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.

Viscoelastic versus conventional coagulation tests to reduce blood product transfusion in patients undergoing liver transplantation: A systematic review and meta-analysis.

BACKGROUND: Recent literature suggests viscoelastic test (VET)-guided transfusion management could be associated with reduced blood product administration in patients undergoing liver transplantation. OBJECTIVES: To assess the effectiveness of coagulation management guided by VETs compared with conventional coagulation tests (CCTs) in reducing blood product transfusion in patients undergoing liver transplantation. DESIGN: Systematic review and meta-analysis of randomised (RCTs) and nonrandomised clinical trials performed according to PRISMA guidelines. The protocol was previously published (PROSPERO: CRD42021230213). DATA SOURCES: The Cochrane Central Library, PubMed/MEDLINE, Embase and the Transfusion Evidence Library were searched up to 30 th January 2022. ELIGIBILITY CRITERIA: Setting: operating room. Patients: liver transplantation recipients. Intervention: use of VETs versus CCTs. Main outcome measures: the primary outcome was the mean number of transfused units for each blood product including red blood cells (RBCs), fresh frozen plasma (FFP), platelets (PLTs) and cryoprecipitate. Secondary outcomes included mortality rate, intensive care unit (ICU) and hospital length of stay (LOS). RESULTS: Seventeen studies ( n  = 5345 patients), 15 observational and two RCTs, were included in this review. There was a mean difference reduction in RBCs [mean difference: -1.40, 95% confidence interval (95% CI), -1.87 to -0.92; P  < 0.001, I2  = 61%) and FFP units (mean difference: -2.98, 95% CI, -4.61 to -1.35; P  =  < 0.001; I2  = 98%) transfused in the VETs group compared with the CCTs one. A greater amount of cryoprecipitate was administered in the VETs group (mean difference: 2.71, 95% CI, 0.84 to 4.58; P  = 0.005; I2  = 91%). There was no significant difference in the mean number of PLT units, mortality, hospital and ICU-LOS. CONCLUSION: Our meta-analysis demonstrated that VETs implementation was associated with reduced RBC and FFP consumption in liver transplantation patients without effects on mortality and hospital and ICU-LOS. The certainty of evidence ranged from moderate to very low. Further well conducted RCTs are needed to improve the certainty of evidence.

Impact of MELD 30-allocation policy on liver transplant outcomes in Italy.

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.

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.

Protective effect of SARS-CoV-2 preventive measures against ESKAPE and Escherichia coli infections.

BACKGROUND/OBJECTIVES: We investigated whether behavioral precautions adopted during Coronavirus disease (COVID-19) pandemic also influenced the spreading and multidrug resistance (MDR) of ESKAPEEc (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii [AB], Pseudomonas aeruginosa, Enterobacter spp and Escherichia Coli, [EC]) among Intensive Care Unit (ICU) patients. SUBJECTS/METHODS: We performed a single-center retrospective study in adult patients admitted to our COVID-19-free surgical ICU. Only patients staying in ICU for more than 48 hours were included. The ESKAPEEc infections recorded during the COVID-19 period (June 1, 2020 - February 28, 2021) and in the corresponding pre-pandemic period (June 1, 2019 - February 28, 2020) were compared. An interrupted time series analysis was performed to rule out possible confounders. RESULTS: Overall, 173 patients in the COVID-19 period and 132 in the pre-COVID-19 period were investigated. The ESKAPEEc infections were documented in 23 (13.3%) and 35 (26.5%) patients in the pandemic and the pre-pandemic periods, respectively (p = 0.005). Demographics, diagnosis, comorbidities, type of surgery, Simplified Acute Physiology Score II, length of mechanical ventilation, hospital and ICU length of stay, ICU death rate, and 28-day hospital mortality were similar in the two groups. In comparison with the pre-pandemic period, no AB was recorded during COVID-19 period, (p = 0.017), while extended-spectrum beta-lactamase-producing EC infections significantly decreased (p = 0.017). Overall, the ESKAPEEc isolates during pandemic less frequently exhibited multidrug-resistant (p = 0.014). CONCLUSIONS: These findings suggest that a robust adherence to hygiene measures together with human contact restrictions in a COVID-19 free ICU might also restrain the transmission of ESKAPEEc pathogens.

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.

Cumulative incidence of solid and hematological De novo malignancy after liver transplantation in a multicentre cohort.

BACKGROUND: Recent innovations in the field of liver transplantation have led to a wealth of new treatment regimes, with potential impact on the onset of de novo malignancies (DNM). The aim of this multicenter cohort study was to provide contemporary figures for the cumulative incidences of solid and hematological DNM after liver transplantation. METHODS: We designed a retrospective cohort study including patients undergoing LT between 2000 and 2015 in three Italian transplant centers. Cumulative incidence was calculated by Kaplan-Meyer analysis. RESULTS: The study included 789 LT patients with a median follow-up of 81 months (IQR: 38-124). The cumulative incidence of non-cutaneous DNM was 6.2% at 5-years, 11.6% at 10-years and 16.3% at 15-years. Post-Transplant Lymphoproliferative Disorders (PTLD) were demonstrated to have a cumulative incidence of 1.0% at 5-years, 1.6% at 10-years and 2.2% at 15-years. Solid Organ Tumors (SOT) demonstrated higher cumulative incidences - 5.3% at 5-years, 10.3% at 10-years and 14.4% at 15-years. The most frequently observed classifications of SOT were lung (rate 1.0% at 5-years, 2.5% at 10-years) and head & neck tumors (rate 1.3% at 5-years, 1.9% at 10-years). CONCLUSIONS: Lung tumors and head & neck tumors are the most frequently observed SOT after LT.

Diagnosis of Acute Rejection of Liver Grafts in Young Children Using Acoustic Radiation Force Impulse Imaging.

OBJECTIVE. Frequency of acute rejection (AR) after pediatric liver transplant remains high despite progress in immunosuppression. Liver biopsy (LB) is the reference standard for the diagnosis of AR despite its potential for morbidity. The purpose of our study was to evaluate the ability of acoustic radiation force impulse (ARFI) imaging to distinguish AR from other causes of short- and medium-term liver dysfunction and to identify liver transplant cases with normal liver function. MATERIALS AND METHODS. ARFI imaging was used to evaluate shear wave velocity (SWV) after liver transplant in young children. All pediatric liver grafts that had LB and ARFI examination between January 2014 and December 2017 were included in this retrospective study. Results of LB were compared with those of SWV. Collected data included age at biopsy and transplant, sex, weight, height, body mass index, interval between liver transplant and shear wave elastography and LB, kind of graft, type of donor, and diagnosis at transplant. ROC curve analysis was performed to assess the diagnostic performance of SWV. Optimal cutoff of SWV using ARFI imaging in predicting AR was identified using the Youden index. RESULTS. Statistical analysis was performed on 54 children; six of the original 60 were excluded because of confounding alterations or changes in outcome. Median SWV was higher in patients with AR (2.03 m/s; interquartile range [IQR], 1.80-2.45 m/s) compared with those with idiopathic hepatitis (1.33 m/s; IQR, 1.12-1.53 m/s), portal hypertension (1.42 m/s; IQR, 1.32-1.72 m/s), cholangitis (1.56 m/s; IQR, 1.07-1.62 m/s) or normal liver function (1.23 m/s; IQR 1.12-1.29 m/s) at protocol biopsies (all comparisons, p < 0.01). SWV higher than 1.73 m/s was predictive for AR (AUC, 0.966). SWV also showed good diagnostic accuracy in normal liver function (AUC, 0.791). ARFI imaging was not predictive for hepatitis (AUC, 0.402), portal hypertension (AUC, 0.556), or cholangitis (AUC, 0.420). CONCLUSION. ARFI imaging could be routinely used in place of LB in pediatric patients with liver dysfunction after liver transplant, restricting indication and risks of biopsy to selected cases.

The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria-In Patients Waiting for Liver Transplantation.

In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC-dependent LT failure, defined as pretransplant tumor-related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IPTW) analysis was used: 1083 MC-in patients (no LRT = 182; LRT = 901) were balanced using 8 variables: age, sex, Model for End-Stage Liver Disease (MELD) value, hepatitis C virus status, hepatitis B virus status, largest lesion diameter, number of nodules, and alpha-fetoprotein (AFP). All the covariates were available at the first referral. After the IPTW, a pseudo-population of 2019 patients listed for LT was analyzed, comparing 2 homogeneous groups of untreated (n = 1077) and LRT-treated (n = 942) patients. Tumor progression after LRT was the most important independent risk factor for HCC-dependent failure (subhazard ratio [SHR], 5.62; P < 0.001). Other independent risk factors were major tumor diameter, AFP, MELD, patient age, male sex, and period of wait-list registration. One single LRT was protective compared with no treatment (SHR, 0.51; P < 0.001). The positive effect was still observed when 2-3 treatments were performed (SHR, 0.66; P = 0.02), but it was lost in the case of ≥4 LRTs (SHR, 0.80; P = 0.27). In conclusion, for MC-in patients, up to 3 LRTs are beneficial for success in intention-to-treat LT patients, with a 49% to 34% reduction in failure risk compared with untreated patients. This benefit is lost if more LRTs are required. A poor response to LRT is associated with a higher risk for HCC-dependent transplant failure.

Intention-to-treat survival benefit of liver transplantation in patients with hepatocellular cancer.

The debate about the best approach to select patients with hepatocellular cancer (HCC) waiting for liver transplantation (LT) is still ongoing. This study aims to identify the best variables allowing to discriminate between "high-" and "low-benefit" patients. To do so, the concept of intention-to-treat (ITT) survival benefit of LT has been created. Data of 2,103 adult HCC patients consecutively enlisted during the period 1987-2015 were analyzed. Three rigorous statistical steps were used in order to create the ITT survival benefit of LT: the development of an ITT LT and a non-LT survival model, and the individual prediction of the ITT survival benefit of LT defined as the difference between the median ITT survival with (based on the first model) and without LT (based on the second model) calculated for each enrolled patient. Four variables (Model for End-Stage Liver Disease, alpha-fetoprotein, Milan-Criteria status, and radiological response) displayed a high effect in terms of delta benefit. According to these risk factors, four benefit groups were identified. Patients with three to four factors ("no-benefit group"; n = 405 of 2,103; 19.2%) had no benefit of LT compared to alternative treatments. Conversely, patients without any risk factor ("large-benefit group"; n = 108; 5.1%) yielded the highest benefit from LT reaching 60 months. CONCLUSION: The ITT transplant survival benefit presented here allows physicians to better select HCC patients waiting for LT. The obtained stratification may lead to an improved and more equitable method of organ allocation. Patients without benefit should be de-listed, whereas patients with large benefit ratio should be prioritized for LT. (Hepatology 2017;66:1910-1919).

Safety of long-term biologic therapy in rheumatologic patients with a previously resolved hepatitis B viral infection.

UNLABELLED: European and Asian studies report conflicting data on the risk of hepatitis B virus (HBV) reactivation in rheumatologic patients with a previously resolved HBV (prHBV) infection undergoing long-term biologic therapies. In this patient category, the safety of different immunosuppressive biologic therapies, including rituximab, was assessed. A total of 1218 Caucasian rheumatologic patients, admitted consecutively as outpatients between 2001 and 2012 and taking biologic therapies, underwent evaluation of anti-HCV and HBV markers as well as liver amino transferases every 3 months. Starting from January 2009, HBV DNA monitoring was performed in patients with a prHBV infection who had started immunosuppressive biologic therapy both before and after 2009. Patients were considered to have elevated aminotransferase levels if values were >1× upper normal limit at least once during follow-up. We found 179 patients with a prHBV infection (14 treated with rituximab, 146 with anti-tumor necrosis factor-alpha, and 19 with other biologic therapies) and 959 patients without a prHBV infection or other liver disease (controls). The mean age in the former group was significantly higher than the controls. Patients with a prHBV infection never showed detectable HBV DNA serum levels or antibody to hepatitis B surface antigen/hepatitis B surface antigen seroreversion. However, when the prevalence of elevated amino transferases in patients with prHBV infection was compared to controls, it was significantly higher in the former group only for aminotransferase levels >1× upper normal limit but not when aminotransferase levels >2× upper normal limit were considered. CONCLUSION: Among patients with a prHBV infection and rheumatologic indications for long-term biologic therapies, HBV reactivation was not seen; this suggests that universal prophylaxis is not justified and is not cost-effective in this clinical setting.

Blood Purification in Hepatic Dysfunction after Liver Transplant or Extensive Hepatectomy: Far from the Best-Case Scenarios.

Background: Hepatic dysfunction (HD) after liver transplantation (LT) or extended hepatic resection (EHR) is associated with graft failure and high short-term mortality. We evaluated the safety and depurative efficacy of CytoSorb® in these settings. The primary endpoint was the change in serum total bilirubin at the end of the treatment compared to the baseline value. The secondary endpoint was to evaluate the trend of serum total bilirubin and coagulation parameters up to 72 h after discontinuation of CytoSorb®. The effects of CytoSorb® therapy on the degree of hepatic encephalopathy (HE), Sequential Organ Failure Assessment (SOFA), and Model for End-Stage Liver Disease (MELD) scores as well as the hemodynamic status compared to baseline were also assessed. Methods: Adult patients with a serum total bilirubin level > 10 mg/dL admitted to the Intensive Care Unit were included. Exclusion criteria were hemodynamic instability, postoperative bleeding and platelet count < 20,000/mm3. Results: Seven patients were treated. Serum total bilirubin was significantly reduced at the end of treatment. However, seventy-two hours after the discontinuation of extracorporeal therapy, bilirubin levels returned to baseline levels in four patients. A decrease in platelet count was found during therapy, and platelet transfusion was required in six cases. A significant increase in D-dimer at the end of treatment was detected. HE degree, SOFA and MELD scores remained stable, while a deterioration in hemodynamic status was observed in two cases. Conclusions: Our preliminary findings did not show the possible benefits of CytoSorb® in rebalancing clinical and laboratory parameters in patients with HD after LT or EHR.

The CUSA Clarity Soft Tissue Removal Study: Clinical Performance Investigation of the CUSA Clarity Ultrasonic Surgical Aspirator System for Soft Tissue Removal During Liver Surgery.

Background: Intraoperative blood loss has an unfavorable impact on the outcome of patients undergoing liver surgery. Today, the use of devices capable of minimizing this risk with high technical performance becomes mandatory. Into this scenario fits the CUSA® Clarity Ultrasonic Surgical Aspirator System. This prospective survey involving five liver surgery centers had the objective of investigating whether this innovative ultrasonic surgical aspirator is safe and effective in the transection of the liver parenchyma. Materials and Methods: This clinical study was a prospective, multicenter, single-arm Post-Market Clinical Follow-up study investigating 100 subjects who underwent liver surgery using the CUSA Clarity Ultrasonic Surgical Aspirator System at five centers during a period of 1 year and 8 months. After collecting all the patient's clinical information and instrument usage details, surgeons completed a brief survey giving their opinions on the performance of CUSA. Therefore, safety and efficacy outcomes were evaluated. Results: Surgeons had a 95% success rate in complete removal of the mass with an average overall operative time of 4 hours and 34 minutes. Overall, there were no complications or device deficiencies. Conclusion: The CUSA Clarity Ultrasonic Surgical Aspirator System performs well during liver surgery with a low complication rate. ClinicalTrials.gov Identifier: NCT04298268.

Immunosuppression in liver transplant oncology: position paper of the Italian Board of Experts in Liver Transplantation (I-BELT).

Liver transplant oncology (TO) represents an area of increasing clinical and scientific interest including a heterogeneous group of clinical-pathological settings. Immunosuppressive management after LT is a key factor relevantly impacting result. However, disease-related guidance is still lacking, and many open questions remain in the field. Based on such a substantial lack of solid evidences, the Italian Board of Experts in Liver Transplantation (I-BELT) (a working group including representatives of all national transplant centers), unprecedently promoted a methodologically sound consensus conference on the topic, based on the GRADE approach. The group final recommendations are herein presented and commented. The 18 PICOs and Statements and their levels of evidence and grades of recommendation are reported and grouped into seven areas: (1) risk stratification by histopathological and bio-molecular parameters and role of mTORi post-LT; (2) steroids and HCC recurrence; (3) management of immunosuppression when HCC recurs after LT; (4) mTORi monotherapy; (5) machine perfusion and HCC recurrence after LT; (6) physiopathology of tumor-infiltrating lymphocytes and immunosuppression, the role of inflammation; (7) immunotherapy in liver transplanted patients. The interest in mammalian targets of rapamycin inhibitors (mTORi), for steroid avoidance and the need for a reduction to CNI exposure emerged from the consensus process. A selected list of unmet needs prompting further investigations have also been developed. The so far heterogeneous and granular approach to immunosuppression in oncologic patients deserves greater efforts for a more standardized therapeutic response to the different clinical scenarios. This consensus process makes a first unprecedented step in this direction, to be developed on a larger scale.

Hepatitis B-core antibody positive donors in liver transplantation and their impact on graft survival: evidence from the Liver Match cohort study.

BACKGROUND & AIMS: The appropriate allocation of grafts from HBcAb positive donors in liver transplantation is crucial, yet a consensus is still lacking. METHODS: We evaluated this issue within Liver Match, a prospective observational Italian study. Data from 1437 consecutive, first transplants performed in 2007-2009 using grafts from deceased heart beating donors were analyzed (median follow-up: 1040 days). Of these, 219 (15.2%) were HBcAb positive. Sixty-six HBcAb positive grafts were allocated to HBsAg positive and 153 to HBsAg negative recipients. RESULTS: 329 graft losses occurred (22.9%): 66 (30.1%) among 219 recipients of HBcAb positive grafts, and 263 (21.6%) among 1218 recipients of HBcAb negative grafts. Graft survival was lower in recipients of HBcAb positive compared to HBcAb negative donors, with unadjusted 3-year graft survival of 0.69 (s.e. 0.032) and 0.77 (0.013), respectively (log-rank, p=0.0047). After stratifying for recipient HBsAg status, this difference was only observed among HBsAg negative recipients (log rank, p=0.0007), 3-year graft survival being excellent (0.88, s.e. 0.020) among HBsAg positive recipients, regardless of the HBcAb donor status (log rank, p=0.4478). Graft loss due to de novo HBV hepatitis occurred only in one patient. At Cox regression, hazard ratios for graft loss were: MELD (1.30 per 10 units, p=0.0002), donor HBcAb positivity (1.56, p=0.0015), recipient HBsAg positivity (0.43, p <0.0001), portal vein thrombosis (1.99, p=0.0156), and DRI (1.41 per unit, p=0.0325). CONCLUSIONS: HBcAb positive donor grafts have better outcomes when transplanted into HBsAg positive than HBsAg negative recipients. These findings suggest that donor HBcAb positivity requires more stringent allocation strategies.

Alpha-fetoprotein and modified response evaluation criteria in solid tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation.

Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collaborating European centers was used for the study. Sixty-one patients (14.5%) developed HCC recurrence. For both MC-IN and MC-OUT patients, an AFP slope > 15 ng/mL/month and mRECIST progression were unique independent risk factors for HCC recurrence and patient death. When the radiological Milan criteria (MC) status was combined with radiological and biological progression, MC-IN and MC-OUT patients without risk factors had similarly excellent 5-year tumor-free and patient survival rates. MC-IN patients with at least 1 risk factor had worse outcomes, and MC-OUT patients with at least 1 risk factor had the poorest survival (P < 0.001). In conclusion, both radiological and biological modifications permit documentation of the response to LRT in patients waiting for LT. According to these 2 parameters, tumor progression significantly increases the risk of recurrence and patient death not only for MC-OUT patients but also for MC-IN patients. The monitoring of both parameters in combination with the initial radiological MC status is an essential element for further refining the selection criteria for potential liver recipients with HCC.