Recipient hepatectomy technique may affect oncological outcomes of liver transplantation for hepatocellular carcinoma.

To date, caval sparing (CS) and total caval replacement (TCR) for recipient hepatectomy in liver transplantation (LT) have been compared only in terms of surgical morbidity. Nonetheless, the CS technique is inherently associated with an increased manipulation of the native liver and later exclusion of the venous outflow, which may increase the risk of intraoperative shedding of tumor cells when LT is performed for HCC. A multicenter, retrospective study was performed to assess the impact of recipient hepatectomy (CS vs. TCR) on the risk of posttransplant HCC recurrence among 16 European transplant centers that used either TCR or CS recipient hepatectomy as an elective protocol technique. Exclusion criteria comprised cases of non-center-protocol recipient hepatectomy technique, living-donor LT, HCC diagnosis suspected on preoperative imaging but not confirmed at the pathological examination of the explanted liver, HCC in close contact with the IVC, and previous liver resection for HCC. In 2420 patients, CS and TCR approaches were used in 1452 (60%) and 968 (40%) cases, respectively. Group adjustment with inverse probability weighting was performed for high-volume center, recipient age, alcohol abuse, viral hepatitis, Child-Pugh class C, Model for End-Stage Liver Disease score, cold ischemia time, clinical HCC stage within Milan criteria, pre-LT downstaging/bridging therapies, pre-LT alphafetoprotein serum levels, number and size of tumor nodules, microvascular invasion, and complete necrosis of all tumor nodules (matched cohort, TCR, n = 938; CS, n = 935). In a multivariate cause-specific hazard model, CS was associated with a higher risk of HCC recurrence (HR: 1.536, p = 0.007). In conclusion, TCR recipient hepatectomy, compared to the CS approach, may be associated with some protective effect against post-LT tumor recurrence.

Superiority of the new sex-adjusted models to remove the female disadvantage restoring equity in liver transplant allocation.

BACKGROUND AND AIMS: Model for End-stage Liver Disease (MELD) and MELDNa are used worldwide to guide graft allocation in liver transplantation (LT). Evidence exists that females are penalized in the present allocation systems. Recently, new sex-adjusted scores have been proposed with improved performance respect to MELD and MELDNa. GEMA-Na, MELD 3.0, and sex-adjusted MELDNa were developed to improve the 90-day dropout prediction from the list. The present study aimed at evaluating the accuracy and calibration of these scores in an Italian setting. METHODS: The primary outcome of the present study was the dropout from the list up to 90 days because of death or clinical deterioration. We retrospectively analysed data from 855 adults enlisted for liver transplantation in the Lazio region (Italy) (2012-2018). Ninety-day prediction of GEMA-Na, MELD 3.0 and sex-adjusted MELDNa with respect to MELD and MELDNa was analysed. Brier score and Brier Skill score were used for accuracy, and the Greenwood-Nam-D'Agostino test was used to evaluate the calibration of the models. RESULTS: GEMA-Na (concordance = .82, 95% CI = .75-.89), MELD 3.0 (concordance = .81, 95% CI = .74-.87) and sex-adjusted MELDNa (concordance = .81, 95% CI = .74-.88) showed the best 90-day dropout prediction. GEMA-Na showed a higher increase in accuracy with respect to MELD (p = .03). No superiority was shown with respect to MELDNa. All the tested scores showed a good calibration of the models. Using GEMA-Na instead of MELD would potentially save one in nine dropouts and could save one dropout per 285 patients listed. CONCLUSIONS: Validation and reclassification of the sex-adjusted score GEMA-Na confirm its superiority in predicting short-term dropout also in an Italian setting when compared with MELD.

Successful clinical and virological outcomes of liver transplantation for HDV/HBV-related disease after long-term discontinuation of hepatitis B immunoglobulins.

BACKGROUND: Indefinite, long-term administration of hepatitis B immunoglobulins (HBIg), together with a third generation nucleos(t)ide analog (NA), is the currently recommended prophylactic strategy to prevent viral recurrence after liver transplantation (LT) for Hepatitis Delta virus (HDV)/Hepatitis B virus (HBV)-related disease. METHODS: We retrospectively analyzed the safety and long-term clinical and virological outcomes of a consecutive cohort of 16 patients (10 males, median age 64.5, range 41-75) transplanted for HDV/HBV-related cirrhosis at our Institution, who discontinued HBIg after a median of 24.5 months (range 15-116) after transplant. All patients continued prophylaxis with same NA used before LT. Recurrence of HDV/HBV infection was defined as reappearance of serum HDV-RNA with detectable serum HBsAg and/or HBV-DNA. RESULTS: The median follow-up after LT was 138 months (range 73-316) and 110 months (range 52-200) after HBIg withdrawal. All patients were HBsAg-positive, HBV-DNA negative, and anti-HDV positive at the time of LT and without coinfections with HCV or HIV. Patients were followed with biochemical and virological tests every 3-6 months after HBIg withdrawal. No recurrences of HDV/HBV infection or disease were observed during monoprophylaxis with NA. In addition, eight patients (50%) spontaneously developed anti-HBs titers above 10 IU/L at a median of 74 months (range 58-140) following HBIG discontinuation. CONCLUSIONS: HBIg withdrawal after LT is a safe and efficacious strategy in patients transplanted for HDV/HBV disease and is frequently associated with the spontaneous development of serological immunity against HBV. These data call for a revision of current prophylactic recommendations in this setting.

Implementation of Blockchain Technology Could Increase Equity and Transparency in Organ Transplantation: A Narrative Review of an Emergent Tool.

In the last few years, innovative technology and health care digitalization played a major role in all medical fields and a great effort worldwide to manage this large amount of data, in terms of security and digital privacy has been made by different national health systems. Blockchain technology, a peer-to-peer distributed database without centralized authority, initially applied to Bitcoin protocol, soon gained popularity, thanks to its distributed immutable nature in several non-medical fields. Therefore, the aim of the present review (PROSPERO N° CRD42022316661) is to establish a putative future role of blockchain and distribution ledger technology (DLT) in the organ transplantation field and its role to overcome inequalities. Preoperative assessment of the deceased donor, supranational crossover programs with the international waitlist databases, and reduction of black-market donations and counterfeit drugs are some of the possible applications of DLT, thanks to its distributed, efficient, secure, trackable, and immutable nature to reduce inequalities and discrimination.

The impact of center volume on the utilization and outcomes of machine perfusion technology in liver transplantation: An international survey.

INTRODUCTION: Machine perfusion (MP) was developed to expand the donor pool and improve liver transplantation (LT) outcomes. Despite optimal results in clinical trials, the real-world MP benefit in centers with low-/mid-volume activity (LVCs) is still being determined. METHODS: Online survey on MP for LT, distributed to worldwide LT-centers representatives. Variables of interest included logistics, technicalities, and outcomes. Responders were grouped into high-volume centers (HVCs) (>60 LTs/year) and LVCs and results compared. RESULTS: Sixty-seven centers were included, 36 HVCs and 31 LVCs. Significant differences in MP regarded: (I) existence of an established program (80.6% vs. 41.9%; p = 0.02), (II) presence of a dedicated perfusionist (58.3% vs. 22.6%; p = 0.006), (III) duration (>4 h: 47.2% vs. 16.1%; p = 0.01), (IV) routine use (20%-40% vs. 5%-20%; p = 0.002), (V) graft utilization (>50%: 75% vs. 51.6%; p = 0.009), (VI) 90-day patient-survival (90%-100% vs. 50%-90%; p = 0.001) and (VII) subjectively perceived benefit (always vs. only in selected ECD; p = 0.009). Concordance was found for indications, type, viability tests, graft-salvage, 90-day graft-loss, and major-complications. CONCLUSIONS: This study captured a picture of MP in real-world LT-practice. Significant disparities have surfaced between LVCs and HVCs regarding logistics, utilization, and results. To close this gap, efforts should be made to more efficiently deliver dedicated support, training and mentoring to LVC teams adopting MP technology.

Effects of Anti-COVID-19 Vaccination and Pre-Exposure Prophylaxis with Tixagevimab-Cilgavimab in Kidney and Liver Transplant Recipients.

Background and Objectives: Underpowered immune response to vaccines against SARS-CoV-2 was observed in solid organ transplant (SOT) recipients. A novel combination of monoclonal antibodies tixagevimab-cilgavimab (TGM/CGM) received authorization as pre-exposure prophylaxis (PrEP) in those with reduced response to vaccine. We aimed to evaluate the response rate to COVID-19 vaccination in kidney transplant (KT), compared to liver transplant (LT) recipients, and the efficacy and safety of PrEP with TGM/CGM. Material and Methods: Between March and November 2022, adult KT and LT recipients who had completed the vaccination schedule (3 doses) were tested for anti-SARS-CoV-2 antibodies titer. SOT recipients with anti-SARS-CoV-2 titer ≥ 100 IU/mL were considered protected against infection, while those with titer < 100 UI/mL were defined non-protected. Patients with inadequate response were invited to PrEP. Results: In total, 306 patients were enrolled [KT:197 (64.4%), LT:109 (35.6%)]. After the complete scheme of vaccination, 246 (80.3%) patients developed a protective titer, while 60 (19.6%) did not have a protective titer. KT recipients had a lower rate of protective anti-COVID-19 titer compared to LT patients [149 (75.6%) vs. 97 (89.0%), p = 0.004]. Recipients with non-protective anti-COVID-19 titer received mainly tacrolimus-based regimen associated with mycophenolate mofetil (MMF) (70%) e steroids (46.7%) as maintenance immunosuppression, while those treated with everolimus were associated with higher protective titer. Of 35 (58.3%) patients who received PrEP, within 12 months, 6 (17.1%) (all KT) developed pauci-symptomatic COVID-19 disease, while 15/25 (60%) of non-responders, who did not receive the prophylaxis, developed COVID-19 disease. After PrEP, hospitalization rate was lower (2.8% vs. 16%), and no adverse events, neither graft loss nor rejection, were observed. Conclusions: Despite complete COVID-19 vaccination, SOT recipients might be not protected from the SARS-CoV-2 infection, especially after KT. In non-protected SOT patients, the subsequent pre-exposure prophylaxis with combination of monoclonal antibodies (TGM/CGM) might be an efficacy and safe strategy to prevent COVID-19 severe disease and hospitalization.

The impact of cancer on the risk of death with a functioning graft of Italian kidney transplant recipients.

This study assessed the impact of cancer on the risk of death with a functioning graft of kidney transplant (KT) recipients, as compared to corresponding recipients without cancer. A matched cohort study was conducted using data from a cohort of 13 245 individuals who had undergone KT in 17 Italian centers (1997-2017). Cases were defined as subjects diagnosed with any cancer after KT. For each case, two controls matched by gender, age, and year at KT were randomly selected from cohort members who were cancer-free at the time of diagnosis of the index case. Overall, 292 (20.5%) deaths with a functioning graft were recorded among 1425 cases and 238 (8.4%) among 2850 controls. KT recipients with cancer had a greater risk of death with a functioning graft (hazard ratio, HR = 3.31) than their respective controls. This pattern was consistent over a broad range of cancer types, including non-Hodgkin lymphoma (HR = 33.09), lung (HR = 20.51), breast (HR = 8.80), colon-rectum (HR = 3.51), and kidney (HR = 2.38). The survival gap was observed throughout the entire follow-up period, though the effect was more marked within 1 year from cancer diagnosis. These results call for close posttransplant surveillance to detect cancers at earlier stages when treatments are more effective in improving survival.

Electronic Outpatient Referral System for Liver Transplant Improves Appropriateness and Allows First Visit Triage.

BACKGROUND & AIMS: Missed or inappropriate referrals of potential candidates for liver transplantation (LT) are common and traditional referral methods (tRs) do not allow for efficient triage. We investigated the effects of a website developed for electronic outpatient referral to LT (eRW-LT) on these issues. METHODS: We prospectively collected data on all consecutive outpatient referrals to 2 Italian LT centers from January 2015 to December 2019. In the second half of the study, starting from July 2017, referring physicians had the option of using eRW-LT, quickly obtaining the judgment on the appropriateness and urgency of the visit from a transplant hepatologist. RESULTS: In the second half of the study, there were 99 eRW-LTs and 96 traditional referrals (new tRs), representing a 17.4% increase over the 161 traditional referrals (old tRs) of the first half. With eRW-LT, 11.1% of referrals were judged inappropriate online without booking a visit. Appropriateness, judged at the time of the first visit, was 59.6%, 56.2%, and 94.3% with old tRs, new tRs, and eRW-LT, respectively. Considering the appropriate visits, the median waiting time in days between referral date and first visit appointment was significantly shorter for urgent visits referred with eRW-LT (5.0; 95% CI, 4.8-9.3) compared with nonurgent visits sent with the same system (17.0; 95% CI, 11.5-25.0; P < .0001), those referred with old tRs (14.0; 95% CI, 8.0-23.0; P < .001) and with new tRs (16.0; 95% CI, 10.0-23.0; P < .001). CONCLUSIONS: eRW-LT allows an increase in the number of referrals for LT, ensuring effective triage and better appropriateness of visits.

Laparoscopic Left Hemihepatectomy for Intrahepatic Cholangiocellular Carcinoma: An Adequate Lymphadenectomy is Also Possible in Artery Variation.

BACKGROUND: Laparoscopic liver resection (LLR) is becoming essential in the treatment of malignant liver tumors but only a few reports exist about LLR for intrahepatic cholangiocarcinoma (IHCC). METHODS: We present a video of a laparoscopic left hemihepatectomy with lymphadenectomy for IHCC. CASE PRESENTATION: A 67-year-old asymptomatic male underwent a routine abdominal ultrasound, revealing a 15 × 9 mm solid nodular iso-hyperechoic lesion, located in SIII, with SII/III biliary duct dilation. Magnetic resonance imaging confirmed a 32 × 22 mm lesion in SII/III, with mild hyper-intensity on T2-weighted images and strong hypo-intensity on T1-weighted images. After administration of contrast medium, the lesion showed light peripheral enhancement on the portal and delayed phases, and hypo-intensity on the hepatospecific phase. No relevant comorbidities were reported (KPS 100). Laboratory tests showed normal liver function and normal CA19-9 levels. A laparoscopic left hemihepatectomy was indicated. RESULTS: Operative time was 330 min. Four intermittent Pringle maneuver cycles were applied and no blood transfusions were administered. Intraoperative ultrasound confirmed preoperative findings and additionally highlighted involvement of the SIV duct. A full replacing right hepatic artery arising from the superior mesenteric artery was identified and was preserved during hilar dissection. Postoperative course was uneventful and the patient was discharged on postoperative day 3. The pathology report indicated cholangiocellular carcinoma pT1bN0. Twelve lymph nodes were retrieved. CONCLUSIONS: According to recent literature reports and our experience, laparoscopic surgery for intrahepatic cholangiocellular carcinoma should be considered feasible and safe in selected patients. Hepatic artery variations allow for adequate lymphadenectomy. Oncological long-term results require multicenter randomized studies in order to be validated.

Renal Function, Adherence and Quality of Life Improvement After Conversion From Immediate to Prolonged-Release Tacrolimus in Liver Transplantation: Prospective Ten-Year Follow-Up Study.

Immunosuppression non-adherence is a major cause of graft failure after liver transplantation. The aim of this study was to evaluate practice surrounding conversion from immediate-release to prolonged-release Tacrolimus formulation and to assess patient adherence and quality of life (QoL). One hundred and seven adult liver transplant recipients, receiving immediate-release Tacrolimus for a minimum of 6 months, were converted to prolonged-release formulation, based on a dose ratio of one (1:1). The median follow-up was 120 [IQR, 120-123] months. Tacrolimus dosage and blood level, liver and renal function, lipid and glucose profiles were recorded. In addition, questionnaires were submitted to evaluate adherence and QoL following conversion. No rejection was recorded. The median serum Tacrolimus blood level decreased over 1 month (5.80, [IQR, 2.0-10.8] vs. 3.8 [IQR, 1.4-8.7]; p < 0.0005). Significant improvement in renal function was noted (median GFR was 81.7 [IQR, 43.4-128.6] vs. 73.9 [IQR, 27.1-130.2]; p = 0.0002). At the end of the follow-up, conversion resulted in an overall decrease in non-adherence of 53.3% (p = 0.0001) and an improvement in QoL was reported by 76.2% of patients. Thus, 1:1 conversion from immediate to prolonged-release Tacrolimus is safe, feasible and efficient, avoiding under-therapeutic and toxic peak concentrations, improving renal function, adherence to immunosuppression and overall patient QoL.

Prolonged-Release Once-Daily Formulation of Tacrolimus Versus Standard-of-Care Tacrolimus in de novo Kidney Transplant Patients Across Europe.

Background: Tacrolimus is the calcineurin inhibitor of choice for preventing acute rejection episodes in kidney transplant patients. However, tacrolimus has a narrow therapeutic range that requires regular monitoring of blood concentrations to minimize toxicity. A new once-daily tacrolimus formulation, LCP-tacrolimus (LCPT), has been developed, which uses MeltDose™ drug-delivery technology to control drug release and enhance overall bioavailability. Our study compared dosing of LCPT with current standard-of-care tacrolimus [immediate-release tacrolimus (IR-Tac) or prolonged-release tacrolimus (PR-Tac)] during the 6 months following de novo kidney transplantation. Comparisons of graft function, clinical outcomes, safety, and tolerability for LCPT versus IR-Tac/PR-Tac were also performed. Methods: Standard immunological risk patients with end-stage renal disease who had received a de novo kidney transplant were randomized (1:1) to LCPT (N = 200) or IR-Tac/PR-Tac (N = 201). Results: Least squares (LS) mean tacrolimus total daily dose from Week 3 to Month 6 was significantly lower for LCPT than for IR-Tac/PR-Tac. Although LS mean tacrolimus trough levels were significantly higher for LCPT than IR-Tac/PR-Tac, tacrolimus trough levels remained within the standard reference range for most patients. There were no differences between the groups in treatment failure measures or safety profile. Conclusion: LCPT can achieve similar clinical outcomes to other tacrolimus formulations, with a lower daily dose. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT02432833.

Liver transplantation from active COVID-19 donors: Is it ethically justifiable?

The debate on the opportunity to use organs from donors testing positive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in recipients with naïve resolved or active COVID-19 is ongoing. We aim to present the ethical analyses underlying the decision to perform liver transplantation (LT) in selected patients with resolved or active COVID-19 in Italy. We used Jonsen, Siegler, and Winslade's Four-Boxes casuistic method, addressing the four topics considered as constitutive of the essential structure of single clinical cases for their ethical analysis (medical indications, patient preferences, quality of life, and contextual features) to enable decision-making on a case-by-case basis. Based on these topics, we elucidate the meaning and balance among the principles of biomedical ethics. Clinical ethics judgment based on the relation between the risk of acquiring SARS-CoV-2 along with its potentially negative effects and the expected benefits of transplant lead to consider LT as clinically appropriate. Shared decision-making allows the integration of clinical options with the patient's subjective preferences and considerations, enabling a valid informed consent specifically tailored to the patients' individual circumstances. The inclusion of carefully selected SARS-CoV-2 positive donors represents an opportunity to offer lifesaving LT to patients who might otherwise have limited opportunities to receive one. COVID-19 positive donor livers are fairly allocated among equals, and respect for fundamental rights of the individual and the broader community in a context of healthcare rationing is guaranteed.The ethical analysis of the decision to perform LT in selected patients shows that the decision is ethically justifiable.

Technical feasibility and short-term outcomes of laparoscopic isolated caudate lobe resection: an IgoMILS (Italian Group of Minimally Invasive Liver Surgery) registry-based study.

BACKGROUND: Although isolated caudate lobe (CL) liver resection is not a contraindication for minimally invasive liver surgery (MILS), feasibility and safety of the procedure are still poorly investigated. To address this gap, we evaluate data on the Italian prospective maintained database on laparoscopic liver surgery (IgoMILS) and compare outcomes between MILS and open group. METHODS: Perioperative data of patients with malignancies, as colorectal liver metastases (CRLM), hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), non-colorectal liver metastases (NCRLM) and benign liver disease, were retrospectively analyzed. A propensity score matching (PSM) analysis was performed to balance the potential selection bias for MILS and open group. RESULTS: A total of 224 patients were included in the study, 47 and 177 patients underwent MILS and open isolated CL resection, respectively. The overall complication rate was comparable between the two groups; however, severe complication rate (Dindo-Clavien grade ≥ 3) was lower in the MILS group (0% versus 6.8%, P = ns). In-hospital mortality was 0% in both groups and mean hospital stay was significantly shorter in the MILS group (P = 0.01). After selection of 42 MILS and 43 open CL resections by PSM analysis, intraoperative and postoperative outcomes remained similar except for the hospital stay which was not significantly shorter in MILS group. CONCLUSIONS: This multi-institutional cohort study shows that MILS CL resection is feasible and safe. The surgical procedure can be technically demanding compared to open resection, whereas good perioperative outcomes can be achieved in highly selected patients.

Liver transplantation performed in a SARS-CoV-2 positive hospitalized recipient using a SARS-CoV-2 infected donor.

The coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 currently affected more than 108 million people worldwide with a fatality rate of 2.2%. Herein, we report the first case of liver transplantation (LT) performed with a liver procured from a SARS-CoV-2 positive donor. The recipient was a 35-year-old SARS-CoV-2 positive female patient affected by severe end-stage HBV-HDV-related liver disease (model of end-stage liver disease = 32) who had neutralizing SARS-CoV-2 antibodies (titers 1:320) at time of LT. The LT was successful, and the graft is functioning two months after surgery. The recipient cleared the SARS-CoV-2 infection 1 month after LT. The current case shows that the prompt use of SARS-CoV-2 infected liver donors offers an invaluable life-saving opportunity for SARS-CoV-2 positive wait-listed patients who developed neutralizing SARS-CoV-2 antibodies.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

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.

Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.

Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-LT levels of alpha-fetoprotein, Model for End-Stage Liver Disease Sodium score, and tumor burden score was recalibrated among a randomly selected cohort (n = 1,021) and validated in the remainder (n = 3,068). This study demonstrated significant heterogeneity by site and year, reflecting practice trends over the last decade. On explant pathology, both vascular invasion (VI) and poorly differentiated component (PDC) increased with increasing HALTHCC score. The lowest-risk patients (HALTHCC 0-5) had lower rates of VI and PDC than the highest-risk patients (HALTHCC > 35) (VI, 7.7%[ 1.2-14.2] vs. 70.6% [48.3-92.9] and PDC:4.6% [0.1%-9.8%] vs. 47.1% [22.6-71.5]; P < 0.0001 for both). This trend was robust to MC status. This international study was used to adjust the coefficients in the HALTHCC score. Before recalibration, HALTHCC had the greatest discriminatory ability for overall survival (OS; C-index = 0.61) compared to all previously reported scores. Following recalibration, the prognostic utility increased for both recurrence (C-index = 0.71) and OS (C-index = 0.63). Conclusion: This large international trial validated and refined the role for the continuous risk metric, HALTHCC, in establishing pre-LT risk among candidates with HCC worldwide. Prospective trials introducing HALTHCC into clinical practice are warranted.

Sarco-Model: A score to predict the dropout risk in the perspective of organ allocation in patients awaiting liver transplantation.

BACKGROUND & AIMS: Sarcopenia in liver transplantation (LT) cirrhotic candidates has been connected with higher dropouts and graft losses after transplant. The study aims to create an 'urgency' model combining sarcopenia and Model for End-stage Liver Disease Sodium (MELDNa) to predict the risk of dropout and identify an appropriate threshold of post-LT futility. METHODS: A total of 1087 adult cirrhotic patients were listed for a first LT during January 2012 to December 2018. The study population was split into a training (n = 855) and a validation set (n = 232). RESULTS: Using a competing-risk analysis of cause-specific hazards, we created the Sarco-Model2 . According to the model, one extra point of MELDNa was added for each 0.5 cm2 /m2 reduction of total psoas area (TPA) < 6.0 cm2 /m2 . At external validation, the Sarco-Model2 showed the best diagnostic ability for predicting the risk of 3-month dropout in patients with MELDNa < 20 (area under the curve [AUC] = 0.93; P = .003). Using the net reclassification improvement, 14.3% of dropped-out patients were correctly reclassified using the Sarco-Model2 . As for the futility threshold, transplanted patients with TPA < 6.0 cm2 /m2 and MELDNa 35-40 (n = 16/833, 1.9%) had the worse results (6-month graft loss = 25.5%). CONCLUSIONS: In sarcopenic patients with MELDNa < 20, the 'urgency' Sarco-Model2 should be used to prioritize the list, while MELDNa value should be preferred in patients with MELDNa ≥ 20. The Sarco-Model2 played a role in more than 30% of the cases in the investigated allocation scenario. In sarcopenic patients with a MELDNa value of 35-40, 'futile' transplantation should be considered.

Factors influencing diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) in pancreatic and biliary tumors.

BACKGROUND AND AIM: Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is influenced by several factors, primarily operator expertise. Formal training in EUS-FNA, as suggested by the European Society of Gastrointestinal Endoscopy and the American Society for Gastrointestinal Endoscopy guidelines, is not always available and is often expensive and time-consuming. In this study we evaluate factors influencing the diagnostic accuracy of pancreatic EUS-FNA. METHODS: In a retrospective study, 557 consecutive EUS-FNAs were evaluated. Several variables relating to the procedures were considered to calculate the EUS-FNA performance over eight years. RESULTS: A total of 308 out of 557 EUS-FNAs were selected. Overall sensitivity of EUS-FNA was 66% (95% CI: 60.8-71.8), specificity 100%, and diagnostic accuracy 69% (95% CI: 64.0-74.4). An increase in diagnostic accuracy was observed to >90% using a new fine-needle biopsy (FNB) needle and in the case of simultaneous sampling of primary and metastatic lesions. Diagnostic accuracy >80% was observed after 250 procedures, in the absence of rapid on-site cytopathological examination (ROSE). Multivariate logistic regression analysis confirmed that the FNB needle, operator skill, and double EUS-FNA sampling are associated with high diagnostic accuracy. CONCLUSIONS: The learning curve for EUS-FNA may be longer and a considerable number of procedures are needed to achieve high diagnostic accuracy in the absence of ROSE. However, the use of FNB needles and the simultaneous sampling of primary and metastatic lesions can rapidly improve the diagnostic accuracy of the procedure.

Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.

COVID-19, liver transplant, and immunosuppression: Allies or foes?

Liver transplant (LT) recipients are considered at a particularly high risk for developing critical COVID-19 infection. To date, available data are heterogeneous and scarce and mortality in LT recipients seems to be higher compared to normal population, but whether this is caused by altered immunological status, immunosuppression (IS), or underlying comorbidities has not yet been fully clarified. Some evidences show that IS might play a role in the pathophysiology of this new disease. We searched all available data regarding LT recipients infected by COVID-19, focusing on the role of IS. To date, 244 LT recipients have been reported as COVID-19-positive. Trends among transplant physicians are to reduce overall IS, especially antimetabolite drugs, but the current available observations are still not enough to build strong evidences for recommendation and IS should be meticulously tailored case by case.