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Preliminary results of a Daclatasvir (DCV) based treatment protocol (DCV+Sof, DCV+Simeprevir) in LT recipients with severe recurrent HCV
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All participants received DCV 60 mg per day for up to 24 weeks as part of a compassionate use protocol.
Local safety and efficacy labs as well as clinical data were obtained from site investigators. .......
The most commonly used antiviral regimens were DCV + SOF + RBV (n= 23) and DCV + SMV + RBV (n=7).
2 patients had HIV & HCV, coinfected.
Reported by Jules Levin
AASLD 2014 Nov 7-11 Boston
Program abstract:
High efficacy and favorable safety profile of Daclatasvir based all oral antiviral therapy in liver Transplant
recipients with severe recurrent HCV.
R. Bahirwani, R. Reddy, University of Pennysylvania, Philadelphia, Pennsylvania,
UNITED STATES|R.J. Fontana, University of Michigan, Ann Arbor, Michigan, UNITED STATES|K. Herzer, University
Hospital Essen, Essen, GERMANY|P. Ferenci, Medical University of Vienna, Vienna, AUSTRIA|A. Moreno, Ramon
and Cajal Hospital, Madrid, SPAIN|R. Brown, Columbia University, New York , New York, UNITED STATES|K.
Chacko, Montefiore Medical Center, New York , New York, UNITED STATES|C. Durand, The Johns Hopkins Medical
Institutions, Baltimore, Maryland, UNITED STATES|S. Joshi, Ochsner Health System, Jefferson, Louisiana, UNITED
STATES|V. Knop, Klinikum der J. W. Goethe-Universität, Frankfurt, GERMANY|M. Londono, Hospital Clinic
Barcelona, Barcelona, SPAIN|A.M. Pellicelli, San Camillo-Forlanini Hospital, Rome, ITALY|A. Mubarak, Methodist
Dallas Medical Center, Dallas, Texas, UNITED STATES|C.P. Berg, University Hospital Tübingen, Tubingen,
GERMANY|R. Lionetti, M. Montalbano, I.R.C.C.S. Lazzaro Spallanzani, Rome, ITALY|M. Loiacono, AOU S. Giovanni
Battista10, Turin, ITALY|
Interferon based therapies have limited efficacy and are poorly tolerated in liver transplant (LT)
recipients with recurrent HCV. Daclatasvir (DCV), a potent NS5A inhibitor, has shown promising efficacy and safety
results when combined with sofosbuvir (SOF) and simeprevir (SMV) + ribavirin (RBV). The aim of this study is to
describe the preliminary results of a DCV based treatment protocol in LT recipients with severe recurrent HCV.
METHODS: All participants received DCV 60 mg per day for up to 24 weeks as part of a compassionate use protocol.
Local safety and efficacy labs as well as clinical data were obtained from site investigators.
RESULTS: As of 7/1/14,
106 subjects had enrolled and end of treatment data were available in 30 patients. The mean time from LT to initiation
of DCV therapy was 48.1 + 16.6 months (40% < 1 year postLT). Mean subject age was 57.5 + 8.9 years, 60% male,
80% Caucasian, and 10% were hospitalized at enrollment. 57% had fibrosing cholestatic HCV, 30% had cirrhosis, and
67% had received prior antiviral therapy. The mean MELD score was 14.2 + 8.1; % CTP A/B/C was 50%/20%/27%.
All of the patients had HCV genotype 1 (47% 1a, 50% 1b) and the mean baseline HCV RNA was 29 x 6 log10 IU/ml.
The most commonly used antiviral regimens were DCV + SOF + RBV (n= 23) and DCV + SMV + RBV (n=7). Baseline
meds included tacrolimus (77%), cyclosporine (17%), and prednisone (17%). 6 subjects with a median pretreatment
MELD of 23.3 (r: 6.4-40.0) died at a median of 4 weeks of DCV therapy (r: 0 to 16 wks) from liver failure or sepsis not
attributed to DCV.
At the end of DCV therapy in the 24 survivors, 79% were HCV-RNA (-), 21% HCV-RNA (+) but < 43
IU/ml. At week 12 post-DCV therapy, 38% were HCV-RNA (-), 8% HCV-RNA (+) but < 43 IU/ml, and 50% pending.
One patient who received DCV + SMV for 24 wks had a HCV-RNA (-) at end of treatment and virological relapse at
week 12 post-therapy but remains stable. The mean CTP and MELD scores improved from baseline to last follow-up
(CTP: 7.3 vs 5.8, p=0.004, MELD: 11.9 vs 9.8, p=0.0532) in 20 (CTP) and 21 (MELD) evaluable patients with a
median f/u of 28 weeks. There were 13 total SAEs reported but no instances of acute rejection or immunosuppressant
toxicity due to low or high CNI levels, respectively.
CONCLUSION: DCV based all oral antiviral therapy results in a
high rate of on-treatment and end of treatment virological response in immunosuppressed LT recipients with severe
recurrent HCV. The majority of DCV treated patients experienced stabilization or improvement in their laboratory and
clinical status. Although post-therapy relapse is infrequent, continued virological assessment is ongoing.
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