List For Liver Transplantation Research Articles

THU242 - Sarcopenia HIBA score predicts the presence of sarcopenia and mortality in patients on the waiting list for liver transplant

THU242 - Sarcopenia HIBA score predicts the presence of sarcopenia and mortality in patients on the waiting list for liver transplant

Plasma Small Extracellular Vesicles Derived miR-21-5p and miR-92a-3p as Potential Biomarkers for Hepatocellular Carcinoma Screening.

IntroductionLiquid biopsy using circulating microvesicles and exosomes is emerging as a new diagnostic tool that could improve hepatocellular carcinoma (HCC) early diagnosis and screening protocols. Our study aimed to investigate the utility of plasma exosomal miR-21-5p and miR-92-3p for HCC diagnosis during screening protocols.MethodsThe study group included 106 subjects: 48 patients diagnosed with HCC during screening, who underwent a potentially curative treatment (surgical resection or liver transplantation), 38 patients with liver cirrhosis (LC) on the waiting list for liver transplantation, and 20 healthy volunteers. The exosomes were isolated by precipitation with a reagent based on polyethylene glycol and were characterized based on morphological aspects (i.e., diameter); molecular weight; CD63, CD9, and CD81 protein markers; and exosomal miR-21-5p and miR-92a-3p expression levels.ResultsWe first demonstrate that the exosome population isolated with the commercially available Total Exosome Isolation kit respects the same size ranging, morphological, and protein expression aspects compared to the traditional ultracentrifugation technique. The analysis of the expression profile indicates that miR-21-5p was upregulated (p = 0.017), and miR-92a-3p was downregulated (p = 0.0005) in plasma-derived exosomes from HCC subjects, independently from the patient’s characteristics. AUROC for HCC diagnosis based on AFP (alpha-fetoprotein) was 0.72. By integrating AFP and the relative expression of exosomal miR-21-5p and miR-92a-3p in a logistic regression equation for HCC diagnosis, the combined AUROC of the new exosomal miR HCC score was 0.85—significantly better than serum AFP alone (p = 0.0007).ConclusionTogether with serum AFP, plasma exosomal miR-21-5p and miR-92a-3p could be used as potential biomarkers for HCC diagnosis in patients with LC subjected to screening and surveillance.

Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable

BackgroundIn 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA). AimTo analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat. MethodsObservational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found. ResultsBetween 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years. ConclusionThe suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.

First simultaneous and synchronized split-liver transplantation involving two recipients and three surgeons in Costa Rica: A case report

BackgroundCosta Rica has a public health system based on social security, and its transplant program has limited resources. Therefore, when a whole liver is surgically split for transplantation, only one of the obtained grafts can be transplanted. In Costa Rica, there are only three surgeons with expertise and surgical training in liver transplantation with living-donor and split-liver transplantation (SLT) for both pediatric and adult patients. To overcome the existing limitations and the low organ donation rate, a strategy designed to maximize the use of split grafts for liver transplantation was created. This strategy involves the performance of two simultaneous and synchronized SLTs in parallel at two different hospitals. MethodsThis strategy was performed for the first time in May 2018. Simultaneously and synchronously, two SLTs were performed for a woman and a female infant; both patients underwent operations at the same time by only three transplant surgeons in two different hospitals. ResultsThis strategy allowed the performance of two SLTs without compromising the cold ischemia time (CIT) or reperfusion. The infant and woman had a CIT time of 4.5 and 6.0 h, respectively. At 16 months postoperatively, both patients had excellent quality of life and graft function. ConclusionThis first experience with the herein-described surgical and logistical strategy, although successful, requires institutional and governmental support so that the outcomes can be improved to maximize the benefit and opportunity of access for patients on the waiting list for liver transplantation in health systems of third-world countries with limited resources.

Intraoperative Challenge for Vascular Reconstruction in Orthotopic Liver Transplantation Because of Extensive Portal Thrombosis and Intimal Dissection of the Hepatic Artery.

CASE REPORT The presence of the portal vein (PV) thrombosis in cirrhotic patients is not considered an absolute contraindication for liver transplantation, despite being technically challenging and associated with longer operative time and poor outcomes.1 We aim to present a patient with an extensive portal thrombosis who underwent a deceased donor liver transplantation. A 41-year-old man presented with a diagnosis of alcoholic cirrhosis (Model for End-Stage Liver Disease score = 28) and a history of multiple upper gastrointestinal bleeding and refractory ascites. Computed tomography revealed revascularized PV cavernous transformation with signs of left segmental portal hypertension in the splenic, gastric, and esophagic territories, without low-pressure signs in the superior mesenteric vein system (Figure 1). The patient underwent a successful nonanatomical liver transplantation with an implantation of the donor PV into the recipient's left gastric vein (LGV) in an end-to-side fashion. To increase the flow in the liver graft, a distal ligation of LGV was performed to avoid vascular steal phenomenon toward the esophagus or gastric territories (Figure 2). Intraoperatively, a complete intimal dissection of the recipient common hepatic artery was confirmed and thus, the donor hepatic artery flow was reconstructed using an iliac artery interposition graft from the infrarenal aorta (Figure 3). The postoperative outcome was uneventful, and the patient was discharged under anticoagulation therapy on the seventh postoperative day (Video 1; watch the video at https://links.lww.com/ACGCR/A20).Figure 1.: Computed tomography showing signs of segmental portal hypertension in the splenic, gastric, and esophagic areas due to portal vein cavernous transformation.Figure 2.: Nonanatomical reconstruction of the graft portal flow with an implantation of the donor PV into the recipient left gastric vein (distal ligation to increase PV flow). PV, portal vein.Figure 3.: The final aspect of the liver graft vascular reconstruction. The arterial anastomosis of the donor common hepatic artery and iliac artery interposition graft from the infrarenal aorta. PV reconstruction of the donor PV and the recipient left gastric vein. PV, portal vein.The presence of PV thrombosis is a complex scenario in patients on a waiting list for liver transplantation, and it is observed in 10% of preoperative imaging in cirrhotic patients.2 The cause of the occurrence of PV thrombosis is multifactorial, and it is probably related to the presence of extensive fibrosis of the hepatic parenchyma, a procoagulant state, and periportal lymphangitis. Other risk factors have been described including male sex, alcoholic liver disease, previous splenectomy, and the coexistence of a hepatocellular carcinoma. Unfortunately, the presence of PV thrombosis has been associated with poor patient survival after a liver transplantation.3,4 Despite being a challenging situation, it does not represent a contraindication for liver transplantation.1 There are several options to manage portal reconstruction including anatomical reconstruction with portal-portal anastomosis after portal thrombectomy or nonanatomical reconstruction including the implantation of the donor PV in the recipient superior mesenteric vein, LGV, vena cava with or without the use of interposition iliac vein grafts.5 From the surgical point of view, PV flow reconstruction in this setting represents a technical challenge and usually increases operative time, bleeding risk, graft failure rate, and finally, the risk of postoperative PV rethrombosis.6 In our case, it was performed for a nonanatomic PV reconstruction using the recipient LGV with an end-to-lateral anastomosis and distal ligation of the LGV to redirect the portal flow to the liver graft. DISCLOSURES Author contributions: F. Laxague wrote the manuscript and is the article guarantor. V. Agustin provided the video. R. Dario and Q. Emilio edited the manuscript. C. M. Agustina provided the video and images. L. McCormack wrote and revised the manuscript for intellectual content. Financial disclosure: None to report. Informed consent was obtained for this case report.

SUN-685 Approach to a Potential Liver Transplant Candidate with Insulin Antibody-Mediated Severe Insulin Resistance

Introduction: Insulin antibody (IA)-mediated insulin resistance is a rare autoimmune condition resulting in uncontrolled hyperglycemia. High titers of IA are associated with increased mortality secondary to severe insulin resistance and labile blood sugars. There is a paucity of standardized treatment for these patients. Although there have been reported cases of success with immunosuppressants, none of these cases involved patients with liver cirrhosis. We present a case of IA-mediated severe insulin resistance which resulted in uncontrolled hyperglycemia and ultimately delayed liver transplantation. Clinical Case: A 61-year-old male with IA-positive type 2 diabetes, decompensated hepatitis B and NASH cirrhosis presented with several episodes of diabetic ketoacidosis (DKA) and worsening insulin resistance. His liver transplant listing had been placed on hold until glycemic control is achieved. The patient was diagnosed with type 2 diabetes mellitus in 1998. He has no prior autoimmune history. His disease was controlled on Levemir 100 units daily until March 2019 when he presented with his first episode of DKA. He subsequently required 200 units of insulin degludec daily and U-500 insulin 200 units with meals. The patient was readmitted to our hospital in August 2019 for a variceal bleed. His hospital course was complicated by a second occurrence of DKA requiring 100-150 units/hour on an insulin drip for resolution. Labs were significant for HbA1c 8.7% and IA >625 uU/mL (negative if <5.0 uU/mL). He required increasing amounts of basal and prandial insulin after discharge. The patient was again admitted within two months for abdominal pain concerning for spontaneous bacterial peritonitis, which was complicated by his third episode of DKA. Glucoses remained uncontrolled in the range of 170 to 300 mg/dL despite high insulin doses upon discharge. Metformin was contraindicated due to episode of lactic acidosis in the setting of his cirrhosis and concern for repeated episodes of DKA prevented use of SGLT-2 inhibitors. Extensive multidisciplinary discussions led to the decision for an upcoming trial of mycophenolate mofetil followed by plasmapheresis. The goal is to improve glycemic control while also minimizing infection risk to ultimately list him for a liver transplant. Conclusion: This patient highlights a major therapeutic challenge related to uncontrolled hyperglycemia and insulin resistance from anti-insulin antibodies in a cirrhotic patient. This can place patients at high risk for infection, poor wound healing and most importantly prohibit liver transplantation. Immunosuppressant therapy and plasmapheresis may drastically lower insulin antibodies and improve glycemic control, however, it will increase the risk of infection.

Prognostic factors for survival of patients on the liver transplant waiting list

Aim. A single-center prospective cohort study was conducted to identify the factors determining the survival of patients with end-stage liver disease (ESLD) who were on the waiting list for liver transplantation. Material and Methods. A total of 112 patients were examined including 28 individuals who died within six months of followup. The mean score of the model for end-stage liver disease (MELD) was 26.4 ± 3.72 (16–36) among the deceased. Results. Compared to survivors, the deceased patients with end-stage liver diseases had higher incidences of complex heart rhythm disorders. These conditions include runs of supraventricular and ventricular tachycardia, episodes of ventricular trigeminy, a higher number of supraventricular extrasystoles, and the changes in QTc interval duration and QTc interval dispersion. The study showed that compared to the liver transplant recipients that survived, the casualties showed some common characteristics such as lower values of tricuspid valve annular plane systolic excursion; increased values of right heart size, inferior vena cava diameter, peak tricuspid regurgitation velocity, and systolic pressure in the pulmonary artery; decreased ratio of transtricuspid flow velocity in the early diastole to flow velocity in the right atrial systole phase; and higher values of troponin I [0.60 (0.14–1.00) ng/mL vs. 0.24 (0.095–0.465) ng/mL, p = 0.024] and NTproBNP [125.0 (74.0–187.5) pg/mL vs. 82.0 (25.0–125.0) pg/mL, p = 0.011]. Conclusions. Heart rate, troponin I level, and NTproBNP value were identified as additional factors determining the risk of adverse outcomes in liver failure patients on the waiting list for liver transplantation. The study resulted in the development of an informative and efficient mathematical model allowing for assessment of sudden death risk in liver failure patients on the waiting list for liver transplantation.

ANALYSIS OF FOUR-YEAR MANAGEMENT OF PATIENTS WITH VARICOSE BLEEDING IN THE WAITING LIST FOR LIVER TRANSPLANTATION IN ROSTOV REGION

Varicose bleeding is one of the most frequent and severe clinical manifestations of liver cirrhosis. The aim of this study was analyze of the clinical outcome of patients with varicose bleeding in the waiting list for liver transplantation (WL LT). Clinical, laboratory and instrumental data of 134 patients from WL LT were analyzed. Patients were distributed to 4 groups according to clinical outcome in WL LT: delisting, follow-up, death, orthotopic liver transplantation (OLP). Endoscopic ligation was performed in 21 patients (follow-up period from 0 to 33 months in WL LT), TlPs - 7 patients (follow-up period from 2 to 36 months.), azygoportal separation - 18 patients (follow-up period from 4 to 48 months in WL LT). The development of criteria for the priority and timeliness of measures to prevent varicose bleeding is a prerequisite for reducing mortality in the WL LT.

Predisposition Toward Living Liver Donation Is Low Among Relatives of Patients on the Waiting List for Transplantation in Spain

IntroductionThe attitude toward living liver donation (LLD) among the Spanish population is mostly positive; however, the reality is that liver transplants from live donations are currently minimal. Given this situation, studies that analyze these discrepancies should be carried out. ObjectiveAnalyze the attitude toward LLD among family members of patients on the waiting list for liver transplantation. MethodPopulation under study. First-degree relatives of the patients included in the waiting list for liver transplantation. Inclusion criteria. 1. Have the patient's authorization for family members to participate; 2. Accept, the relative, to participate in this investigation; and 3. Be over 18 years old. Opinion survey. The attitude toward LLD is assessed through a questionnaire on psychosocial aspects. ResultsPatients who accepted family members’ participation in the study were 21 of 112, of which 9 placed restrictions on family access, and 12 authorized family members without restrictions. The participants were 1. children: 52.2% (n = 24); 2. brothers: 30.5% (n = 14); and 3. partners: 17.3% (n = 14). Finally, the authorized relatives and participants in the study were 45. Of these, only 44% (n = 20) would accept to be donors. ConclusionsThe access to the LLD of the relatives starts from the restriction and initial rejection of the patients themselves on the waiting list. The promotion of LDD is to initially sensitize patients.

Attitude Toward Related Living Donation Among Patients on Waiting List for Liver Transplantation

IntroductionIn liver transplantation, living donation shows better and better results. However, rates of living liver donation (LLD) are low. ObjectiveTo analyze the attitude towards LLD among patients on the waiting list for liver transplantation. MethodStudy population: Patients included in the waiting list for liver transplantation who are not in code 0 and do not present with encephalopathy above grade I. Protocol: After being included in the waiting list, they are informed of the study and they are cited in the Psychology Consultation. Instruments: attitude questionnaire towards LLD, carried out in the Psychological Care consultation. ResultsOf the 147 patients included in the waiting list, 112 fulfilled the inclusion criteria in the study. After being cited in the consultation, 100% of respondents are in favor of living liver donation. However, when considering the related LLD, 80% of the respondents indicated that they would not accept a living donation from a family member and therefore did not want to complete the questionnaire. Of the remaining 20% who completed the study, 11% would accept it from any family member, 8% only from some family members (mainly excluding children and grandchildren), and the remaining 1% would accept it but excluded all their family members. ConclusionCurrently, there is a disconnect between patients' intentions in favor of living liver donation and the real attitude when they are on the waiting list and related living donation is raised.

Psoas Muscle Index Does Not Predict Post-Transplant Outcomes: A Series of 57 Liver Transplant Recipients

BackgroundSarcopenia is defined as the loss of muscle mass and function. Our aim is to evaluate the degree of sarcopenia by measuring the patients on the waiting list for liver transplantation and its influence on the different post-liver transplant outcomes in our group. MethodsThe psoas muscle index (PMI, cm2/m2) was calculated (right psoas muscle area [cm2]/the square of the body height [m2]) in 57 patients on the waiting list for liver transplantation in our center, and the post-transplant variables relevant to our study were collected. ResultsThe 57 recipients had a mean age of 57 years (range, 35-73) and had a mean of 7.4 months (range, 0-39) on the liver transplant waiting list. The mean psoas muscle index was 2.39 (range, 1-4), and the mean body mass index was 28.01kg/m2 (range, 22-36). After multivariate analysis we found a positive correlation between the PMI and the body mass index of the recipients (r = 0.320, P = .017), intensive care unit length of stay, and donor age (r = 0.319, P = .042), and between cold ischemia time and graft survival (r = 0.366, P = .009). We found no correlation in our sample between PMI and post–liver transplant complications either in terms of graft or patient survival. ConclusionPMI is not representative of total muscle mass and sarcopenia and is not effective in adequately predicting the survival of patients on the waiting list for liver transplantation.

EVALUATION AND SELECTION OF CANDIDATES FOR LIVER TRANSPLANTATION: AN ECONOMIC PERSPECTIVE.

Over the next 20 years, the number of patients on the waiting list for liver transplantation (LTx) is expected to increase by 23%, while pre-LTx costs should raise by 83%. To evaluate direct medical costs of the pre-LTx period from the perspective of a tertiary care center. The study included 104 adult patients wait-listed for deceased donor LTx between October 2012 and May 2016 whose treatment was fully provided at the study transplant center. Clinical and economic data were obtained from electronic medical records and from a hospital management software. Outcomes of interest and costs of patients on the waiting list were compared through the Kruskal-Wallis test. A generalized linear model with logit link function was used for multivariate analysis. P-values <0.05 were considered statistically significant. The costs of patients who underwent LTx ($8,879.83; 95% CI 6,735.24-11,707.27; P<0.001) or who died while waiting ($6,464.73; 95% CI 3,845.75-10,867.28; P=0.04) were higher than those of patients who were excluded from the list for any reason except death ($4,647.78; 95% CI 2,469.35-8,748.04; P=0.254) or those who remained on the waiting list at the end of follow-up. Although protocols of inclusion on the waiting list vary among transplant centers, similar approaches exist and common problems should be addressed. The results of this study may help centers with similar socioeconomic realities adjust their transplant policies.

Late-Onset Hepatic Failure in Children: Risk Factors that Determine the Outcome

Background: Late-onset hepatic failure (LOHF) is a distinct entity of intractable liver diseases with limited pediatric experience. We aimed to identify the etiology and risk factors that determine the poor outcome (PO) of pediatric LOHF. Methods: LOHF was defined as liver failure occurring 5–24 weeks after onset of jaundice and without any evidence of underlying chronic liver disease. PO (death or liver transplantation within 160 days) was compared with spontaneous recovery (SR; complete normalization of liver functions in the native liver). Pediatric end-stage liver disease (PELD) score and King’s College Criteria (KCC) were applied to investigate their prognostic value. Results: We enrolled 47 children (6 [2–16] years) with LOHF. Hepatitis A was the most common etiology (15, 32%) and 64% complicated with infections. Twelve children (25%) had SR over 6 (1–24) months, while 28 (60%) children had PO. Univariate analysis showed indeterminate etiology, hepatic encephalopathy (HE), infection, acute kidney injury, and high PELD score determined PO. On multivariate regression analysis, only PELD score with a cutoff 32 (area under curve 0.833, sensitivity 68%, specificity 92%) predicted PO. KCC showed a sensitivity of 85.7%, specificity of 41.7% to determine PO in our cohort. Conclusion: Indeterminate etiology, presence of HE, occurrence of infection at any site, and acute kidney injury lead to the PO. PELD score ≥32 can be utilized to optimize the listing for liver transplantation. A significant proportion survives with the native liver.

Impact of liver-directed therapy and non-therapy on the waiting time list of patient candidates for liver transplantation: retrospective survival analysis.

Aim of the studyTo determine whether liver-directed therapies (LDT) and no therapy affect waiting list times for liver transplant candidates from a single center.Material and methodsThis retrospective study included patients > 12 years of age diagnosed with hepatocellular carcinoma between January 2014 and June 2019 and followed until the date of transplant, date of delisting, loss to follow-up, or date of death. Waiting list time and associated factors were analyzed using Kaplan-Meier and Cox proportional-hazards methods.ResultsA total of 181 patients met the selection criteria. The mean age was 60 years with standard deviation (SD) of 7.8 years. Sixty-six percent underwent transplant, and 64% were classified within the Milan criteria. Men had a lower median waiting list time than women (191 days vs. 236 days, p = 0.0093). The overall median survival time or time to transplant for 50% of the population was 218 days (95% CI: 195-235). Men displayed a 3.1-fold (95% CI: 1.5-6.2) higher probability of transplantation than women (p = 0.002). Patients who received no therapy had a 5-fold higher probability of undergoing transplantation than patients under arterial LDT (HR [95% CI]: 5 [1.2, 20], p = 0.02). Patients under combined LDT displayed a 70% reduced probability of transplantation compared to patients who received arterial LDTs (p = 0.0009).ConclusionsLDT was associated with a prolonged stay on the transplant list, likely due to the presence of an aggressive liver tumor. However, LDTs allow the patient to remain active on the liver transplant list, increasing their chances of undergoing transplantation.

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study

Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01–11, EudraCT-No. 2012–002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders.

Liver Transplantation Using Right Lobe Graft With Focal Nodular Hyperplasia: Report of 2 Cases

We described 2 cases of adult-to-adult liver transplantation using right lobe grafts donated by 2 patients suffering from focal nodular hyperplasia, the volumes of which were 360 cm3 and 220 cm3. This study was performed in compliance with the Declaration of the Helsinki. For preparation of the graft, back-table hepatic venous outflow reconstruction, including replacement of the retrohepatic inferior vena cava and bridging of hepatic segment V5/V8, was performed by using prosthetic vessel grafts. The liver grafts after subtracting the weight of focal nodular hyperplasia functioned well without serious small-for-size syndrome or graft dysfunction in spite of graft-to-recipient weight ratio less than 0.8%. This suggested the functioning of hepatocyte within focal nodular hyperplasia, which avoided graft deficiency. These 2 recipients were given not only conventional immunosuppressants (tacrolimus and mycophenolate sodium) but also anticoagulants (low molecular weight heparin and warfarin). Thrombosis of the prosthetic inferior vena cava 1 month after transplant in recipient 1 was treated by placement of intravascular stent. Biliary duct anastomotic stricture 2 weeks after transplant in recipient 2 was treated by placement of biliary stent. These 2 recipients remain well at more than 2 years post-transplant. These successful explorative cases highlight the safe use of a graft containing focal nodular hyperplasia. The partial liver resection grafts with focal nodular hyperplasia could be applied to the patients on the waiting list for liver transplantation.

National Experience on Down-Staging of Hepatocellular Carcinoma Before Liver Transplant: Influence of Tumor Burden, Alpha-Fetoprotein, and Wait Time.

United Network for Organ Sharing (UNOS) recently implemented a national policy granting priority listing for liver transplantation (LT) in patients who achieved down-staging of hepatocellular carcinoma (HCC) to Milan criteria. We aimed to evaluate the national experience on down-staging by comparing two down-staging groups with (1) tumor burden meeting UNOS down-staging (UNOS-DS) inclusion criteria and (2) "all-comers" (AC-DS) with initial tumor burden beyond UNOS-DS criteria versus patients always within Milan. This is a retrospective analysis of the UNOS database of 3,819 patients who underwent LT from 2012 to 2015, classified as always within Milan (n=3,276), UNOS-DS (n=422), and AC-DS (n=121). Median time to LT was 12.8months in long wait regions, 6.5months in mid wait regions (MWR), and 2.6months in short wait regions (SWR). On explant, vascular invasion was found in 23.7% of AC-DS versus 16.9% of UNOS-DS and 14.4% of Milan (P=0.002). Kaplan-Meier 3-year post-LT survival was 83.2% for Milan, 79.1% for UNOS-DS (P=0.17 vs. Milan), and 71.4% for AC-DS (P=0.04 vs. Milan). Within down-staging groups, risk of post-LT death in multivariable analysis was increased in SWR or MWR (hazard ratio [HR], 3.1; P=0.005) and with alpha-fetoprotein (AFP)≥100ng/mL at LT (HR, 2.4; P=0.009). The 3-year HCC recurrence probability was 6.9% for Milan, 12.8% for UNOS-DS, and 16.7% for AC-DS (P<0.001). In down-staging groups, AFP≥100 (HR, 2.6; P=0.02) was the only independent predictor of HCC recurrence. Our results validated UNOS-DS criteria based on comparable 3-year survival between UNOS-DS and Milan groups. Additional refinements based on AFP and wait time may further improve post-LT outcomes in down-staging groups, especially given that reported 3-year recurrence was higher than in those always within Milan criteria.

Analysis of four-year management of the waiting list for liver transplantation in Rostov region: prospects for reducing mortality of candidates listed for liver transplantation

Purpose: analysis of various clinical results in patients registered in the liver transplantation waiting list (LTWL).Materials and methods: the study was carried at the Center of Surgery and Donor Coordination of the Rostov Regional Clinical Hospital using clinical, laboratory and instrumental data of 198 patients from the LTWL. 99 men and 99 women were enrolled into this study. The men age ranged from 21 to 70 years (47.8 ± 10.4 years), women age - from 18 to 66 years (49.2 ± 10.9 years). At the time of analysis of the LTWL, the average follow-up period was 14.8 ± 11.2 months. All patients were examined according to the list required for inclusion in the LTWL.Results: depending on the outcome, 198 patients from TLWL were grouped into 4 groups. The first group (delisting group) — 19 patients (9.6 %) with clinical and laboratory indicators that allowed them to be excluded from WL. The second group — 67 patients (33.8 %) who had positive clinical dynamics following therapy. The third group — 39 patients (19.7 %) who underwent liver transplantation. The fourth group — 73 patients (36.9 %) who had negative dynamics following therapy, including patients with a fatal outcome. While keeping LTWL for 4 years, 61 (30.81 %) of 198 listed patients died. The majority (40 patients) died of bleeding from varicose veins and OPPN, 17 patients died of hepatic coma and SPB. Each group represents the distribution of patients according to the MELD-Na scale, the severity of portal hypertension and hepatic encephalopathy.Conclusion: the following factors are indispensable for successful work of the transplant center: systematic work with the territories in order to expand the donor base; defining the patient priority criteria in the LTWL in order to reduce the death rate in the list; detailed examination of the patient before entering the list; forming the observation base; systematic patient observation during the pre- and postoperative period, at the rehabilitation stage, as well as at long-term periods in order to develop an effective algorithm of management of the recipient of a solid organ.

Von Willebrand Factor Facilitates Model of End-Stage Liver Disease-Independent Risk Stratification on the Waiting List for Liver Transplantation

Von Willebrand Factor Facilitates Model of End-Stage Liver Disease-Independent Risk Stratification on the Waiting List for Liver Transplantation

Milan-out Criteria and Worse Intention-to-Treat Outcome Postliver Transplantation.

Background.Milan criteria are widely used for liver transplantation selection in hepatocellular carcinoma but have been recognized to be too restrictive. Milan-out criteria are increasingly being adopted. Our aim was to analyze if liver transplantation waitlisted Milan-out hepatocellular carcinoma patients have different outcome than Milan patients.Methods.Retrospective study including all consecutive patients with hepatocellular carcinoma admitted in the waiting list for liver transplantation between January 2012 and January 2015. We included 177 patients, 146 of which eventually transplanted. Downstaging was achieved in the Milan-out cases (n = 29) before waitlisting.Results.From diagnosis to last follow-up, 29% patients died. Survival at 1 and 5 years from diagnosis was 93% and 75%, respectively in the within Milan group compared with 91% and 61% in the Milan-out group (P = 0.03). Treatment failure occurred in 20% of cases due to tumor progression in the waiting list (44%), death on the waiting list (20%), and hepatocellular carcinoma recurrence postliver transplantation (9%). Milan-out criteria was the only variable predictive of treatment failure remaining in the multivariate analysis with a hazard ratio (HR) of 1.7 (HR, 1.7; 95% confidence interval, 1.34-4.55; P = 0.010) and HR of 1.43 (1.23-6.5) in the hepatocellular carcinoma recurrence.Conclusions.Milan-out criteria are associated with a higher intention-to-treat liver transplantation failure from time of inclusion in the waiting list. However, survival rates are still >50% at 5 years of follow-up.