by T-cell infiltration. Altogether, colorectal cancer-infiltrating IL22-producing T cells promoted a favorable clinical outcome by recruiting beneficial neutrophils capable of enhancing T-cell responses.

Liver transplantation for hepatocellular carcinoma after successful treatment of macrovascular invasion - a multi-center retrospective cohort study.

Macrovascular invasion is considered a contraindication to liver transplantation for hepatocellular carcinoma (HCC) due to a high risk of recurrence. The aim of the present multicenter study was to explore the outcome of HCC patients transplanted after a complete radiological regression of the vascular invasion by locoregional therapies and define sub-groups with better outcomes. Medical records of 45 patients were retrospectively reviewed, and imaging was centrally assessed by an expert liver radiologist. In the 30 patients with validated diagnosis of macrovascular invasion, overall survival was 60% at 5 years. Pretransplant alpha-fetoprotein (AFP) value was significantly different between patients with and without recurrence (P = 0.019), and the optimal AFP cutoff was 10ng/ml (area under curve = 0.78). Recurrence rate was 11% in patients with pretransplant AFP < 10ng/ml. The number of viable nodules (P = 0.008), the presence of residual HCC (P = 0.036), and satellite nodules (P = 0.001) on the explant were also significantly different between patients with and without recurrence. Selected HCC patients with radiological signs of vascular invasion could be considered for transplantation, provided that they previously underwent successful treatment of the macrovascular invasion resulting in a pretransplant AFP < 10 ng/ml. Their expected risk of post-transplant HCC recurrence is 11%, and further prospective validation is needed.

Safety of variceal band ligation in patients with cirrhosis and portal vein thrombosis treated with anticoagulant therapy: A retrospective study.

BACKGROUND AND AIMS: Anticoagulant therapy has been recommended in patients with cirrhosis and portal vein thrombosis especially in candidates for liver transplantation. These patients are also likely to need variceal band ligation. This study aimed to assess the incidence of upper gastrointestinal bleeding after elective variceal band ligation in patients with cirrhosis receiving anticoagulant therapy for portal vein thrombosis. METHODS: Patients with cirrhosis and nontumoral portal vein thrombosis treated with anticoagulant therapy undergoing elective variceal band ligation were retrospectively included. We recorded upper gastrointestinal bleeding events occurring within two weeks after variceal band ligation. Postvariceal band ligation bleeding was defined as active bleeding on at least one site of previous ligation at endoscopy. RESULTS: Between 2014 and 2017, 32 patients with cirrhosis had scheduled variceal band ligations while on anticoagulant therapy [men 75%; median age 59 years; aetiology of cirrhosis: alcohol (50%), viral (34%), alcohol and viral (16%); and Child-Pugh score: A (31%), B (44%), and C (25%)]. Three (9%) patients presented postvariceal band ligation bleeding during the follow-up. None of these events led to haemorrhagic shock or death. Factors associated with postvariceal band ligation bleeding included variceal band ligation performed as secondary prophylaxis (P = 0.05) and previous decompensation of cirrhosis (P = 0.03). CONCLUSION: In this small group of patients under anticoagulation therapy undergoing variceal band ligation, only a minority presented postendoscopic bleeding of minor importance. Nevertheless, particular attention should be paid to patients with previous decompensation of cirrhosis.

Minor Hepatectomies: Focusing a Blurred Picture: Analysis of the Outcome of 4471 Open Resections in Patients Without Cirrhosis.

OBJECTIVE: To elucidate minor hepatectomy (MiH) outcomes. SUMMARY BACKGROUND DATA: Liver surgery has moved toward a parenchyma-sparing approach, favoring MiHs over major resections. MiHs encompass a wide range of procedures. METHODS: We retrospectively evaluated consecutive patients who underwent open liver resections in 17 high-volume centers. EXCLUSION CRITERIA: cirrhosis and associated digestive/biliary resections. Resections were classified as (Brisbane nomenclature): limited resections (LR); (mono)segmentectomies/bisegmentectomies (Segm/Bisegm); right anterior and right posterior sectionectomies (RightAnteriorSect/RightPosteriorSect). Additionally, we defined: complex LRs (ComplexLR = LRs with exposed vessels); postero-superior segmentectomies (PosteroSuperiorSegm = segment (Sg)7, Sg8, and Sg7+Sg8 segmentectomies); and complex core hepatectomies (ComplexCoreHeps = Sg1 segmentectomies and combined resections of Sg4s+Sg8+Sg1). Left lateral sectionectomies (LLSs, n = 442) and right hepatectomies (RHs, n = 1042) were reference standards. Outcomes were adjusted for potential confounders. RESULTS: Four thousand four hundred seventy-one MiHs were analyzed. Compared with RHs, MiHs had lower 90-day mortality (0.5%/2.2%), severe morbidity (8.6%/14.4%), and liver failure rates (2.4%/11.6%, P < 0.001), but similar bile leak rates. LR and LLS had similar outcomes. ComplexLR and Segm/Bisegm of anterolateral segments had higher bile leak rates than LLS rates (OR = 2.35 and OR = 3.24), but similar severe morbidity rates. ComplexCoreHeps had higher bile leak rates than RH rates (OR = 1.94); the severe morbidity rate approached that of RH. PosteroSuperiorSegm, RightAnteriorSect, and RightPosteriorSect had severe morbidity and bile leak rates similar to RH rates. MiHs had low liver failure rates, except RightAnteriorSect (vs LLS OR = 4.02). CONCLUSIONS: MiHs had heterogeneous outcomes. Mortality was low, but MiHs could be stratified according to severe morbidity, bile leak, and liver failure rates. Some MiHs had postoperative outcomes similar to RH.

ERAS, length of stay and private insurance: a retrospective study.

PURPOSE: Hospital discharge after colorectal resection within an Enhanced Recovery After Surgery (ERAS) program occurs earlier compared to standard-care postoperative pathways but often later than what objective criteria of "readiness for discharge" could allow. The aim of this study was to analyse reasons and risk factors of such discharge delay. METHODS: All elective patients admitted for colorectal resection at the regional Hospital of Lugano in 2014 and 2015 were included. The postoperative day on which patients fulfilled consensus agreed criteria (according to Fiore) for readiness for discharge (POD-F) and the effective day of discharge (POD-D) were determined. We analysed the reasons for discharge delay (POD-D>POD-F) and performed univariate and multivariate analysis to determine risk factors. RESULTS: One hundred thirty-eight patients were included in the study. Median POD-F was 5 (2-48) days, POD-D was 6 (3-50) days. In 94 patients, POD-D occurred later than POD-F with a median delay of 1 (1-11) days. Reasons for discharge delay were insufficient social support in 13 (14%), patient's preference in 39 (41%) and medical team preference in 41 (44%). Private insurance (OR 2.61, 95%CI 1.08-6.34, p = 0.034) and patient discharged on a day other than Monday (OR 2.94, 95%CI 1.16-7.14, p = 0.023) were independent predictors for discharge delay. CONCLUSION: Even when objective criteria for readiness for discharge have been fulfilled, patients and/or doctors often do not feel comfortable with hospital discharge at this time point. Length of stay, even within an ERAS program, is still influenced by several non-medical factors and is therefore not a precise surrogate marker of outcomes.

Downstaging prior to liver transplantation for hepatocellular carcinoma: advisable but at the price of an increased risk of cancer recurrence - a retrospective study.

The use of downstaging prior to liver transplantation for hepatocellular carcinoma (HCC) still needs refinement. This study included patients with HCC listed for transplantation according to the Total Tumour Volume (TTV) ≤115 cm3 and alpha fetoprotein (AFP) ≤400 ng/ml criteria, with and without previous downstaging. Overall, 455 patients were listed, and 286 transplanted. Post-transplant follow-up was 38.5 ± 1.7 months. Patients downstaged to TTV115/AFP400 (n = 29) demonstrated similar disease-free survivals (DFS, 74% vs. 80% at 5 years, P = 0.949), but a trend to more recurrences (14% vs. 5.8%, P = 0.10) than those always within TTV115/AFP400 (n = 257). Similarly, patients downstaged to Milan criteria (n = 80) demonstrated similar DFS (76% vs. 86% at 5 years, P = 0.258), but more recurrences (11% vs. 1.7%, P = 0.001) than those always within Milan (n = 177). Among patients downstaged to Milan, those originally beyond TTV115/AFP400 (n = 27) had similar outcomes as those originally beyond Milan, but within TTV115/AFP400 (n = 53). However, the likelihood of being within Milan at transplant was lower for patients with more advanced original HCCs (P < 0.0001). Overall, despite an expected increase in post-transplant HCC recurrence, similar survivals can be achieved with and without downstaging, using the TTV115/AFP400 transplantation criteria, and including patients with advanced original HCCs. Downstaging should continue to be performed.

Left-liver Adult-to-Adult Living Donor Liver Transplantation: Can It Be Improved? A Retrospective Multicenter European Study.

OBJECTIVE: To evaluate the European experience after Adult-to-adult living donor liver transplantation using the left liver (LL-aLDLT). SUMMARY BACKGROUND DATA: LL-aLDLT decreases donor risk but provides a smaller graft that increases recipient risk as compared with right liver (RL-aLDLT). However, there is little knowledge of results obtained after LL-aLDLT in Europe. METHODS: This is a European multicenter retrospective study which aims to analyze donor and recipient outcomes after 46 LL-aLDLT. RESULTS: Seventy-six percent of the grafts were harvested by minimally invasive approach. Mean donor hospital stay was 7.5 ±â€Š3.5 days. Donor liver function was minimally impaired, with 36 donors (78.3%) without any 90-day complication, and 4 (8.7%) presenting major complications. One, 3, and 5-year recipient survival was 90.9%, 82.7%, and 82.7%, respectively. However, graft survival was of 59.4%, 56.9%, and 56.9% at 1, 3, and 5 years respectively, due to a 26.1% urgent liver retransplantation (ReLT) rate, mainly due to SFSS (n = 5) and hepatic artery thrombosis (HAT, n = 5). Risk factor analysis for ReLT and HAT showed an association with a graft to body weight ratio (GBWR) <0.6% (P = 0.01 and P = 0.024, respectively) while SFSS was associated with a recipient MELD ≥14 (P = 0.019). A combination of donor age <45 years, MELD <14 and actual GBWR >0.6% was associated with a lower ReLT rate (0% vs. 33%, P = 0.044). CONCLUSIONS: Our analysis showed low donor morbidity and preserved liver function. Recipient outcomes, however, were hampered by a high ReLT rate. A strict selection of both donor and recipients is the key to minimize graft loss.

Medullary-like hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent primary hepatic cancer. Pathological features can define the biological behavior and prognosis. Medullary-like HCC is a very rare variant that has been described only twice in literature. In the present study, we report the case of a non-cirrhotic 72-year-old man, who presented two HCC lesions on routine screening for hepatitis C virus liver disease. Radiological imaging and biopsy showed two different subtypes: one classic HCC, which was treated with chemoembolization, and a second PET/CT-positive carcinoma with a PET/CT-positive metastatic coeliac lymph node, which was resected laparoscopically with a left lateral sectionectomy and extended lymphadenectomy. Histopathology revealed a medullary-like HCC; lymph node analysis confirmed the metastatic nature of the PET/CT-positive coeliac node and showed an incidental B-cell lymphoma in the hepatic pedicle lymph nodes. To the best of our knowledge this is the third case of medullary-like HCC described in the literature, and the first associated to a concomitant typical HCC.

In situ liver splitting under extracorporeal membrane oxygenation in brain-dead donor.

Hemodynamic instability is generally considered as a contraindication to liver splitting, in particular when using an in situ technique. We describe the cases of two young donors with brain death in whom refractory cardiac arrest and hemodynamic instability were supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO), allowing uneventful in situ splitting. Two adult and two pediatric liver recipients were successfully transplanted with immediate graft function. Favorable outcomes were also observed for the other transplanted organs, including one heart, two lungs, and four kidneys. Refractory cardiac arrest and hemodynamic instability corrected by VA-ECMO should not be considered as a contraindication to in situ liver splitting.

mTOR Inhibition and Clinical Transplantation: Pancreas and Islet.

This brief overview discusses the beneficial and deleterious effects of mammalian target of rapamycin (mTOR) inhibitors on ß cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from greater than 80% to less than 50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to less than 10% currently. This decrease is arguably due to less well-tolerated side effects without the advantage of better outcomes. Nonetheless, mTOR inhibitors remain extremely valuable as second-line immunosuppressants in pancreas and islet transplantation.

Reversibility of chemotherapy-related liver injury.

BACKGROUND & AIMS: Chemotherapy-associated liver injury (CALI) increases the risk of liver resection and may prejudice further surgery and chemotherapy. The reversibility of CALI is therefore important; however, no data concerning this are available. This study aimed to retrospectively analyze the reversibility of CALI in patients undergoing liver resection for colorectal metastases. METHODS: All resections of colorectal liver metastases after oxaliplatin and/or irinotecan-based chemotherapy were included. First, liver resections were stratified by time between end of chemotherapy and hepatectomy and several possible cut-off values tested. CALI prevalence in various groups was compared. Second, CALI in the two specimens from each patient who had undergone repeat liver resections without interval chemotherapy were compared. RESULTS: Overall, 524 liver resections in 429 patients were analyzed. The median interval chemotherapy-surgery was 56days (15-1264). CALI prevalence did not differ significantly between groups with a chemotherapy-surgery interval <270days. Grade 2-3 sinusoidal dilatation (SOS, 19.4% vs. 40.0%, p=0.022) and nodular regenerative hyperplasia (NRH, 6.5% vs. 20.1%, p=0.063) occurred less frequently in patients with an interval >270days (n=31); prevalence of steatosis and steatohepatitis was similar in all groups. A chemotherapy-surgery interval >270days was an independent protector against Grade 2-3 SOS (p=0.009). Forty-seven patients had repeat liver resection without interval chemotherapy. CALI differed between surgeries only for a chemotherapy-surgery interval >270days (n=15), Grade 2-3 SOS having regressed in 4/5 patients and NRH in 7/8; whereas steatosis and steatohepatitis had persisted. CONCLUSIONS: CALI persists for a long time after chemotherapy. SOS and NRH regress only after nine months without chemotherapy, whereas steatosis and steatohepatitis persist. LAY SUMMARY: The patients affected by colorectal liver metastases often receive chemotherapy before liver resection, but chemotherapy causes liver injuries that may increase operative risks and reduce tolerance to further chemotherapy. The authors analyzed the reversibility of the liver injuries after the chemotherapy interruption. Liver injuries persist for a long time after chemotherapy. Sinusoidal dilatation and nodular regenerative hyperplasia regress only nine months after the end of chemotherapy, whereas steatosis and steatohepatitis persist even after this long interval.

Early complications after liver transplantation in children and adults: Are split grafts equal to each other and equal to whole livers?

Split-liver transplantation (LT) allows transplantation of two recipients from one deceased donor, thereby increasing pool of grafts. However, split LT may be hampered by technical problems, and split grafts are still considered suboptimal organs in some centres. We analysed the outcomes in split- and whole-liver recipients in a combined adult-to-paediatric transplantation programme. Records of paediatric and adult patients having undergone LT from 1999 to 2013 were analysed retrospectively. All splits were performed in situ. Adult split-graft recipients were matched 1:2 with whole-graft recipients (matching criteria: BMI, MELD, year of transplantation, age), and matched to the paediatric recipient transplanted from the same donor. Post-LT complications were classified according to the Clavien scale. Among children, 32 split- and 31 whole-graft recipients were analysed. Among adults, 20 split- and 40 matched whole-graft recipients were analysed. In both populations, the post-operative complications did not differ between split- and whole-graft recipients. There was no difference in 1-year graft and patient survival between split- and whole-graft recipients in paediatric (90% vs. 97%, 94% vs. 97%, respectively) and in adult recipients (89% in both, 89% vs. 92%, respectively). In the analysis of both recipients issued from the same donor, there was no association in the prevalence and severity of complications. A case-by-case analysis showed that split mortality was unrelated to LT in all but one patient (small-for-size left split graft). In the setting of careful donor selection, recipient matching and surgical skill, in situ split LT is an effective and safe technique to increase the number of available organs, and split livers should no longer considered marginal grafts.