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Use of direct-antiviral agents helps overcome hepatitis C recurrence in liver transplant patients

New study showcases efficacy and safety of sofosbuvir and daclatasvir in patients with recurrent hepatitis C

2015-04-25
(Press-News.org) April 25, 2015, Vienna, Austria: New data presented today at The International Liver Congress™ 2015, supports the use of sofosbuvir (SOF)- and daclatasvir (DCV)-based regimens in patients with recurrence of the hepatitis C virus (HCV) following liver transplantation (LT). The results are based on data from patients with HCV being treated with second-generation DAAs in the large French prospective ANRS CO23 CUPILT study. Among them, 296 patients were treated with a combination of SOF+DCV, with or without ribavirin.

SOF- and DCV-based regimens offered high rates of sustained virologic response (SVR) coupled with good tolerance. The presented results focus on 130 patients who achieved SVR12; end of treatment therapy and SVR12 rates are 98% and 96%, respectively.

"The use of interferon-free regimens using DAAs has dramatically improved the management of liver transplant patients infected with HCV. The outstanding efficacy and safety results that sofosbuvir- and daclatasvir-based regimens demonstrated in patients with recurrent hepatitis C are impressive and will help us identify optimal treatment strategies using these new therapies," said Audrey Coilly, MD, Paul Brousse Hospital, Villejuif.

"HCV recurrence is one of the main complications following liver transplantation and can seriously affect patient survival. So it is very encouraging to see such positive results from this study. We hope it will mean more successful future transplants for people with chronic HCV infection," said Professor Tom Hemming Karlsen, Scientific Committee Member, European Association for the Study of the Liver.

Serious adverse events were experience by 23% of patients, mainly haematological events in patients treated with ribavirin. Interestingly, attention should be paid to renal function, as a significant decrease has been observed during therapy. Although no drug-drug interaction has been remarked, changes in dosage of immunosuppressive drugs in more than 50% of patients still require close monitoring.



INFORMATION:

About The International Liver Congress™ This annual congress is the biggest event in the EASL calendar, attracting scientific and medical experts from around the world to learn about the latest in liver research. Specialists share research studies and findings, and discuss the hottest topics related to liver disease. This year, the congress is expected to attract approximately 10,000 delegates from all corners of the globe. 2015 is a very special year for EASL and the hepatology community as they will celebrate the 50th annual meeting. The International Liver Congress™ takes place from April 22-26, 2015, Vienna, Austria.

About EASL Since EASL's foundation in 1966, this not-for-profit organisation has grown to over 4,000 members from more than 100 countries around the world. EASL is the leading liver association in Europe, it attracts the foremost hepatology experts and has an impressive track record in promoting research in liver disease, supporting wider education and promoting changes in European liver policy.

Contact For more information, please contact the ILC Press Office at: ilc.press@easloffice.eu or
+44 (0)20 3580 5444

General session 3, Hall D

Presentation time: 10.15-10.30
Presenter: Audrey Coily (France)
Abstract G15: THE ASSOCIATION OF SOFOSBUVIR AND DACLATASVIR FOR TREATING SEVERE RECURRENCE OF HCV INFECTION AFTER LIVER TRANSPLANTATION: RESULTS FROM A LARGE FRENCH PROSPECTIVE MULTICENTRIC ANRS CO23 CUPILT COHORT

THE ASSOCIATION OF SOFOSBUVIR AND DACLATASVIR FOR TREATING SEVERE RECURRENCE OF HCV INFECTION AFTER LIVER TRANSPLANTATION: RESULTS FROM A LARGE FRENCH PROSPECTIVE MULTICENTRIC ANRS CO23 CUPILT COHORT

Audrey Coilly* 1, 2, Claire Fougerou3, Victor De Ledinghen4, Pauline Houssel-Debry3, Christophe Duvoux5, Vincent Di Martino6, Sylvie Radenne7, Nassim Kamar8, Louis D'Alteroche9, Vincent Leroy10, Valérie Canva11, Pascal Lebray12, Christophe Moreno13, Jerome Dumortier14, Christine Silvain15, Camille Besch16, Philippe Perre17, Danielle Botta-Fridlund18, Rodolphe Anty19, Alexandra Rohel20, Alain Renault21, Hélène Danjou21, Jean-Charles Duclos-Vallee1, 2, Georges-Philippe Pageaux22 1AP-HP Hopital Paul Brousse, 2UMR-S 785, Univ Paris-Sud - INSERM, Villejuif, 3CHU de Rennes, Rennes, 4CHU de Bordeaux, Bordeaux, 5AP-HP Hopital Henri-Mondor, Creteil, 6CHU de Besançon, Besançon, 7HCL - Hopital de la Croix Rousse, Lyon, 8CHU de Toulouse, Toulouse, 9CHU de Tours, Tours, 10CHU de Grenoble, Grenoble, 11CHRU de Lille, Lille, 12AP-HP Groupe hospitalier Pitie-Salpetriere, Paris, 13Universite Libre de Bruxelles - Hopital Erasme, Brussels, 14HCL - Hopital Edouard Herriot, Lyon, 15CHU de Poitiers, Poitiers, 16CHRU de Strasbourg, Strasbourg, 17Centre hospitalier departemental de Vendee, La Roche sur Yon, 18AP-HM CHU La Conception, Marseille, 19CHU de Nice - Hopital de l'Archet, Nice, 20ANRS, Paris, 21CHU de Rennes - Hopital Pontchaillou, Rennes, 22CHU de Montpellier - Hopital Saint Eloi, Montpellier, France Background and Aims: HCV recurrence is a main complication following liver transplantation (LT) impacting graft and patient survival. The recent approval of IFN-free regimen using direct antiviral agents (DAA) has radically changed the management of liver transplant recipients. However, the optimal strategy remains to be determined. The aim of this study was to assess efficacy and safety of sofosbuvir (SOF) and daclatasvir (DCV)-based regimens in this setting.

Methods: The ANRS CO23 CUPILT study is a prospective cohort including currently 335 patients (pts) with HCV recurrence and treated with 2nd generation DAA. All pts treated with SOF+DCV±ribavirin (RBV) between Jul. 2013 and Nov. 2014 were included in the present study.

Results: This study enrolled 190 liver recipients (male: 76%, mean age 59±9years [33-83]), with an active HCV recurrence (G1:116, G3:17, G4:12, G5:1), in 19 centers. The mean delay between LT and starting therapy was 74.2±73.5 months [1.8-339.4]. Treatment duration was 24 weeks (wk) in 84% of pts. RBV was given in 67 (38%) pts. Indication was severe HCV recurrence, including 32 cirrhotic pts, and 11 cholestatic hepatitis. Eighty-three (46%) pts were non-responders to a previous course of therapy post-LT (including Peg-FN/RBV: 64 (77%); 1rst generation PI based regimen: 16 (19%)). Eighty-nine percent of pts received cyclosporine (32%) or tacrolimus (68%). At baseline, HCV viral load, GGT and hemoglobin levels were 6.4±0.7log10 IU/mL [4.2-8.4], 381.8±573.4 IU/L [16-3561], 12.8±2.3g/dL [7.8-17.9], respectively. After 4 wks, a complete virological response was obtained in 36/178 (23%) pts. One pt experienced a virological breakthrough (wk 8); among 115 pts who have completed the treatment, the end of treatment response was achieved in 114 (99%). One pt relapsed at wk 4 post-treatment; 62/64 (97%) and 42/44 (95%) pts achieved SVR4 and 12, respectively. Twenty-three (12%) pts experienced serious adverse events (SAE), leading to 2 premature discontinuations (wk 1 and 2) including 1 death (diabetic coma). Most common SAE were hematological toxicity. Anemia occurred in 6 (3%) pts, all treated with RBV. Eight non-severe infections occurred. Two non-severe biopsy-proven acute rejections occurred after treatment discontinuation. No drug-drug interaction was reported. Conclusions: SOF and DCV based regimens showed excellent results combining high rate of SVR4 and 12 (97% and 95%, respectively) and a good tolerance. Final results will be presented.

Disclosure of Interest: A. Coilly: Sponsored Lectures (National or International): Novartis, Astellas, Janssen, Bristol-Myers-Squibb, Merck Sharp & Dohme, Gilead, Roche, C. Fougerou: : None Declared, V. De Ledinghen: : None Declared, P. Houssel-Debry: : None Declared, C. Duvoux: : None Declared, V. Di Martino: : None Declared, S. Radenne: : None Declared, N. Kamar: : None Declared, L. D'Alteroche: : None Declared, V. Leroy: : None Declared, V. Canva: : None Declared, P. Lebray: : None Declared, C. Moreno: : None Declared, J. Dumortier: : None Declared, C. Silvain: : None Declared, C. Besch: : None Declared, P. Perre: : None Declared, D. Botta-Fridlund: : None Declared, R. Anty: : None Declared, A. Rohel: : None Declared, A. Renault: : None Declared, H. Danjou: : None Declared, J.-C. Duclos-Vallee: : None Declared, G.-P. Pageaux: : None Declared



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[Press-News.org] Use of direct-antiviral agents helps overcome hepatitis C recurrence in liver transplant patients
New study showcases efficacy and safety of sofosbuvir and daclatasvir in patients with recurrent hepatitis C