Caratteristiche della popolazione di donatori e riceventi e pratica corrente del matching donatore/ricevente nella coorte dello studio prospettico Liver Match

Le caratteristiche del donatore è una componente cruciale nel processo di allocazione dell'organo che può avere un profondo impatto sul outcome del trapianto. Il numero ridotto di organi disponibili ha portato ad un crescente utilizzo di “extended donors criteria”. Noi abbiamo investigato questa rilevante questione attraverso lo studio Liver Match, nazionale, sponsorizzato dall'associazione AISF-CNT, studio osservazionale condotto da 20 Centri Trapianto di Fegato Italiani per definire l'impatto del matching donatore/ricevente sul outcome post trapianto. Lo studio è stato disegnato per una coorte di 1000 trapianti eseguiti consecutivamente con un follow up minimo di 5 anni. I dati sono raccolti nel data base del Centro Nazionale Trapianti (CNT), che è stato specificatamente implementato per questo progetto. Metodi. Noi abbiamo analizzato 1491 trapianti di organo da cadavere a cuore battente che sono stati donati a riceventi adulti eseguiti dal 01 Giugno 2007 al 31 Maggio 2009. Il data base include le seguenti variabili: dati del donatore, dati del ricevente, dati perioperatori ed operatori e dati di outcome. Expanded criteria donors sono definitidalla presenza di uno o più dei seguenti fattori: età > 60 anni; BMI > 30; steatosi macrovescicolare >30%; sodio sierico >155 mEq/L; tempo d'ischemia fredda > 8 ore; fegato ridotto/split. Resultati. Il 26.5% dei nostri donatori è deceduto per trauma ed il 56.55 per emorragia cerebrale. Come atteso, l'età mediana dei donatori deceduti per trauma cranico è significativamente più bassa se paragonata a quella dei donatori deceduti per cause cerebrovascolari (36 anni vs 60 anni). L'età media della nostra popolazione di 1491 donatori è di 53 anni. I donatori con età >60 anni sono 630 (42.3%) e quelli con età >70 sono 328 (22%). Il valore mediano del BMI è 25. I donatori con BMI tra 25 e 29 sono 580 (39%), con BMI >30 sono 154 (10.3%) e con BMI >35 sono 29 (1.9%). La steatosi macrovescicolare è stata trovata nel 7.5% dei 1058 donatori che ha eseguito la biopsia. Mentre 297 donatori (20.6%) ha un sodio sierico >155 mEq/L. Il valore mediano del tempo d'ischemia fredda è 7.3 ore. I trapianti eseguiti con CIT > 8 ore sono 37% e quelli > 10 ore sono il 9.5%. 79 patienti (5.3%) ha ricevuto un fegato ridotto/split. I donatori HbcAb positivi sono il 16.2% della nostra popolazione. L'età media dei riceventi è 52.7 anni, virtualmente identica a quella dei donatori. Il 77.8% dei riceventi è di sesso maschile. L'epatocarcinoma (HCC) è l'indicazione più frequente nella nostra popolazione di riceventi con una percentuale del 44.5%. Seguono le cirrosi virali (con o senza HCC), che rappresentano il 64.6% di tutte le indicazioni al trapianto, la cirrosi HCV è la causa etiologica più frequente d'indicazione dell'intera casistica, rappresentando il 71 % di tutte le cirrosi virali. La severità clinica di malattia dei riceventi è espressa dal MELD score. Il MELD score ha un valore medio in tutti i trapianti di 16.8 (mediana 15). Il valore del MELD è di 19.9 per tutti i trapianti senza HCC and 13.2 in quelli con HCC. Conclusioni. La proporzione degli extended criteria donors in Italia è estremamente alta, la maggiom parte dei trapianti avviene con organi non standard. Non vi sono delle specifiche politiche di allocazione tra caratteristiche del donatore e severità clinica di malattia del ricevente. Ciò potrebbe avere un importante impatto sul outcome post trapianto.The use of “extended criteria” donors is a challenge to face the shortage of organs for liver transplantation, yet limited data are available in Italy. We investigated this relevant issue within the Liver Match project, a nationwide, AISF- and CNT-sponsored, observational study conducted at 20 Liver Transplantation Centers throughout Italy to assess the impact of donor-recipient matching on transplantation outcomes. The study is designed to enrol 1000 consecutive liver transplants to be followed up for a minimum of 5 years. Data are collected from the National Transplant Center (CNT) data base, which has been specifically implemented for this project. Methods. We analyzed the cross-sectional data of 1491 liver grafts from deceased heart-beating donors transplanted to adult recipients from June 1, 2007 to May 31, 2009. The data base included the following variables: donor data, recipient data, perioperative and operative data and early outcome data. Expanded criteria donors were defined by the presence of one or more of the following: > 60 years; BMI > 30; macrovesicular steatosis >30%; serum sodium >155 mEq/L; cold ischemia time > 8 hours; partial/split liver. Results. Brain death prior to organ procurement was due to a trauma in 26.5% and to cerebral haemorrage in 56.5%. As expected, the median age of donors deceased for traumatic causes was significantly lower compared to donors died because of cerebro-vascular disease (36 vs 60 years). The mean age of the whole population of 1491 donors was 53 years. Donors aged >60 yrs were 630 (42.3%) and those aged >70 were 328 (22%). The median BMI was 25. Donors with BMI between 25 and 29 were 580 (39%), with BMI >30 were 154 (10.3%) and with BMI >35 were 29 (1.9%). Macrovesicular steatosis was found in 7.5% of 1058 biopsied donors. While 297 donors (20.6%) had serum sodium >155 mEq/L. The median cold ischemia time was 7.3 hours. Grafts with a cold ischemia time > 8 hrs were 37% and those with >10 hrs were 9.5%. Sevene-nine patients (5.3%) received a partial/split liver. Serum HbcAb antibodies were present in 16.2% of used donors. The mean age transplant recipient in this cohort was 52.7 years, thus overlapping whit that of donors. Males represented 77.8% of recipient. Presence of hepatocellular carcinoma (HCC) was the most frequent indication for liver transplantation, being present in 44.5 % of the whole recipient population. Among viral-related cirrhosis (with and without HCC), which accounted for 64.6% of the indications to liver transplantation, HCV related cirrhosis was the most frequent etiologic factor, representing 71 % of all viral-related cirrhosis. Recipient clinical severity was assessed measured with the MELD score. The MELD score had a median value at transplant in the whole series of 16.8 (median value =15). The corresponding mean MELD score were 19.9 in patients transplanted without HCC and 13.2 in those transplanted with HCC. Conclusion. The proportion of extended criteria donors in Italy is extremely high, the majority of transplants being performed with non standard livers. No specific allocation policy of extended criteria donors is currently being made in relation to disease severity of adult recipients. These findings may have considerable impact on transplantation outcomes

International comparison of liver transplant programmes:differences in indications, donor and recipient selection and outcome between Italy and UK

Comparing liver transplant (LT) programmes internationally can improve outcomes by stimulating cross-national learning. Yet, comparison of crude outcomes, by using registry data, is limited by missing data, not allowing proper risk-adjustment for donor- and recipient-related factors. The objective of this study was to compare two European LT programmes based on high-quality national longitudinal databases prospectively collected in Italy and UK respectively

Hepatitis B-core Antibody Positive Donors in Liver Transplantation and Their Impact on Graft Survival: Evidence From The Liver Match Cohort Study

BACKGROUND: 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). CONCLUSION: 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 strategie

Cost-effectiveness of pretransplant sofosbuvir for preventing recurrent hepatitis C virus infection after liver transplantation

Abstract There are reports of pretransplant sofosbuvir (SOF) plus ribavirin being effective in preventing recurrent hepatitis C virus (HCV) infection after liver transplantation (LT). The aim of this study was to assess the cost-effectiveness of this strategy in the area served by the North Italy Transplant program. We retrospectively assessed the impact of HCV infection on post-LT survival in 2376 consecutive adult patients (MELD ≤ 25, unknown genotype, period 2004-2009) and the prevalence costs of conventional standard of care (SOC) antiviral therapy (pegylated interferon plus ribavirin) after LT. A Markov model was developed to compare two strategies: 12-24 weeks of SOF+ ribavirin for pre-LT anti-HCV treatment versus on-demand post-LT SOC antiviral therapy. Among the 1794 patients undergoing LT, 860 (48%) were HCV+ and 50% of them were given SOC therapy after LT (mean cost of drugs and adverse effect management = 14,421€ per patient). HCV etiology had a strong impact on post-LT survival (hazard ratio = 1.59, 95% CI = 1.22-2.09, P = 0.0007). After Monte Carlo simulation, pre-LT SOF therapy showed a median survival benefit of 1.5 quality-adjusted life years and an Incremental cost-effectiveness ratio (ICER) of 30,663€/QALY, proving cost-effective in our particular Italian scenario. The costs of SOF therapy, sustained viral response rate 12 weeks after LT, and recipient's age were the main ICER predictors at multivariate analysis. This study proposes a dynamic model based on real-life data from northern Italy for adjusting the costs of pre-LT direct-acting antiviral therapies to the actual sustained virological response reached after LT. © 2015 Steunstichting ESOT. KEYWORDS: cost-effectiveness analysis; hepatitis C virus infection; liver transplantation; recurrent HCV; sofosbuvi

Liver Match, a prospective observational cohort study on liver transplantation in Italy: study design and current practice of donor-recipient matching

The Liver Match is an observational cohort study that prospectively enrolled liver transplantations performed at 20 out of 21 Italian Transplant Centres between June 2007 and May 2009. Aim of the study is to investigate the impact of donor/recipient matching on outcomes. In this report we describe the study methodology and provide a cross-sectional description of donor and recipient characteristics and of graft allocation