Delisting of liver transplant candidates with chronic hepatitis C after viral eradication: A European study

被引:254
作者
Belli, Luca Saverio [1 ]
Berenguer, Marina [2 ]
Cortesi, Paolo Angelo [3 ]
Strazzabosco, Mario [4 ,5 ,6 ]
Rockenschaub, Susanne-Rasoul [7 ]
Martini, Silvia [8 ]
Morelli, Cristina [9 ]
Donato, Francesca [10 ]
Volpes, Riccardo [11 ]
Pageaux, Georges-Philippe [12 ]
Coilly, Audrey [13 ]
Fagiuoli, Stefano [14 ]
Amaddeo, Giuliana [15 ,16 ]
Perricone, Giovanni [1 ]
Vinaixa, Carmen [2 ]
Berlakovich, Gabriela [7 ]
Facchetti, Rita [3 ]
Polak, Wojciech [17 ]
Muiesan, Paolo [18 ]
Duvoux, Christophe [15 ,16 ]
机构
[1] Osped Niguarda Ca Granda, Liver Unit, Dept Gastroenterol & Hepatol, Piazza Osped Maggiore 3, I-20162 Milan, Italy
[2] Univ Valencia & Ciberhed, Hosp Univ & Politecn La Fe, Hepatol & Liver Transplantat Unit, Valencia, Spain
[3] Univ Milano Bicocca, Res Ctr Publ Hlth CESP, Monza, Italy
[4] Univ Milano Bicocca, Sch Med & Surg, Digest Dis Sect, Milan, Italy
[5] Univ Milano Bicocca, Sch Med & Surg, Int Ctr Digest Hlth, Milan, Italy
[6] Yale Univ, Ctr Liver, Dept Med, New Haven, CT USA
[7] Univ Vienna, Div Transplantat, Dept Surg, Vienna, Austria
[8] Molinette Mauriziano Hosp, LiverTransplantat Ctr, Gastrohepatol Unit, AOU Citta Salute & Sci Torino, Turin, Italy
[9] Univ Bologna, St Orsola Malpighi Hosp, Liver & Multiorgan Transplantat, Bologna, Italy
[10] Maggiore Univ Hosp, Div Digest Dis, Milan, Italy
[11] Mediterranean Inst Transplant, Palermo, Italy
[12] CHU St Eloi, Dept Hepatol Gastroenterol & Liver Transplant, Montpellier, France
[13] Univ Paris 11, Paul Brousse Hosp, AP HP, Ctr Hepatobiliaire, Villejuif, France
[14] Papa Giovanni XXIII Hosp, Gastroenterol & Transplant Hepatol, Bergamo, Italy
[15] Paris Est Univ, Henri Mondor Hosp, AP HP, Dept Hepatol, Creteil, France
[16] Paris Est Univ, Henri Mondor Hosp, AP HP, Liver Transplant Unit, Creteil, France
[17] Erasmus MC, Univ Med Ctr Rotterdam, Div HPB & Transplant Surg, Dept Surg, Rotterdam, Netherlands
[18] Univ Birmingham, Dept HPB Surg & Liver Transplantat, Birmingham B15 2TT, W Midlands, England
关键词
Direct acting antivirals; Liver transplantation; Delisting; HCV; Cirrhosis; ANTIVIRAL THERAPY; SOFOSBUVIR; CIRRHOSIS; RECURRENCE;
D O I
10.1016/j.jhep.2016.05.010
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: All oral direct acting antivirals (DAA) have been shown to improve the liver function of patients with decompensated cirrhosis but it is presently unknown whether this clinical improvement may lead to the delisting of some patients. The aim of this study was to assess if and which patients can be first inactivated due to clinically improvement and subsequently delisted in a real life setting. Methods: 103 consecutive listed patients without hepatocellular carcinoma were treated with different DAA combinations in 11 European centres between February 2014 and February 2015. Results: The cumulative incidence of inactivated and delisted patients by competing risk analysis was 15.5% and 0% at 24 weeks, 27.6% and 10.3% at 48 weeks, 33.3% and 19.2% at 60 weeks. The 34 patients who were inactivated showed a median improvement of 3.4 points for MELD (delta MELD, p < 0.0001) and 2 points for Child-Pugh (CP) (delta-CP, p < 0.0001). Three variables emerged from the most parsimonious multivariate competing risk model as predictors of inactivation for clinical improvement, namely, baseline MELD classes (MELD 16-20: HR = 0.120; p = 0.0005, MELD > 20: HR = 0.042; p < 0.0001), delta MELD (HR = 1.349; p < 0.0001) and delta albumin (HR = 0.307; p = 0.0069) both assessed after 12 weeks of DAA therapy. Conclusions: This study showed that all oral DAAs were able to reverse liver dysfunction and favoured the inactivation and delisting of about one patient out-of-three and one patient out-of-five in 60 weeks, respectively. Patients with lower MELD scores had higher chances to be delisted. The longer term benefits of therapy need to be ascertained. Lay summary: The excellent efficacy and safety profile of the new drugs against Hepatitis C virus, "direct acting antivirals" or DAAs, have made antiviral therapy possible also for patients with advanced liver disease and for those on the waiting list for liver transplantation (LT). This study shows for the first time that the DAAs may lead to a remarkable clinical improvement allowing the delisting of one patient out of 5. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
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页码:524 / 531
页数:8
相关论文
共 12 条
[1]  
Afdhal N, 2015, 2015 INT LIV C 50 AN
[2]   Liver transplantation for HBV-related cirrhosis in Europe: An ELTR study on evolution and outcomes [J].
Burra, Patrizia ;
Germani, Giacomo ;
Adam, Rene ;
Karam, Vincent ;
Marzano, Alfredo ;
Lampertico, Pietro ;
Salizzoni, Mauro ;
Filipponi, Franco ;
Klempnauer, Jurgen L. ;
Castaing, Denis ;
Kilic, Murat ;
De Carlis, Luciano ;
Neuhaus, Peter ;
Yilmaz, Sezai ;
Paul, Andreas ;
Pinna, Antonio D. ;
Burroughs, Andrew K. ;
Russo, Francesco P. .
JOURNAL OF HEPATOLOGY, 2013, 58 (02) :287-296
[3]   An application of changepoint methods in studying the effect of age on survival in breast cancer [J].
Contal, C ;
O'Quigley, J .
COMPUTATIONAL STATISTICS & DATA ANALYSIS, 1999, 30 (03) :253-270
[4]   Sofosbuvir and Ribavirin Prevent Recurrence of HCV Infection After Liver Transplantation: An Open-Label Study [J].
Curry, Michael P. ;
Forns, Xavier ;
Chung, Raymond T. ;
Terrault, Norah A. ;
Brown, Robert, Jr. ;
Fenkel, Jonathan M. ;
Gordon, Fredric ;
O'Leary, Jacqueline ;
Kuo, Alexander ;
Schiano, Thomas ;
Everson, Gregory ;
Schiff, Eugene ;
Befeler, Alex ;
Gane, Edward ;
Saab, Sammy ;
McHutchison, John G. ;
Subramanian, G. Mani ;
Symonds, William T. ;
Denning, Jill ;
McNair, Lindsay ;
Arterburn, Sarah ;
Svarovskaia, Evguenia ;
Moonka, Dilip ;
Afdhal, Nezam .
GASTROENTEROLOGY, 2015, 148 (01) :100-U519
[5]   A proportional hazards model for the subdistribution of a competing risk [J].
Fine, JP ;
Gray, RJ .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1999, 94 (446) :496-509
[6]   Impact of direct acting antiviral therapy in patients with chronic hepatitis C and decompensated cirrhosis [J].
Foster, Graham R. ;
Irving, William L. ;
Cheung, Michelle C. M. ;
Walker, Alex J. ;
Hudson, Benjamin E. ;
Verma, Suman ;
McLauchlan, John ;
Mutimer, David J. ;
Brown, Ashley ;
Gelson, William T. H. ;
MacDonald, Douglas C. ;
Agarwal, Kosh .
JOURNAL OF HEPATOLOGY, 2016, 64 (06) :1224-1231
[7]   A CLASS OF K-SAMPLE TESTS FOR COMPARING THE CUMULATIVE INCIDENCE OF A COMPETING RISK [J].
GRAY, RJ .
ANNALS OF STATISTICS, 1988, 16 (03) :1141-1154
[8]  
Jacobson LM, 2015, 2015 INTERNATIONAL CONFERENCE ON PLANARIZATION/CMP TECHNOLOGY (ICPT)
[9]   Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis [J].
Jang, Jeong Won ;
Choi, Jong Young ;
Kim, Young Seok ;
Woo, Hyun Young ;
Choi, Sung Kyu ;
Lee, Chang Hyeong ;
Kim, Tae Yeob ;
Sohn, Joo Hyun ;
Tak, Won Young ;
Han, Kwang-Hyub .
HEPATOLOGY, 2015, 61 (06) :1809-1820
[10]  
Manns M, 2016, LANCET INFECT DIS