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.

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.

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.

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.

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.

Prediction of poor graft function by means of gastric tonometry in patients undergoing liver transplantation.

UNLABELLED: INTRODUCTION. Splanchnic hypoperfusion appears to play a key role in the failure of functional recovery of the graft after orthotopic liver transplantation (LT). The aim of this study was to determine if alterations of tonometric parameters, which are related to splanchnic perfusion, could predict poor graft function in patients undergoing LT. MATERIALS AND METHODS: After Ethics Committee approval, 68 patients undergoing LT were enrolled. In all the patients, regional-arterial CO2 gradient (Pr-aCO2) was recorded; in addition, the difference between Pr-aCO2 recorded at anhepatic phase (T1) and at the end of surgery (T2) (T2- T1 = ΔPr-aCO2) was calculated. Poor graft function was determined on the basis of Toronto's classification 72 hours after LT. Student t-test and logistic regression analysis were used for statistical purpose. Results. ΔPr-aCO2 was significantly greater in patients with poor graft function (3.5 ± 13.2) compared to patients with good graft function (-5.8 ± 12.3) (p = 0.014). The logistic regression analysis showed that the ΔPr-aCO2 was able to predict the onset of poor graft function (p = 0.037). A value of ΔPr-aCO2 ≥ -4 was associated with poor graft function with a sensibility of 93.3% and a specificity of 42.3%. CONCLUSION. Our study suggests that the change of Pr-aCO2 may be a valuable index of graft dysfunction. Gastric tonometry might give early prognostic information on the graft outcome, and it may aid clinicians in planning a more strict follow-up and proper interventions in order to improve graft survival.

The liver transplant surgeon Mondays blues: an Italian perspective.

Poor data exist on the influence of holidays and weekdays on the number and the results of liver transplantation (LT) in Italy. The study's main objective is to investigate the impact of holidays and the different days of the week on the LT number and early graft survival rates in a multi-centric Italian series. We performed a retrospective analysis on 1,026 adult patients undergoing first deceased-donor transplantation between January 2004 and December 2018 in the three university centers in Rome. During the 4,504 workdays, 881 LTs were performed (85.9%; one every 5.1 days on average). On the opposite, 145 LTs were done during the 975 holidays (14.1%; one every 7.1 days on average). Fewer LTs were performed on holidays (P = 0.004). There were no substantial differences in donor-, recipient- and transplant-related characteristics in LTs performed on weekdays or holidays. On Monday, fewer transplants were performed (vs. other weekdays: P < 0.0001; vs. Sunday: P = 0.03). At multivariable Cox regression analysis, LTs performed during the holiday or during the different days of the week were not found to be independent risk factors for the risk of 3- and 12-month graft loss. At three-month survival curves, no differences were observed among the transplants performed during the holidays versus the workdays (86.2 vs. 85.0%; P-0.70). The range of graft survival rates based on the day of the week was 81.6-86.9%, without showing any significant differences (P = 0.57). Fewer transplants are performed on holidays and Mondays. Survivals are not affected by holidays or the day the transplant is performed.

The Role of Donor Gamma-Glutamyl Transferase as a Risk Factor for Early Graft Function after Liver Transplantation.

BACKGROUND: Growing interest has been recently reported in the potential detrimental role of donor gamma-glutamyl transferase (GGT) peak at the time of organ procurement regarding the risk of poor outcomes after liver transplantation (LT). However, the literature on this topic is scarce and controversial data exist on the mechanisms justifying such a correlation. This study aims to demonstrate the adverse effect of donor GGT in a large European LT cohort regarding 90-day post-transplant graft loss. METHODS: This is a retrospective international study investigating 1335 adult patients receiving a first LT from January 2004 to September 2018 in four collaborative European centers. RESULTS: Two different multivariable logistic regression models were constructed to evaluate the risk factors for 90-day post-transplant graft loss, introducing donor GGT as a continuous or dichotomous variable. In both models, donor GGT showed an independent role as a predictor of graft loss. In detail, the log-transformed continuous donor GGT value showed an odds ratio of 1.46 (95% CI = 1.03-2.07; p = 0.03). When the donor GGT peak value was dichotomized using a cut-off of 160 IU/L, the odds ratio was 1.90 (95% CI = 1.20-3.02; p = 0.006). When the graft-loss rates were investigated, significantly higher rates were reported in LT cases with donor GGT ≥160 IU/L. In detail, 90-day graft-loss rates were 23.2% vs. 13.9% in patients with high vs. low donor GGT, respectively (log-rank p = 0.004). Donor GGT was also added to scores conventionally used to predict outcomes (i.e., MELD, D-MELD, DRI, and BAR scores). In all cases, when the score was combined with the donor GGT, an improvement in the model accuracy was observed. CONCLUSIONS: Donor GGT could represent a valuable marker for evaluating graft quality at transplantation. Donor GGT should be implemented in scores aimed at predicting post-transplant clinical outcomes. The exact mechanisms correlating GGT and poor LT outcomes should be better clarified and need prospective studies focused on this topic.

Recurrence of hepatocellular cancer after liver transplantation: the role of primary resection and salvage transplantation in East and West.

BACKGROUND & AIMS: Greater tumor aggressiveness and different management modalities of hepatocellular cancer (HCC) before liver transplantation (LT) may explain the higher recurrence rates reported in Asia. This study investigates the prognostic factors for HCC recurrence in a Western and an Eastern HCC patient cohort in order to analyze the respective roles of tumor- and management-related factors on the incidence of post-LT HCC recurrence. METHODS: Data of 273 HCC patients, transplanted during the period January 1999-March 2009, were obtained from the Rome Inter-University Liver Transplant Consortium (n=157) and Hong Kong University (n=116) databases. Median follow-up was 4.3 years (range: 0.2-12). Recurrence rate and multivariate logistic regression analysis was performed on the entire population and on Milan criteria-in (MC-in) patients. RESULTS: Multivariate analysis on the entire population identified four independent risk factors for post-LT HCC recurrence: microvascular invasion (odds ratio, OR=4.88; p=0.001), poor tumor grading (OR=6.86; p=0.002), diameter of the largest tumor (OR=4.72; p=0.05), and previous liver resection (LR) (OR=3.34; p=0.04). After removal of LR, only tumor-related variables were independent risk factors for recurrence. When only MC-in patients were analyzed, no difference was observed between the two cohorts in terms of recurrence rate after LR patient removal. CONCLUSIONS: LR followed by salvage "for HCC recurrence" LT represents the main reason for a higher HCC recurrence rate in the Hong Kong patients, but not LR followed by salvage "for liver failure" LT in the Roman group. This approach towards HCC before LT may not be universally applicable. The precise patient background must be taken into account in order to identify the best pre-LT strategy.

Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation.

BACKGROUND: In the last several years, there has been no agreement on how to possibly expand the Milan criteria (MC) in the selection of patients with hepatocellular carcinoma (HCC) for listing for liver transplant (LT). The aim of the study is to evaluate morphological and biological tumor parameters to identify new expanded criteria for the selection of patients with HCC as candidates for LT. METHODS: We retrospectively analyzed 158 consecutive patients with HCC who underwent LT. RESULTS: Twelve (7.6%) recurrences were observed. At multivariate analysis, alpha-fetoprotein (AFP) >400 ng/mL (odds ratio [OR] 8.4, p<0.01) and total tumor diameter (TTD) >8 cm (OR 7.4, p=0.01) were the strongest predictors for recurrence. AFP-TTD criteria resulted in a low five-yr recurrence rate (4.9%) and an increased number of LT compared with the MC (22.2% increase). The five-yr disease-free survival rate was 74.4% in AFP-TTD criteria in patients, with a higher effectiveness in stratifying the cohort with respect to the MC. CONCLUSIONS: Both AFP and TTD are good independent predictors of HCC recurrence. Their combination appears to obtain a better selection of candidates for LT without worsening patient survival and recurrence rates. This approach allows for an increase in the number of potentially transplantable patients.

http://www.D-MELD.com, the Italian survival calculator to optimize donor to recipient matching and to identify the unsustainable matches in liver transplantation.

Optimization of donor-recipient match is one of the exciting challenges in liver transplantation. Using algorithms obtained by the Italian D-MELD study (5256 liver transplants, 21 Centers, 2002-2009 period), a web-based survival calculator was developed. The calculator is available online at the URL http://www.D-MELD.com. The access is free. Registration and authentication are required. The website was developed using PHP scripting language on HTML platform and it is hosted by the web provider Aruba.it. For a given donor (expressed by donor age) and for three potential recipients (expressed by values of bilirubin, creatinine, INR, and by recipient age, HCV, HBV, portal thrombosis, re-transplant status), the website calculates the patient survival at 90days, 1year, 3years, and allows the identification of possible unsustainable matches (i.e. donor-recipient matches with predicted patient survival less than 50% at 5 years). This innovative approach allows the selection of the best recipient for each referred donor, avoiding the allocation of a high-risk graft to a high-risk recipient. The use of the D-MELD.com website can help transplant surgeons, hepatologists, and transplant coordinators in everyday practice of matching donors and recipients, by selecting the more appropriate recipient among various candidates with different prognostic factors.

Proposal and validation of a liver graft discard score for liver transplantation from deceased donors: a multicenter Italian study.

Several studies have explored the risk of graft dysfunction after liver transplantation (LT) in recent years. Conversely, risk factors for graft discard before or at procurement have poorly been investigated. The study aimed at identifying a score to predict the risk of liver-related graft discard before transplantation. Secondary aims were to test the score for prediction of biopsy-related negative features and post-LT early graft loss. A total of 4207 donors evaluated during the period January 2004-Decemeber 2018 were retrospectively analyzed. The group was split into a training set (n = 3,156; 75.0%) and a validation set (n = 1,051; 25.0%). The Donor Rejected Organ Pre-transplantation (DROP) Score was proposed: - 2.68 + (2.14 if Regional Share) + (0.03*age) + (0.04*weight)-(0.03*height) + (0.29 if diabetes) + (1.65 if anti-HCV-positive) + (0.27 if HBV core) - (0.69 if hypotension) + (0.09*creatinine) + (0.38*log10AST) + (0.34*log10ALT) + (0.06*total bilirubin). At validation, the DROP Score showed the best AUCs for the prediction of liver-related graft discard (0.82; p < 0.001) and macrovesicular steatosis ≥ 30% (0.71; p < 0.001). Patients exceeding the DROP 90th centile had the worse post-LT results (3-month graft loss: 82.8%; log-rank P = 0.024).The DROP score represents a valuable tool to predict the risk of liver function-related graft discard, steatosis, and early post-LT graft survival rates. Studies focused on the validation of this score in other geographical settings are required.

Thromboelastography does not reduce transfusion requirements in liver transplantation: A propensity score-matched study.

STUDY OBJECTIVE: To compare total blood product requirements in liver transplantation (LT) assisted by thromboelastography (TEG) or conventional coagulation tests (CCTs). DESIGN: Retrospective observational study. SETTING: A tertiary care referral center for LT. PATIENTS: Adult patients undergoing LT from deceased donor. INTERVENTION: Hemostasis was monitored by TEG or CCTs and corresponding transfusion algorithms were adopted. MEASUREMENTS: Number and types of blood products (red blood cells, RBC; fresh-frozen plasma, FFP; platelets, PLT) transfused from the beginning of surgery until the admission to the intensive care unit. METHODS: We compared data retrospectively collected in 226 LTs, grouped according to the type of hemostasis monitoring (90 with TEG and 136 with CCTs, respectively). Confounding variables affecting transfusion needs (recipient age, sex, previous hepatocellular carcinoma surgery, Model for End Stage Liver Disease - MELD, baseline hemoglobin, fibrinogen, creatinine, veno-venous by pass, and trans-jugular intrahepatic portosystemic shunt) were managed by propensity score match (PSM). MAIN RESULTS: The preliminary analysis showed that patients in the TEG group received fewer total blood products (RBC + FFP + PLT; p = 0.001, FFP (p = 0.001), and RBC (p = 0.001). After PSM, 89 CCT patients were selected and matched to the 90 TEG patients. CCT and TEG matched patients received similar amount of total blood products. In a subgroup of 39 patients in the top MELD quartile (MELD ≥25), the TEG use resulted in lower consumption of FFP units and total blood products. Nevertheless, due to the low number of patients, any meaningful conclusion could be achieved in this subgroup. CONCLUSIONS: In our experience, TEG-guided transfusion in LT does not reduce the intraoperative blood product consumption. Further studies are warranted to assess an advantage for TEG in either the entire LT population or the high-MELD subgroup of patients.