Analysis of treatment benefits and prognostic factors for Post-Transplant hepatocellular carcinoma recurrence in a large Euro-American-Asian cohort.

BACKGROUND: Post-transplant HCC recurrence significantly impacts survival, yet its management is challenging due to limited evidence. With recent advancements in HCC treatment, updated data on managing recurrent disease is needed. METHODS: In this retrospective study across six centers (2000-2022), we employed Cox proportional-hazards regression and log-rank tests to assess survival differences. A prognostic score model was developed to categorize patient survival. Efficacy of tyrosine kinase inhibitors was evaluated through propensity score matching. RESULTS: In our study, 431 of 3349 (14%) transplanted HCC patients developed recurrence within a median interval of 18 (IQR:9-32) months. 147 (34%) underwent curative-intent treatments, 207 (48%) received palliative treatments, and 77 (18%) were given best-supportive care. Patients undergoing curative-intent treatments had better survival from the time of recurrence with median survival of 45 (95%CI:36-63) months and 1/3/5-year survival of 90%/56%/43% compared to those receiving non-curative treatments (median: 11 (95%CI:10-13) months, 1/3/5-year survival of 46%/10%/7%, log-rank p<0.001). Patients with recurrence diagnosed in the era 2018-2022 showed improved survival over previous era (HR 0.64 (95%CI:0.47-0.86)). Multivariable analysis identified 5 prognostic factors: ineligibility for curative-intent treatment (HR 3.5 (95%CI:2.7-4.6)), recurrence within 1-year (HR 1.7 (95%CI:1.3-2.1)), poor tumor differentiation (HR 1.5 (95%CI:1.1-1.9)), RETREAT score ≥3 (HR 1.4 (95%CI:1.1-1.8)) and AFP at recurrence ≥400 ng/mL (HR 1.4 (95%CI:1.1-1.9)). These factors contributed to a prognostic scoring system (0-9) that stratified patients into three prognosis groups. Both propensity score-matched analysis and multivariable regression indicated that lenvatinib was not statistically superior to sorafenib in terms of efficacy. CONCLUSION: Curative-intent treatments should be advocated for patients with post-transplant recurrence whenever possible. Prognostic factors linked to aggressive tumor biology significantly influence survival. Advancements in HCC management have improved survival outcomes over the past five years.

The long-term follow-up of the living liver donors.

Living donor liver transplantation (LDLT) has been proposed in many countries to reduce organ shortage. While the early postoperative outcomes have been well investigated, little is known about the long-term follow-up of the living donors. We, therefore, designed a systematic review of the literature to explore long-term complications and quality of life among living donors. We searched MEDLINE and EMBASE registries for studies published since 2013 that specifically addressed long-term follow-up following living-donor liver donation, concerning both physical and psychological aspects. Publications with a follow-up shorter than 1 year or that did not clearly state the timing of outcomes were excluded. A total of 2505 papers were initially identified. After a thorough selection, 17 articles were identified as meeting the eligibility criteria. The selected articles were mostly from North America and Eastern countries. Follow-up periods ranged from 1 to 11.5 years. The most common complications were incision site discomfort (13.2-38.8%) and psychiatric disorders (1-22%). Biliary strictures occurred in 1-14% of cases. Minimally invasive donor hepatectomy could improve quality of life, but long-term data are limited. About 30 years after the first reported LDLT, little has been published about the long-term follow-up of the living donors. Different factors may contribute to this gap, including the fact that, as healthy individuals, living donors are frequently lost during mid-term follow-up. Although the reported studies seem to confirm long-term donor safety, further research is needed to address the real-life long-term impact of this procedure.

Current role and perspectives of living donor liver transplantation for hepatocellular carcinoma: systematic review of the past 20 years.

Hepatocellular carcinoma (HCC) poses a significant global health challenge, and liver transplantation (LT) remains the best curative option. Living donor liver transplantation (LDLT) emerged as a potential solution to organ scarcity, reducing waitlist times. This comprehensive review explores LDLT practices, focusing on patient selection criteria and oncologic outcomes. A systematic review following PRISMA guidelines included 50 studies (2004-2023) with 8062 patients. Data encompassed baseline characteristics, HCC features, and oncologic outcomes. Further analysis categorized results by geography and publication year. Heterogeneity in patient demographics, tumor burden, and transplant characteristics was observed. Recent LDLT series demonstrated a shift towards refined selection criteria, increased neoadjuvant treatment, and improved oncologic outcomes. Geographic disparities revealed unique challenges in Eastern and Western practices. LDLT proves effective for HCC, addressing donor shortages. Evolving practices highlight the importance of refining inclusion criteria and optimizing tumor management. While geographic differences exist, LDLT, when judiciously applied, offers promising outcomes.

Dynamic surgical anatomy using 3D reconstruction technology in complex hepato-biliary surgery with vascular involvement. Results from an international multicentric survey.

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.

Computed Tomography and Magnetic Resonance Imaging Signs of Chronic Liver Rejection: A Case-Control Study.

OBJECTIVE: In liver transplantation, chronic rejection is still poorly studied. This study aimed to investigate the role of imaging in its recognition. METHODS: This study is a retrospective observational case-control series. Patients with histologic diagnosis of chronic liver transplant rejection were selected; the last imaging examination (computed tomography or magnetic resonance imaging) before the diagnosis was evaluated. At least 3 controls were selected for each case; radiological signs indicative of altered liver function were analyzed. χ 2 Test with Yates correction was used to compare the rates of radiologic signs in the case and control groups, also considering whether patients suffered chronic rejection within or after 12 months. Statistical significance was set at P < 0.050. RESULTS: A total of 118 patients were included in the study (27 in the case group and 91 in the control group). Periportal edema was appreciable in 19 of 27 cases (70%) and in 6 of 91 controls (4%) ( P < 0.001); ascites and hepatomegaly were present in 14 of 27 cases (52%) and 12 of 27 cases (44%), respectively, and in 1 of 91 controls (1%) ( P < 0.001); splenomegaly was present in 13 of 27 cases (48%) and in 8 of 91 controls (10%) ( P < 0.001); and biliary tract dilatation was present in 13 of 27 cases (48%) and in 11 of 91 patients controls (5%) ( P < 0.001). In the controls, periportal edema was significantly less frequent beyond 12 months after transplant (1% vs 11%; P = 0.020); the other signs after 12 months were not significant. CONCLUSIONS: The identification of periportal edema, biliary dilatation, ascites, and hepatosplenomegaly can serve as potential warning signs of ongoing chronic liver rejection. It is especially important to investigate periportal edema if it is present 1 year or more after orthotopic liver transplantation.

Improving outcomes of in situ split liver transplantation in Italy over the last 25 years.

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.

The impact of postoperative complications on oncological outcomes of liver transplantation for hepatocellular carcinoma: A competing risk analysis.

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.

Robotic Versus Laparoscopic Donor Nephrectomy: A Retrospective Bicentric Comparison of Learning Curves and Surgical Outcomes From 2 High-volume European Centers.

BACKGROUND: Although laparoscopic donor nephrectomy (LDN) represents the gold-standard technique for kidney living donation, robotic donor nephrectomy (RDN) settled as another appealing minimally invasive technique over the past decades. A comparison between LDN and RDN outcomes was performed. METHODS: RDN and LDN outcomes were compared, focusing on operative time and perioperative risk factors affecting surgery duration. Learning curves for both techniques were compared through spline regression and cumulative sum models. RESULTS: The study analyzed 512 procedures (154 RDN and 358 LDN procedures) performed between 2010 and 2021 in 2 different high-volume transplant centers. The RDN group presented a higher prevalence of arterial variations (36.2 versus 22.4%; P = 0.001) compared with the LDN cohort. No open conversions occurred; operative time (210 versus 195 min; P = 0.011) and warm ischemia time (WIT; 230 versus 180 s; P < 0.001) were longer in RDN. Postoperative complication rate was similar (8.4% versus 11.5%; P = 0.49); the RDN group showed shorter hospital stay (4 versus 5 d; P < 0.001). Spline regression models depicted a faster learning curve in the RDN group ( P = 0.0002). Accordingly, cumulative sum analysis highlighted a turning point after about 50 procedures among the RDN cohort and after about 100 procedures among the LDN group.Higher body mass index resulted as an independent risk factor for longer operative time for both techniques; multiple arteries significantly prolonged operative time in LDN, whereas RDN was longer in right kidney procurements; both procedures were equally shortened by growing surgical experience. CONCLUSIONS: RDN grants a faster learning curve and improves multiple vessel handling. Incidence of postoperative complications was low for both techniques.

Surgical Treatment of Hepatocellular Carcinoma: Multicenter Competing-risk Analysis of Tumor-related Death Following Liver Resection and Transplantation Under an Intention-to-treat Perspective.

BACKGROUND: Early-stage hepatocellular carcinoma could benefit from upfront liver resection (LR) or liver transplantation (LT), but the optimal strategy in terms of tumor-related outcomes is still debated. We compared the oncological outcomes of LR and LT for hepatocellular carcinoma, stratifying the study population into a low-, intermediate-, and high-risk class according to the risk of death at 5-y predicted by a previously developed prognostic model. The impact of tumor pathology on oncological outcomes of low- and intermediate-risk patients undergoing LR was investigated as a secondary outcome. METHODS: We performed a retrospective multicentric cohort study involving 2640 patients consecutively treated by LR or LT from 4 tertiary hepatobiliary and transplant centers between 2005 and 2015, focusing on patients amenable to both treatments upfront. Tumor-related survival and overall survival were compared under an intention-to-treat perspective. RESULTS: We identified 468 LR and 579 LT candidates: 512 LT candidates underwent LT, whereas 68 (11.7%) dropped-out for tumor progression. Ninety-nine high-risk patients were selected from each treatment cohort after propensity score matching. Three and 5-y cumulative incidence of tumor-related death were 29.7% and 39.5% versus 17.2% and 18.3% for LR and LT group ( P = 0.039), respectively. Low-risk and intermediate-risk patients treated by LR and presenting satellite nodules and microvascular invasion had a significantly higher 5-y incidence of tumor-related death (29.2% versus 12.5%; P < 0.001). CONCLUSIONS: High-risk patients showed significantly better intention-to-treat tumor-related survival after upfront LT rather than LR. Cancer-specific survival of low- and intermediate-risk LR patients was significantly impaired by unfavorable pathology, suggesting the application of ab-initio salvage LT in such scenarios.

Clinical Impact of Spontaneous Portosystemic Shunts in Liver Transplantation: A Comprehensive Assessment Through Total Shunt Area Measurement.

BACKGROUND: The impact of spontaneous portosystemic shunts (SPSSs) on natural history of cirrhotic patients was recently evaluated through the measurement of total shunt area (TSA), a novel tool that allows a comprehensive assessment of SPSSs extension, identifying a direct correlation of higher TSA with lower patient survival. The role of SPSSs in liver transplant (LT) is still debated: we sought to investigate the clinical impact of TSA on the development of early allograft dysfunction (EAD), acute kidney injury (AKI), postoperative complications, and graft and patient survival following LT. METHODS: Preoperative imaging of 346 cirrhotic patients undergoing primary LT between 2015 and 2020 were retrospectively revised, recording the size and anatomy of each SPSS to calculate TSA. The impact of TSA and selected patient and donor characteristics on the development of EAD, AKI, and clinically relevant complications was evaluated through univariate and multivariate logistic regression, whereas their effect on graft and patient survival was investigated through Cox regression analysis. RESULTS: A TSA exceeding 78.54 mm 2 resulted as an independent risk factor for the development of EAD (odds ratio [OR]: 2.327; P = 0.003), grade 3 AKI (OR: 2.093; P = 0.041), and clinically relevant complications (OR: 1.962; P = 0.015). Moreover, higher TSA was significantly related to early graft and patient survivals, emerging as an independent risk factor for 12-mo graft loss (hazard ratio: 3.877; P = 0.007) and patient death (hazard ratio: 2.682; P = 0.018). CONCLUSIONS: Higher TSA emerged as a significant risk factor for worse postoperative outcomes following LT, supporting the need for careful hemodynamic assessment and management of patients presenting multiple/larger shunts.

Current practice of normothermic regional perfusion and machine perfusion in donation after circulatory death liver transplants in Italy.

BACKGROUND: Normothermic regional perfusion (NRP) and machine perfusion (MP) are variously used in many European centers to improve the outcomes after liver transplantation from donation after circulatory death (DCD). In Italy, a combination of NRP and subsequent MP has been used since the start of the activity. While NRP is mandatory for every DCD recovery, the subsequent use of MP is left to each center. METHODS: We have designed a national survey to investigate practices and policies of these techniques. The questionnaire included 46 questions and was distributed to all the 21 Italian centers using an online form between June and July 2021. RESULTS: The overall response rate was 100%. A local NRP program for controlled Maastricht type 3 DCD was active in 11/21 (52.4%) centers. Organization and availability of personnel were perceived as the main difficulties in starting such a program. Between 2015 and 2020, 119 DCD livers were transplanted, with an overall utilization rate of 69.2%. Pump flow and gross aspect were considered the most reliable parameters in liver selection during NRP. Eight (72.7%) centers adopted subsequent hypothermic MP, 1 (9.1%) center normothermic MP, and the remaining 2 (18.2%) used both MP types. CONCLUSION: This first snapshot survey shows that NRP with subsequent MP is the most used protocol in Italy for DCD livers, although some heterogeneity exists in the type and purpose of MP between centers. Overall, this policy ensures a high utilization rate, considering the high risk of the DCD donor population in Italy.

From LI-RADS Classification to HCC Pathology: A Retrospective Single-Institution Analysis of Clinico-Pathological Features Affecting Oncological Outcomes after Curative Surgery.

Background: The latest Liver Imaging Reporting and Data System (LI-RADS) classification by the American College of Radiology has been recently endorsed in the American Association for the Study of Liver Disease (AASLD) guidelines for Hepatocellular carcinoma (HCC) management. Although the LI-RADS protocol has been developed as a diagnostic algorithm, there is some evidence concerning a possible correlation between different LI-RADS classes and specific pathological features of HCC. We aimed to investigate such radiological/pathological correlation and the possible prognostic implication of LI-RADS on a retrospective cohort of HCC patients undergoing surgical resection. Methods: We performed a retrospective analysis of the pathological characteristics of resected HCC, exploring their distribution among different LI-RADS classes and analyzing the risk factors for recurrence-free, overall and cancer-specific survival Results: LI-RADS-5 (LR-5) nodules showed a higher prevalence of microvascular invasion (MVI), satellitosis and capsule infiltration, as well as higher median values of alpha-fetoprotein (αFP) compared to LI-RADS-3/4 (LR-3/4) nodules. MVI, αFP, satellitosis and margin-positive (R1) resection resulted as independent risk factors for recurrence-free survival, while LI-RADS class did not exert any significant impact. Focusing on overall survival, we identified patient age, Eastern Cooperative Oncology Group performance status (ECOG-PS), Model for End Stage Liver Disease (MELD) score, αFP, MVI, satellitosis and R1 resection as independent risk factors for survival, without any impact of LI-RADS classification. Last, MELD score, log10αFP, satellitosis and R1 resection resulted as independent risk factors for cancer-specific survival, while LI-RADS class did not exert any significant impact. Conclusions: Our results suggest an association of LR-5 class with unfavorable pathological characteristics of resected HCC; tumor histology and underlying patient characteristics such as age, ECOG-PS and liver disease severity exert a significant impact on postoperative oncological outcomes.

Portal Steal Syndrome From a Large Linton's Splenorenal Shunt after Liver Transplantation: Successful Endovascular Management Through Off-Label Application of a 30 mm Amplatzer Cardiac Plug.

A 34-year-old patient underwent liver transplantation for progressive hepatic failure in the setting of congenital hepatic fibrosis. In past medical history, the patient had undergone splenectomy with proximal Linton's splenorenal surgical shunt creation for symptomatic portal hypertension with hypersplenism. The patient developed an early allograft dysfunction, with radiologic evidence of a reduced portal flow associated to portal steal from the patent surgical shunt. The patient was successfully treated through endovascular placement of a 30 mm Amplatzer cardiac plug at the origin of the splenic vein.

Discovery of a Rare Variant of the Arc of Bühler During Liver Procurement.

We report a rare variant of the hepatic arterial supply observed during liver procurement from a 71-year-old female donor for whom an ischemic stroke caused brain death. Preoperative computed tomography showed a partially obliterated celiac trunk and an atypical arterial branch that coursed in a retropancreatic plane away from its origin at the superior mesenteric artery to anastomose with the common hepatic artery at the origin of the proper hepatic artery. The gastroduodenal artery and the dorsal pancreatic artery are the 2 conventional anastomotic arcades between the celiac trunk and the superior mesenteric artery. However, another potential anastomotic route is a rare physiological phenomenon known as the arc of Bühler, which, if present, connects the superior mesenteric artery with the celiac trunk or one of its branches. Although the arc of Bühler is known to occur in less than 3% of the general population, it could serve as a crucial anastomotic option in the case of median arcuate ligament syndrome or atheromatous obliteration of the celiac trunk. In our case, we were able to dissect and preserve the entire anastomotic arc from the donor. For arterial reconstruction during liver transplant, we anastomosed the arc of Bühler to the recipient's hepatic artery at the origin of the gastroduodenal artery. The postoperative course was uneventful, and the recipient was in good health at the 6-month follow-up. The arc of Bühler, when present, is an important anastomotic option in hepatobiliary surgery to avoid potential damage to the arterial supply of the liver.

Current Surgical Management of Peri-Hilar and Intra-Hepatic Cholangiocarcinoma.

Cholangiocarcinoma accounts for approximately 10% of all hepatobiliary tumors and represents 3% of all new-diagnosed malignancies worldwide. Intrahepatic cholangiocarcinoma (i-CCA) accounts for 10% of all cases, perihilar (h-CCA) cholangiocarcinoma represents two-thirds of the cases, while distal cholangiocarcinoma accounts for the remaining quarter. Originally described by Klatskin in 1965, h-CCA represents one of the most challenging tumors for hepatobiliary surgeons, mainly because of the anatomical vascular relationships of the biliary confluence at the hepatic hilum. Surgery is the only curative option, with the goal of a radical, margin-negative (R0) tumor resection. Continuous efforts have been made by hepatobiliary surgeons in order to achieve R0 resections, leading to the progressive development of aggressive approaches that include extended hepatectomies, associating liver partition, and portal vein ligation for staged hepatectomy, pre-operative portal vein embolization, and vascular resections. i-CCA is an aggressive biliary cancer that arises from the biliary epithelium proximal to the second-degree bile ducts. The incidence of i-CCA is dramatically increasing worldwide, and surgical resection is the only potentially curative therapy. An aggressive surgical approach, including extended liver resection and vascular reconstruction, and a greater application of systemic therapy and locoregional treatments could lead to an increase in the resection rate and the overall survival in selected i-CCA patients. Improvements achieved over the last two decades and the encouraging results recently reported have led to liver transplantation now being considered an appropriate indication for CCA patients.

A retrospective single-centre analysis of the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in liver transplantation: every nodule matters.

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64-0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48-0.72] when LI-RADS-5 and LI-RADS-TR-V (P = 0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P = 0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54-0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P = 0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance.

Advanced donor age does not increase risk of hepatocellular carcinoma recurrence after liver transplantation: a retrospective two-centre analysis using competing risk analysis.

The impact of donor age on the recurrence of hepatocellular carcinoma (HCC) after liver transplantation is still debated. Between 2002 and 2014, all patients transplanted for HCC in 2 European liver transplantation tertiary centres were retrospectively reviewed. Risk factors for HCC recurrence were assessed using competing risk analysis, and the impact of donor age < or ≥65 years and < or ≥80 years was specifically evaluated after propensity score matching. 728 patients transplanted with a median follow-up of 86 months were analysed. The 1-, 3- and 5-year recurrence rates were 4.9%, 10.7% and 13.9%, respectively. In multivariable analysis, recipient age (sHR: 0.96 [0.93; 0.98], P < 0.01), number of lesions (sHR: 1.05 [1.04; 1.06], P < 0.001), maximum size of the lesions (sHR: 1.37 [1.27; 1.48], P < 0.01), presence of a hepatocholangiocarcinoma (sHR: 6.47 [2.91; 14.38], P < 0.01) and microvascular invasion (sHR: 3.48 [2.42; 5.02], P < 0.01) were significantly associated with HCC recurrence. After propensity score matching, neither donor age ≥65 (P = 0.29) nor donor age ≥80 (P = 0.84) years increased the risk of HCC recurrence. In conclusion, donor age was not found to be a risk factor for HCC recurrence. Patients listed for HCC can receive a graft from an elderly donor without compromising the outcome.