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Background: The challenge of transplant waiting-lists is to provide organs for all candidates while maintaining efficiency and equity., Aims: We investigated the probability of being transplanted or of waiting-list dropout in Italy., Methods: Data from 12,749 adult patients waitlisted for primary liver-transplantation from January 2012 to December 2022 were collected from the National Transplant-Registry.The cohort was divided into Eras:1 (2012-2014);2 (2015-2018);and 3 (2019-2022)., Results: The one-year probability of undergoing transplant increased (67.6 % in Era 1vs73.8 % in Era 3,p < 0001) with a complementary 46 % decrease in waiting-list failures. Patients with hepatocellular-carcinoma were transplanted more often than cirrhotics[at model for end-stage liver-disease (MELD)-15:HR = 1.28,95 %CI:1.21-1.35;at MELD-25:HR = 1.04,95 %CI:0.92-1.19) and those with other indications (at MELD-15:HR = 1.27,95 %CI:1.11-1.46) across all eras. Candidates with Hepatitis-B-virus (HBV)related disease had a greater probability of transplant than those with Hepatitis-C virus-related (HR = 1.13,95 %CI:1.07-1.20), alcohol-related (HR = 1.13,95 %CI:1.05-1.21), and metabolic-related (HR = 1.18,95 %CI:1.09-1.28)disease. Waiting-list failures increased by 27 % every 5 MELD-points and by 14 % for every 5-year increase in recipient-age and decreased by 10 % with each 10-cm increase in stature. Blood-group O patients showed the highest probability of waiting-list failure (HR = 1.28,95 %CI:1.15-1.43)., Conclusions: Liver-transplantation waiting-list success-rates have significantly improved in Italy, with patients with hepatocellular-carcinoma and/or HBV-related diseases being favored. High MELD-score, old-age, short-stature, and blood-group O were significant risk-factors for waiting-list failure. Efforts to improve organ-allocation and prioritization-policies are underway., Competing Interests: Conflict of interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Introduction: Three-dimensional liver modeling can lead to substantial changes in choosing the type and extension of liver resection. This study aimed to explore whether 3D reconstruction helps to better understand the relationship between liver tumors and neighboring vascular structures compared to standard 2D CT scan images., Methods: Contrast-enhanced CT scan images of 11 patients suffering from primary and secondary hepatic tumors were selected. Twenty-three experienced HBP surgeons participated to the survey. A standardized questionnaire outlining 16 different vascular structures (items) having a potential relationship with the tumor was provided. Intraoperative and histopathological findings were used as the reference standard. The proper hypothesis was that 3D accuracy is greater than 2D. As a secondary endpoint, inter-raters' agreement was explored., Results: The mean difference between 3D and 2D, was 2.6 points (SE: 0.40; 95 % CI: 1.7-3.5; p < 0.0001). After sensitivity analysis, the results favored 3D visualization as well (mean difference 1.7 points; SE: 0.32; 95 % CI: 1.0-2.5; p = 0.0004). The inter-raters' agreement was moderate for both methods (2D: W = 0.45; 3D: W = 0.44)., Conclusion: 3D reconstruction may give a significant contribution to better understanding liver vascular anatomy and the precise relationship between the tumor and the neighboring structures., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: Split liver transplant(ation) (SLT) is still considered a challenging procedure that is by no means widely accepted. We aimed to present data on 25-year trends in SLT in Italy, and to investigate if, and to what extent, outcomes have improved nationwide during this time., Methods: The study included all consecutive SLTs performed from May 1993 to December 2019, divided into three consecutive periods: 1993-2005, 2006-2014, and 2015-2019, which match changes in national allocation policies. Primary outcomes were patient and graft survival, and the relative impact of each study period., Results: SLT accounted for 8.9% of all liver transplants performed in Italy. A total of 1,715 in situ split liver grafts were included in the analysis: 868 left lateral segments (LLSs) and 847 extended right grafts (ERGs). A significant improvement in patient and graft survival (p <0.001) was observed with ERGs over the three periods. Predictors of graft survival were cold ischaemia time (CIT) <6 h (p = 0.009), UNOS status 2b (p <0.001), UNOS status 3 (p = 0.009), and transplant centre volumes: 25-50 cases vs. <25 cases (p = 0.003). Patient survival was significantly higher with LLS grafts in period 2 vs. period 1 (p = 0.008). No significant improvement in graft survival was seen over the three periods, where predictors of graft survival were CIT <6 h (p = 0.007), CIT <6 h vs. ≥10 h (p = 0.019), UNOS status 2b (p = 0.038), and UNOS status 3 (p = 0.009). Retransplantation was a risk factor in split liver graft recipients, with significantly worse graft and patient survival for both types of graft (p <0.001)., Conclusions: Our analysis showed Italian SLT outcomes to have improved over the last 25 years. These results could help to dispel reservations regarding the use of this procedure., Impact and Implications: Split liver transplant(ation) (SLT) is still considered a challenging procedure and is by no means widely accepted. This study included all consecutive in situ SLTs performed in Italy from May 1993 to December 2019. With more than 1,700 cases, it is one of the largest series, examining long-term national trends in in situ SLT since its introduction. The data presented indicate that the outcomes of SLT improved during this 25-year period. Improvements are probably due to better recipient selection, refinements in surgical technique, conservative graft-to-recipient matching, and the continuous, yet carefully managed, expansion of donor selection criteria under a strict mandatory split liver allocation policy. These results could help to dispel reservations regarding the use of this procedure., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the influence of postoperative complications on tumor-related (TRD), disease-free survival (DFS) and overall survival (OS) in patients undergoing liver transplant (LT) for hepatocellular carcinoma (HCC)., Methods: We retrospectively evaluated 425 LTs for HCC from 2010 to 2019. Postoperative complications were classified according to Comprehensive Complication Index (CCI) and the posttransplant risk of TRD assessed through Metroticket 2.0 calculator. The population was stratified into high-risk and low-risk cohorts based on the predicted TRD risk of 80%. In a second step, we re-evaluated TRD, DFS and OS of both cohorts according to a further stratification based on 47.3 points of CCI cut-off., Results: In the low-risk cohort, we observed a significantly better DFS (84% vs. 46%, p<0.001), TRD (3% vs. 26%, p<0.001) and OS (89% vs. 62%, p<0.001) in the group with CCI < 47.3. In the high-risk cohort, patients with CCI < 47.3 had significantly better DFS (50% vs. 23%, p = 0.003) and OS (68% vs. 42%, p = 0.02) and a comparable TRD (22% vs. 31%, p = 0.142)., Conclusions: A complicated postoperative course negatively influenced long-term survival. This poorer oncological outcome associated with in-hospital postoperative complications suggests that every effort should be made to improve the early posttransplant course in HCC patients, including a careful donor-to recipient match and use of new perfusion technologies., Competing Interests: Conflict of Interest We have no conflicts of interest to disclose., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Despite second-line transplant(SLT) for recurrent hepatocellular carcinoma(rHCC) leads to the longest survival after recurrence(SAR), its real applicability has never been reported. The aim was to compare the SAR of SLT versus repeated hepatectomy and thermoablation(CUR group)., Methods: Patients were enrolled from the Italian register HE.RC.O.LE.S. between 2008 and 2021. Two groups were created: CUR versus SLT. A propensity score matching (PSM) was run to balance the groups., Results: 743 patients were enrolled, CUR = 611 and SLT = 132. Median age at recurrence was 71(IQR 6575) years old and 60(IQR 53-64, p < 0.001) for CUR and SLT respectively. After PSM, median SAR for CUR was 43 months(95%CI = 37 - 93) and not reached for SLT(p < 0.001). SLT patients gained a survival benefit of 9.4 months if compared with CUR. MilanCriteria(MC)-In patients were 82.7% of the CUR group. SLT(HR 0.386, 95%CI = 0.23 - 0.63, p < 0.001) and the MELD score(HR 1.169, 95%CI = 1.07 - 1.27, p < 0.001) were the only predictors of mortality. In case of MC-Out, the only predictor of mortality was the number of nodules at recurrence(HR 1.45, 95%CI= 1.09 - 1.93, p = 0.011)., Conclusion: It emerged an important transplant under referral in favour of repeated hepatectomy or thermoablation. In patients with MC-Out relapse, the benefit of SLT over CUR was not observed., Competing Interests: Conflict of interest None., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Widespread use of minimally invasive liver surgery (MILS) contributed to the reduction of surgical risk of liver resection for hepatocellular carcinoma (HCC). Aim of this study was to analyze outcomes of MILS for single ≤3 cm HCC., Methods: Patients who underwent MILS for single ≤3 cm HCC (November 2014 - December 2019) were identified from the Italian Group of Minimally Invasive Liver Surgery (IGoMILS) Registry., Results: Of 714 patients included, 641 (93.0%) were Child-Pugh A; 65.7% were limited resections and 2.2% major resections, with a conversion rate of 5.2%. Ninety-day mortality rate was 0.3%. Overall morbidity rate was 22.4% (3.8% major complications). Mean postoperative stay was 5 days. Robotic resection showed longer operative time (p = 0.004) and a higher overall morbidity rate (p < 0.001), with similar major complications (p = 0.431). Child-Pugh B patients showed worse mortality (p = 0.017) and overall morbidity (p = 0.021), and longer postoperative stay (p = 0.005). Five-year overall survival was 79.5%; cirrhosis, satellite micronodules, and microvascular invasion were independently associated with survival., Conclusions: MILS for ≤3 cm HCC was associated with low morbidity and mortality rates, showing high safety, and supporting the increasing indications for surgical resection in these patients., Competing Interests: Conflicts of interest None to declare., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with unresectable Colorectal Liver Metastases (CLM) receiving palliative chemotherapy have a 5-year overall survival (OS) of less than 30%. Liver transplantation (LT) can improve OS up to 60%-83% (SECA-I and SECA-II trials). The aim of the study is to assess the efficacy of LT in liver-only metastatic CRC compared with a matched cohort of patients included in a phase III trial on triplet chemotherapy + antiEGFR., Patients and Methods: The COLT trial is an investigator-driven, multicenter, non-randomized, open-label, controlled, prospective, parallel trial (ClinicalTrials.gov NCT03803436). Hyperselected patients with liver-limited unresectable CLM, RAS and BRAF wild-type and curatively removed primary colon cancer are included. The observed post-transplant outcomes will be prospectively compared 1:5 with those obtained in a matched cohort from the TRIPLETE trial (NCT03231722)., Results: Primary endpoint is to compare the 3 and 5-years OS of patients enrolled in the COLT trial with COLT-eligible population enrolled in the TRIPLETE trial. An expected gain in OS of 40% at 5-years is predicted for the COLT population (the expected OS at 5-years in COLT vs. TRIPLETE is 70% vs. 30%). Secondary endpoints are to compare the 5-years disease-free survival and to assess the safety of LT (Dindo-Clavien Classification and the Comprehensive Complication Index)., Conclusion: LT offers the longest OS reported in selected patients with CLM. Improving the selection strategies can give patients a 5-year OS similar to other indications for LT and a better outcome than those undergoing chemotherapy alone., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Over the last decades relevant epidemiological changes of liver diseases have occurred, together with greatly improved treatment opportunities., Aim: To investigate how the indications for elective adult liver transplantation and the underlying disease etiologies have evolved in Italy., Methods: We recruited from the National Transplant Registry a cohort comprising 17,317 adults patients waitlisted for primary liver transplantation from January-2004 to December-2020. Patients were divided into three Eras:1(2004-2011),2(2012-2014) and 3(2015-2020)., Results: Waitlistings for cirrhosis decreased from 65.9% in Era 1 to 46.1% in Era 3, while those for HCC increased from 28.7% to 48.7%. Comparing Eras 1 and 3, waitlistings for HCV-related cirrhosis decreased from 35.9% to 12.1%, yet those for HCV-related HCC increased from 8.5% to 26.7%. Waitlistings for HBV-related cirrhosis remained almost unchanged (13.2% and 12.4%), while those for HBV-related HCC increased from 4.0% to 11.6%. ALD-related cirrhosis decreased from 16.9% to 12.9% while ALD-related HCC increased from 1.9% to 3.9%., Conclusions: A sharp increase in liver transplant waitlisting for HCC and a concomitant decrease of waitlisting for cirrhosis have occurred In Italy. Despite HCV infection has noticeably decreased, still remains the primary etiology of waitlisting for HCC, while ALD and HBV represent the main causes for cirrhosis., (Copyright © 2022. Published by Elsevier Ltd.)

A short period (1-2 h) of hypothermic oxygenated machine perfusion (HOPE) after static cold storage is safe and reduces ischemia-reperfusion injury-related complications after liver transplantation. Machine perfusion time is occasionally prolonged for logistical reasons, but it is unknown if prolonged HOPE is safe and compromises outcomes. We conducted a multicenter, observational cohort study of patients transplanted with a liver preserved by prolonged (≥4 h) HOPE. Postoperative biochemistry, complications, and survival were evaluated. The cohort included 93 recipients from 12 European transplant centers between 2014-2021. The most common reason to prolong HOPE was the lack of an available operating room to start the transplant procedure. Grafts underwent HOPE for a median (range) of 4:42 h (4:00-8:35 h) with a total preservation time of 10:50 h (5:50-20:50 h). Postoperative peak ALT was 675 IU/L (interquartile range 419-1378 IU/L). The incidence of postoperative complications was low, and 1-year graft and patient survival were 94% and 88%, respectively. To conclude, good outcomes are achieved after transplantation of donor livers preserved with prolonged (median 4:42 h) HOPE, leading to a total preservation time of almost 21 h. These results suggest that simple, end-ischemic HOPE may be utilized for safe extension of the preservation time to ease transplantation logistics., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Competing Interests: Conflict of interest None declared.

There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013-2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65.6% male, median [IQR] age: 47 [42-56] years). Forty-five of 93 patients received corticosteroids, 52 of 93 were non-responders and among these, 20 patients were waitlisted. Sixteen patients underwent LT. Overall, 6-, 12-, and 24-month survival rates were 100% significantly higher compared with non-responders to medical therapy who were denied LT (45%, 45%, and 36%; p < .001). 2/16 patients resumed alcohol intake, one at 164 days and one at 184 days. Early LT significantly improves survival in sAH non-responding to medical therapy, when a strict selection process is applied. Further studies are needed to properly assess alcohol relapse rates., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background & Aims: In Italy, since August 2014, liver transplant (LT) candidates with model for end-stage liver disease (MELD) scores ≥30 receive national allocation priority. This multicenter cohort study aims to evaluate time on the waiting list, dropout rate, and graft survival before and after introducing the macro-area sharing policy., Methods: A total of 4,238 patients registered from 2010 to 2018 were enrolled and categorized into an ERA-1 Group (n = 2,013; before August 2014) and an ERA-2 Group (n = 2,225; during and after August 2014). A Cox proportional hazards model was used to estimate the hazard ratio (HR) of receiving a LT or death between the two eras. The Fine-Gray model was used to estimate the HR for dropout from the waiting list and graft loss, considering death as a competing risk event. A Fine-Gray model was also used to estimate risk factors of graft loss., Results: Patients with MELD ≥30 had a lower median time on the waiting list (4 vs.12 days, p <0.001) and a higher probability of being transplanted (HR 2.27; 95% CI 1.78-2.90; p = 0.001) in ERA-2 compared to ERA-1. The subgroup analysis on 3,515 LTs confirmed ERA-2 (odds ratio 0.56; 95% CI 0.46-0.68; p = 0.001) as a protective factor for better graft survival rate. The protective variables for lower dropouts on the waiting list were: ERA-2, high-volume centers, no competition centers, male recipients, and hepatocellular carcinoma. The protective variables for graft loss were high-volume center and ERA-2, while MELD ≥30 remained related to a higher risk of graft loss., Conclusions: The national MELD ≥30 priority allocation was associated with improved patient outcomes, although MELD ≥30 was associated with a higher risk of graft loss. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes., Clinical Trial Number: NCT04530240 LAY SUMMARY: Italy introduced a new policy in 2014 to give national allocation priority to patients with a model for end-stage liver disease (MELD) score ≥30 (i.e. very sick patients). This policy has led to more liver transplants, fewer dropouts, and shorter waiting times for patients with MELD ≥30. However, a higher risk of graft loss still burdens these cases. Transplant center volumes and competition among centers may have a role in recipient prioritization and outcomes., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: The concept of benchmarking is established in the field of transplant surgery; however, benchmark values for donation after circulatory death (DCD) liver transplantation are not available. Thus, we aimed to identify the best possible outcomes in DCD liver transplantation and to propose outcome reference values., Methods: Based on 2,219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1,012 low-risk, primary, adult liver transplantations with a laboratory MELD score of ≤20 points, receiving a DCD liver with a total donor warm ischemia time of ≤30 minutes and asystolic donor warm ischemia time of ≤15 minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the comprehensive complication index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75 th -percentile was considered., Results: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centres. The 1-year retransplant and mortality rates were 4.5% and 8.4% in the benchmark group, respectively. Within the first year of follow-up, 51.1% of recipients developed at least 1 major complication (≥Clavien-Dindo-Grade III). Benchmark cut-offs were ≤3 days and ≤16 days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade III), ≤16.8% for ischemic cholangiopathy, and ≤38.9 CCI points 1 year after transplant. Comparisons with higher risk groups showed more complications and impaired graft survival outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk., Conclusions: Despite excellent 1-year survival, morbidity in benchmark cases remains high. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups and to provide a valid comparator cohort for future clinical trials., Lay Summary: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2,219 liver transplantations following controlled DCD donation in 17 centres worldwide. Donor and recipient combinations with higher risk had significantly worse outcomes. However, the use of novel organ perfusion technology helped high-risk patients achieve similar outcomes as the benchmark cohort., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool., (© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: Optimal treatment of hepatocellular carcinoma (HCC) beyond the Milan criteria (MC) is debated. The aim of the study was to assess overall-survival (OS) and disease-free-survival (DFS) for HCC beyond MC when treated by trans-arterial-chemoembolization (TACE) or surgical resection (SR)., Method: between 2005 and 2015, all patients with a first diagnosis of HCC beyond MC(1 nodule>5 cm, or 3 nodules>3 cm without macrovascular invasion) were evaluated. Analyses were carried out through Kaplan-Meier, Cox models and the inverse probability weighting (IPW) method to reduce allocation bias. Sub-analyses have been performed for multinodular and single large tumors compared with a MC-IN cohort., Results: 226 consecutive patients were evaluated: 118 in SR group and 108 in TACE group. After IPW, the two pseudo-populations were comparable for tumor burden and liver function. In the SR group, 1-5 years OS rates were 72.3% and 35% respectively and 92.7% and 39.3% for TACE (p = 0.500). The median DFS was 8 months (95%CI:8-9) for TACE, and 11 months (95%CI:9-12) for SR (p < 0.001). TACE was an independent predictor for recurrence (HR 1.5; 95%CI: 1.1-2.1; p = 0.015). Solitary tumors > 5 cm and multinodular disease had comparable OS and DFS as Milan-IN group (p > 0.05)., Conclusion: Surgery allowed a better control than TACE in patient bearing HCC beyond MC. This translated into a significant benefit in terms of DFS but not OS., (Copyright © 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: In the context of liver transplantation (LT) for hepatocellular carcinoma (HCC), prediction models are used to ensure that the risk of post-LT recurrence is acceptably low. However, the weighting that 'response to neoadjuvant therapies' should have in such models remains unclear. Herein, we aimed to incorporate radiological response into the Metroticket 2.0 model for post-LT prediction of "HCC-related death", to improve its clinical utility., Methods: Data from 859 transplanted patients (2000-2015) who received neoadjuvant therapies were included. The last radiological assessment before LT was reviewed according to the modified RECIST criteria. Competing-risk analysis was applied. The added value of including radiological response into the Metroticket 2.0 was explored through category-based net reclassification improvement (NRI) analysis., Results: At last radiological assessment prior to LT, complete response (CR) was diagnosed in 41.3%, partial response/stable disease (PR/SD) in 24.9% and progressive disease (PD) in 33.8% of patients. The 5-year rates of "HCC-related death" were 3.1%, 9.6% and 13.4% in those with CR, PR/SD, or PD, respectively (p <0.001). Log 10 AFP (p <0.001) and the sum of number and diameter of the tumour/s (p <0.05) were determinants of "HCC-related death" for PR/SD and PD patients. To maintain the post-LT 5-year incidence of "HCC-related death" <30%, the Metroticket 2.0 criteria were restricted in some cases of PR/SD and in all cases with PD, correctly reclassifying 9.4% of patients with "HCC-related death", at the expense of 3.5% of patients who did not have the event. The overall/net NRI was 5.8., Conclusion: Incorporating the modified RECIST criteria into the Metroticket 2.0 framework can improve its predictive ability. The additional information provided can be used to better judge the suitability of candidates for LT following neoadjuvant therapies., Lay Summary: In the context of liver transplantation for patients with hepatocellular carcinoma, prediction models are used to ensure that the risk of recurrence after transplantation is acceptably low. The Metroticket 2.0 model has been proposed as an accurate predictor of "tumour-related death" after liver transplantation. In the present study, we show that its accuracy can be improved by incorporating information relating to the radiological responses of patients to neoadjuvant therapies., Competing Interests: Conflict of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

In January 2020, Novel Coronavirus Disease 2019 (COVID-19) resulted in a global pandemic, creating uncertainty toward the management of liver transplantation (LT) programs. Lombardy has been the most affected region in Italy: the current mortality rate of COVID-19 patients is 18.3% (10 022 deaths; April 10th) with hospitals in Lombardy having to expand the total number of ICU beds from 724 to 1381 to accommodate infected patients. There has been a drastic decrease in liver donors. From February 23rd until April 10th, 17 LTs were performed in Lombardy. Mean donor age was 49 years (range 18-74) whereas mean recipient age was 55 (13-69); mean MELD score was 12 (6-24). All donors underwent screening for SARS-CoV-2 prior to LT. Two patients tested positive after LT, and one patient died for COVID on POD 30. Sixteen patients are alive after an average of 30 days post-LT (range 3-46). 10 patients have been discharged. This study has found no specific reason concerning the safety of recipients, to stop LT programs. Several key lessons from our experience are reported. However, due to the complex circumstances which surround the viral outbreak, the cessation or a reduction in LT activity is a pragmatic requirement., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: A preoperative risk score (PRS) to predict outcome of patients with intrahepatic cholangiocarcinoma treated by liver surgery could be clinically relevant.To assess accuracy for broadly adoption, external validation of predictive models on independent datasets is crucial. The objective of this study was to externally validate the score for prediction of long-term outcomes after liver surgery for intrahepatic cholangiocarcinoma proposed by Sasaki et al. and based on preoperative albumin, neutrophil-to-lymphocytes-ratio, CA19-9 and tumor size., Methods: Patients treated by liver surgery for intrahepatic cholangiocarcinoma at 11 international HPB centers from 2001 to 2018 were included in the external validation cohort. Harrell's c-index and Hosmer-Lemeshow analyses were used to test PRS discrimination and calibration. Kaplan-Meier curve for risk groups as described in the original study were displayed., Results: A total of 355 patients with 174 deaths during the follow-up period (median = 41.7 months, IQR 32.8-50.6) were included. The median PRS value was 14.7 (IQR 10.7-20.6), with normal distribution across the cohort. A Cox regression on PRS covariates found coefficients similar to those of the derivation cohort, except for tumor size. Measures of discrimination estimated by Harrell's c-index was 0.61(95%CI:0.56-0.67) and Hosmer-Lemeshow p = 0.175. The Kaplan-Meyer estimation showed reasonable discrimination across risk groups, with 5years survival rate ranging from 20.1% to 0%., Conclusion: In this external validation cohort, the PRS had mild discrimination and poor calibration performance, similarly to the original publication. Nevertheless, its ability to identify different classes of risk is clinically useful, for a better tailoring of a therapeutic strategy., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Introduction: Patients with a single small Hepatocellular Carcinoma (HCC) may be definitively treated by Radiofrequency ablation (RFA) with a very low rate of peri-operative morbidity. However, results are still controversial comparing RFA to Liver Resection (LR)., Methods: All consecutive patients treated by RFA or LR for a single untreated small HCC on liver cirrhosis between January 2006-December 2016 were enrolled. Patients were matched 1:1 basing on: age, MELD-score, platelet count, nodule's diameter, HCV status, α-fetoprotein level, and Albumin-Bilirubin score. First analysis compered LR to RFA. Second analysis compared Laparoscopic LR (LLR) to RFA., Results: Of 484 patients with single small HCC, 91 patients were selected for each group after a 1:1 propensity score matching (PS-M). The 5-years OS was 70% and 60% respectively for LR and RFA group (P = 0.666). The 5-year RFS was 36% and 21% respectively for LR and RFA group (P < 0.001). Patients treated by LR had a significantly longer hospital stay and higher complications rate. Comparing 50 cases of LLR and 50 of RFA, the 5-years OS was 79% and 56% respectively for LLR and RFA group (P = 0.22). The 5-year RFS was 54% and 19% respectively for LR and RFA group (P < 0.001). Post-operative complications were not significantly different., Conclusions: LLR confers similar peri-operative complications rate compared to RFA. LLR should be considered as a first-line approach for the treatment of a single small HCC as it combines the effectiveness of open LR and the safety profile of RFA., (Copyright © 2019 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50 years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially "splittable" donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P = .009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P = .045]). The pediatric (4.5% vs 2.5% [P = .398]) and adult (9.7% to 5.2% [P < .001]) LT-waiting list mortality reduced; SLT outcomes remained stable. Retransplantation (HR = 2.641, P = .035) and recipient weight >20 kg (HR = 5.113, P = .048) in LLS, and ischemic time >8 hours (HR = 2.475, P = .048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: The extent of liver resection for the optimal treatment of hepatocellular carcinoma (HCC) is debated. The purpose of this study was to compare the impact of anatomic resection (AR) vs. parenchyma-sparing resection (PSR) on disease recurrence and patient survival., Methods: We retrospectively analyzed patients with HCC who underwent liver resection from January 2001 to August 2015. Patients receiving AR or PSR were compared by a propensity score analysis (PSA) (caliper = 0.1). The primary outcomes were disease-free survival (DFS) and overall survival (OS) rates, and assessed by the Kaplan-Meier method., Results: 455 consecutive patients were evaluated. After PSA 354 patient were studied (177 pairs for each group). The median follow-up time was 28.2 months. The median OS was 47.5 months (95% CI: 30.0-65.9) for AR and 56.5 months (95% CI 33.2-79.6) for PSR (p = 0.169). The median DFS was 29.2 months (95% CI 17.6-40.8) for AR and 24.8 months (95% CI: 15.2-34.2) for PSR (p = 0.337). The multivariate regression model showed that cirrhosis (HR 2.85, 95% CI: 1.53-5.32; p = 0.001), BCLC grade B (HR 4.15, 95% CI: 1.33-12.95; p = 0.014), microvascular invasion (HR 1.55, 95% CI: 1.03-2.31; p = 0.033), presence of satellitosis (HR 1.94, 95% CI: 1.25-3.01; p = 0.003), severe complications (HR 6.09, 95% CI: 2.26-16.40; p > 0.001) were independently associated with poor long-term oncologic outcomes., Conclusions: The extent of resection did not significantly affect overall and disease-free survival while tumor characteristics and underlying liver function appeared significant determinants., (Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background & Aims: Direct-acting antivirals (DAAs) have dramatically improved the outcome of patients with hepatitis C virus (HCV) infection including those with decompensated cirrhosis (DC). We analyzed the evolution of indications and results of liver transplantation (LT) in the past 10 years in Europe, focusing on the changes induced by the advent of DAAs., Methods: This is a cohort study based on data from the European Liver Transplant Registry (ELTR). Data of adult LTs performed between January 2007 to June 2017 for HCV, hepatitis B virus (HBV), alcohol (EtOH) and non-alcoholic steatohepatitis (NASH) were analyzed. The period was divided into different eras: interferon (IFN/RBV; 2007-2010), protease inhibitor (PI; 2011-2013) and second generation DAA (DAA; 2014-June 2017)., Results: Out of a total number of 60,527 LTs, 36,382 were performed in patients with HCV, HBV, EtOH and NASH. The percentage of LTs due to HCV-related liver disease varied significantly over time (p <0.0001), decreasing from 22.8% in the IFN/RBV era to 17.4% in the DAA era, while those performed for NASH increased significantly (p <0.0001). In the DAA era, the percentage of LTs for HCV decreased significantly (p <0.0001) from 21.1% (first semester 2014) to 10.6% (first semester 2017). This decline was more evident in patients with DC (HCV-DC, -58.0%) than in those with hepatocellular carcinoma (HCC) associated with HCV (HCV-HCC, -41.2%). Conversely, three-year survival of LT recipients with HCV-related liver disease improved from 65.1% in the IFN/RBV era to 76.9% in the DAA era, and is now comparable to the survival of recipients with HBV infection (p = 0.3807)., Conclusions: In Europe, the number of LTs due to HCV infection is rapidly declining for both HCV-DC and HCV-HCC indications and post-LT survival has dramatically improved over the last three years. This is the first comprehensive study of the overall impact of DAA treatment for HCV on liver transplantation in Europe., Lay Summary: After the advent of direct-acting antivirals in 2014, a dramatic decline was observed in the number of liver transplants performed both in patients with decompensated cirrhosis due to hepatitis C virus (HCV), minus 60%, and in those with hepatocellular carcinoma associated with HCV, minus 41%. Furthermore, this is the first large-scale study demonstrating that the survival of liver transplant recipients with HCV-related liver disease has dramatically improved over the last three years and is now comparable to the survival of recipients with hepatitis B virus infection. The reduction in HCV-related indications for LT means that there is a greater availability of livers, at least 600 every year, which can be allocated to patients with indications other than HCV., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background: The purpose of the study was to evaluate whether the mutational status of Kirsten rat sarcoma viral oncogene homolog (KRAS) or b-viral oncogene homolog B1 (BRAF) could be an independent prognostic factor in the subset of patients with colorectal cancer liver metastases (CRLM) who undergo complete liver resection., Materials and Methods: A systematic literature review was performed to identify articles reporting relapse-free survival (RFS) and/or overall survival (OS) of patients who underwent complete liver resection for CRLM, stratified according to KRAS and BRAF mutational status. Hazard ratios (HRs) from multivariate analyses were pooled in the meta-analysis., Results: Eleven studies, including 1833 patients, were eligible for the meta-analysis. Nine of them reported OS stratified according to KRAS mutation. The pooled analysis revealed that KRAS mutation was negatively associated with OS (HR, 1.674; 95% confidence interval [CI], 1.341-2.089; P < .001). Nine among 11 studies reported RFS stratified according to KRAS mutation and HRs in multivariate analysis were available in 7. In a pooled analysis, KRAS mutation was negatively associated with RFS (HR, 1.529; 95% CI, 1.287-1.817; P < .001). In 3 studies HRs of the multivariate analysis regarding the OS according to BRAF mutational status were also available, showing a negative association with OS (HR, 3.055; 95% CI, 1.794-5.204; P < .001)., Conclusion: KRAS mutations are negatively associated with OS and RFS in patients who undergo complete liver resection for CRLM. A similar negative effect on OS was observed also for BRAF mutation, although fewer studies were included. These data support integration of KRAS and BRAF mutational status into a combined predictive score for prospective assessment of outcome after resection of CRLM in clinical studies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background & Aims: The current organ allocation system for liver transplantation (LT) creates an imbalance between patients with and without hepatocellular carcinoma (HCC). We describe a model designed to re-establish allocation equity among patient groups using transplant benefit as the common endpoint., Methods: We enrolled consecutive adult patients entering the waiting list (WL group, n=2697) and undergoing LT (LT group, n=1702) during the period 2004-2009 in the North Italy Transplant program area. Independent multivariable regressions (WL and LT models) were created for patients without HCC and for those with stage T2 HCC. Monte Carlo simulation was used to create distributions of transplant benefit, and covariates such as Model for End-stage Liver Disease (MELD) and alpha-fetoprotein (AFP) were combined in regression equations. These equations were then calibrated to create an "MELD equivalent" which matches HCC patients to non-HCC patients having the same numerical MELD score., Results: Median 5 year transplant benefit was 15.12 months (8.75-25.35) for the non-HCC patients, and 28.18 months (15.11-36.38) for the T2-HCC patients (p<0.001). Independent predictors of transplant benefit were MELD score (estimate=0.89, p<0.001) among non-HCC patients, and MELD (estimate=1.14, p<0.001) and logAFP (estimate=-0.46, p<0.001) among HCC patients. The equation "HCC-MELD"=1.27∗MELD - 0.51∗logAFP+4.59 calculates a numerical score for HCC patients, whereby their transplant benefit is equal to that of non-HCC patients with the same numerical value for MELD., Conclusions: We describe a method for calibrating HCC and non-HCC patients according to survival benefit, and propose that this method has the potential, if externally validated, to restore equity to the organ allocation system., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Hepatic pedicle clamping (HPC) during Liver Resection (LR) is a vascular procedure designed to prevent bleeding from the liver during hepatectomy. Outgrowth of pre-existing colorectal micrometastases may occur 5-6 times faster in occluded liver lobes than in non-occluded lobes. We conducted a case-matched analysis at our Institution to assess the effects of HPC on overall and recurrence-free survival in highly selected patients, who underwent LR due to Colorectal liver metastases (CLM)., Materials and Methods: From January 2002 to December 2010, 120 patients operated for CLM were included into this case-matched study. Patients were allocated to two groups: Group-A patients who underwent HPC during LR; Group-B patients who underwent LR without HPC., Results: HPC during liver resection was associated with better overall patient 5-year survival (47.2% in Group-A and 32.1% in Group-B) (P-value = 0.06), and significantly better 5-year recurrence-free survival (49.9% in Group-A vs 18.3% in Group-B) (P-value = 0.010) The Cox regression model identified the following risk factors for worse prognosis in terms of shorter recurrence-free survival and higher incidence of tumor recurrence: no HPC (Group-B) (P-value = 0.032) and positive lymph nodes at the time of LR (P-value = 0.018)., Conclusion: Lack of HPC in selected patients who underwent LR for CLM results to be a strong independent risk factor for higher patient exposure to tumor recurrence. We suggest that hepatic hilum clamping should be seriously taken into consideration in this patient setting., Mini-Abstract: A case-matched study was performed in 120 patients undergoing liver resection due to colorectal liver metastases, comparing patients who received intermittent hepatic pedicle clamping (HPC) with those who did not. The 5-year overall survival rate was similar, but the 5-year recurrence-free rate was significantly higher with no HPC (p = 0.012)., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC group (6.1% vs. 13.3% in TAC Control, p = 0.010). Adjusted change in estimated glomerular filtration rate (eGFR) from randomization to month 24 was superior with EVR + Reduced TAC versus TAC Control: difference 6.7 mL/min/1.73 m(2) (97.5% CI 1.9, 11.4 mL/min/1.73 m(2), p = 0.002). Among patients who remained on treatment, mean (SD) eGFR at month 24 was 77.6 (26.5) mL/min/1.73 m(2) in the EVR + Reduced TAC group and 66.1 (19.3) mL/min/1.73 m(2) in the TAC Control group (p < 0.001). Study medication was discontinued due to adverse events in 28.6% of EVR + Reduced TAC and 18.2% of TAC Control patients. Early introduction of everolimus with reduced-exposure tacrolimus at 1 month after liver transplantation provided a significant and clinically relevant benefit for renal function at 2 years posttransplant., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

In a prospective, multicenter, open-label study, de novo liver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced-exposure tacrolimus (EVR+Reduced TAC) or (iii) standard-exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy-proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (-3.0%; 95% CI -8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m(2) , 97.5% CI 3.74, 13.27 mL/min/1.73 m(2) , p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Full-right-full-left split liver transplantation divides a donor liver into two grafts to be transplanted in adult-size patients. Major technical and organizational difficulties have limited its application to few single center series. We retrospectively analyzed the long-term results of the first multicenter series of this procedure with graft sharing. Between November 1998 and January 2005, 43 transplants were performed by five centers from 23 full-right-full-left in situ split liver procedures; 65% of the grafts were shared. A total of 31 (72%) patients had complications above grade II; 3 (6.9%) were retransplanted. Hospital mortality was 23% with sepsis as the main cause. Six patients died in the long term, two of them for a road accident. A total of 27 patients are alive after a median follow-up of 3200 days (2035-4256). Actuarial survival at 1 and 10 years were 72.1%, 62.6% and 65.1%, 57.9%, respectively for patients and grafts. These figures are similar to those reported for adult living donor liver transplantation by the European Registry over a similar period. Multicenter collaboration in sharing of these grafts is feasible and can help facing the organizational limits, thus increasing diffusion of full-right-full-left split liver transplantation., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Backgrounds/aims: We evaluated the effect of antiviral therapy on fibrosis progression in patients with histological features of mild/moderate HCV disease recurrence defined by a Grading score≥4 and Staging score up to 3 (Ishak) at 1 year after liver transplantation., Methods: Seventy-three consecutive patients with mild/moderate recurrence were randomized either to no treatment or to receive Pegilated-Interferon-alfa-2b and ribavirin for 52 weeks. Liver biopsies obtained at baseline (1 year after transplantation) and 2 years afterwards were evaluated for assessment of disease progression, defined as worsening of at least 2 staging points or progression to stage 4 or higher., Results: As for these two major histological end points there were no statistically significant differences between the 2 groups (36.1% vs. 50%, p=0.34 and 36.1% vs. 38.9%, p=1). Fifteen treated patients (41%) achieved a sustained virological response which was associated with a reduced risk of fibrosis worsening for both endpoints when compared to viremic patients (p=0.04)., Conclusions: Although antiviral-therapy was beneficial in preventing fibrosis progression in patients achieving a sustained virological response, the majority of the overall population of our patients with mild-moderate disease recurrence could not benefit from antiviral therapy either because they either could not be treated or did not respond to treatment (EudraCT number: 2005-005760)., (Copyright © 2012. Published by Elsevier Ltd.)

Until the present time, the first experimental liver transplant which led to the development of human liver transplantation is attributed to C. Stuart Welch who performed a heterotopic transplant in the canine species in 1955. In 1956, Jack Cannon is credited with the first animal orthotopic liver transplant although the species was not disclosed. This report is intended to set the historical record straight by acknowledging that Vittorio Staudacher in 1952 was the first to perform a liver transplant in a large animal model., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Donor-recipient match is a matter of debate in liver transplantation. D-MELD (donor age × recipient biochemical model for end-stage liver disease [MELD]) and other factors were analyzed on a national Italian database recording 5946 liver transplants. Primary endpoint was to determine factors predictive of 3-year patient survival. D-MELD cutoff predictive of 5-year patient survival <50% (5yrsPS<50%) was investigated. A prognosis calculator was implemented (http://www.D-MELD.com). Differences among D-MELD deciles allowed their regrouping into three D-MELD classes (A < 338, B 338-1628, C >1628). At 3 years, the odds ratio (OR) for death was 2.03 (95% confidence interval [CI], 1.44-2.85) in D-MELD class C versus B. The OR was 0.40 (95% CI, 0.24-0.66) in class A versus class B. Other predictors were hepatitis C virus (HCV; OR = 1.42; 95% CI, 1.11-1.81), hepatitis B virus (HBV; OR = 0.69; 95% CI, 0.51-0.93), retransplant (OR = 1.82; 95% CI, 1.16-2.87) and low-volume center (OR = 1.48; 95% CI, 1.11-1.99). Cox regressions up to 90 months confirmed results. The hazard ratio was 1.97 (95% CI, 1.59-2.43) for D-MELD class C versus class B and 0.42 (95% CI, 0.29-0.60) for D-MELD class A versus class B. Recipient age, HCV, HBV and retransplant were also significant. The 5yrsPS<50% cutoff was identified only in HCV patients (D-MELD ≥ 1750). The innovative approach offered by D-MELD and covariates is helpful in predicting outcome after liver transplantation, especially in HCV recipients., (©Copyright 2011 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation., Methods: Adult primary transplants performed with deceased heart-beating donors were included. Relevant information on donors and recipients, organ procurement and allocation were prospectively entered in an ad hoc database within the National Transplant Centre web-based Network. Data were blindly analysed by an independent Biostatistical Board., Results: The study enrolled 1530 donor/recipient matches. Median donor age was 56 years. Female donors (n = 681, median 58, range 12-92 years) were older than males (n = 849, median 53, range 2-97 years, p < 0.0001). Donors older than 60 years were 42.2%, including 4.2% octogenarians. Brain death was due to non-traumatic causes in 1126 (73.6%) cases. Half of the donor population was overweight, 10.1% was obese and 7.6% diabetic. Hepatitis B core antibody (HBcAb) was present in 245 (16.0%) donors. The median Donor Risk Index (DRI) was 1.57 (>1.7 in 35.8%). The median cold ischaemia time was 7.3h (≥ 10 in 10.6%). Median age of recipients was 54 years, and 77.7% were males. Hepatocellular carcinoma (HCC) was the most frequent indication overall (44.4%), being a coindication in roughly 1/3 of cases, followed by viral cirrhosis without HCC (28.2%) and alcoholic cirrhosis without HCC (10.2%). Hepatitis C virus infection (with or without HCC) was the most frequent etiologic factor (45.9% of the whole population and 71.4% of viral-related cirrhosis), yet hepatitis B virus infection accounted for 28.6% of viral-related cirrhosis, and HBcAb positivity was found in 49.7% of recipients. The median Model for End Stage Liver Disease (MELD) at transplant was 12 in patients with HCC and 18 in those without. Multivariate analysis showed a slight but significant inverse association between DRI and MELD at transplant., Conclusions: The deceased donor population in Italy has a high-risk profile compared to other countries, mainly due to older donor age. Almost half of the grafts are transplanted in recipients with HCC. Higher risk donors tend to be preferentially allocated to recipients with HCC, who are usually less ill and older. No other relevant allocation strategy is currently adopted at national level., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background/aims: Liver transplantation for endstage liver cirrhosis provides a useful model to investigate the pathogenetic role of hepatotropic viral agents. Recently, a new member of the Flaviviridae family, provisionally named HGV/GBV-C virus, has been associated with acute and chronic non A-E hepatitis. We studied 136 patients with cirrhosis consecutively transplanted at our institution for evidence of hepatitis G virus infection and correlation with the patients' clinical course., Methods: All patients survived for at least 6 months after transplantation (median follow-up 44 months) and underwent routine liver biopsies. Hepatitis G virus infection was studied using both direct viral RNA identification by RT-PCR and indirect detection of antibodies to the E2 glycoprotein., Results: There was a high frequency of the hepatitis G virus among patients undergoing liver transplantation, with HGV RNA and anti-E2 prevalence rates of 18.4% and 26.5%, respectively. HGV RNA prevalences significantly increased after transplantation (47.8%), with 47.3% rate of new infections in susceptible subjects. Anti-E2 antibodies were significantly more prevalent among patients transplanted for HCV-related cirrhosis and represented a strong protective factor against hepatitis G virus reinfection or recurrent infection. No correlation was found between HGV RNA or anti-E2 prevalences and survival after transplantation or rates of recurrent liver damage., Conclusions: All available evidence suggests that, although liver transplant patients are heavily exposed to hepatitis G virus both before and after transplantation, hepatitis G virus does not induce liver disease in this setting. Most infections appear to be self-limited and induce a protective immunity which is marked by the presence of anti-E2 antibodies.