Multicentre experience using daclatasvir and sofosbuvir to treat hepatitis C recurrence - The ANRS CUPILT study

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• 作者：Audrey Coilly¹ ; ² ; ³ ; ⁴ ; ^{audrey.coilly@aphp.fr" class="auth_mail" title="E-mail the corresponding author} ; Claire Fougerou-Leurent⁵ ; ⁶ ; Victor de Ledinghen⁷ ; Pauline Houssel-Debry⁸ ; Christophe Duvoux⁹ ; Vincent Di Martino¹⁰ ; Sylvie Radenne¹¹ ; Nassim Kamar¹² ; Louis D&rsquo ; Alteroche¹³ ; Vincent Leroy¹⁴ ; Valé ; rie Canva¹⁵ ; Pascal Lebray¹⁶ ; Christophe Moreno¹⁷ ; Jé ; rô ; me Dumortier¹⁸ ; Christine Silvain¹⁹ ; Camille Besch²⁰ ; Philippe Perre²¹ ; Danielle Botta-Fridlund²² ; Rodolphe Anty²³ ; Claire Francoz²⁴ ; Armando Abergel²⁵ ; Maryline Debette-Gratien²⁶ ; Filomena Conti¹⁶ ; Franç ; ois Habersetzer²⁷ ; Alexandra Rohel²⁸ ; Emilie Rossignol⁵ ; ⁶ ; Hé ; lè ; ne Danjou⁵ ; ⁶ ; Anne-Marie Roque-Afonso²⁹ ; ² ; ³ ; ⁴ ; Didier Samuel¹ ; ² ; ³ ; ⁴ ; Jean-Charles Duclos-Vallé ; e¹ ; ² ; ³ ; ⁴ ; Georges-Philippe Pageaux³⁰ ; for the ANRS C023 CUPILT study group
• 关键词：AE ; adverse events ; DAAs ; direct-acting antiviral agents ; DCV ; daclatasvir ; EOT ; end of treatment ; GFR ; glomerular filtration rate ; HCV ; hepatitis C virus ; HIV ; human immunodeficiency virus ; IMS ; immunosuppressive ; LLOQ ; lower limit of quantification ; LT ; liver transplantation ; MDRD ; modified diet in renal disease ; MELD ; model for end-stage liver disease ; PegIFN ; pegylated interferon ; RBV ; ribavirin ; SAE ; serious adverse events ; SOF ; sofosbuvir ; SVR ; sustained virological response ; TBC ; trough b
• 刊名：Journal of Hepatology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：4
• 页码：711-718
• 全文大小：881 K

文摘

HCV recurrence remains a major issue in the liver transplant field, as it has a negative impact on both graft and patient survival. The purpose of this study was to investigate the efficacy and safety of treating HCV recurrence with sofosbuvir (SOF) and daclatasvir (DCV) combination therapy.

Methods

From October 2013 to March 2015, 559 liver recipients were enrolled in the prospective multicentre France REcherche Nord&Sud Sida-hiv Hépatites (ANRS) Compassionate use of Protease Inhibitors in viral C Liver Transplantation cohort. We selected 137 patients with an HCV recurrence receiving SOF and DCV, whatever the genotype or fibrosis stage. The use of ribavirin and the duration of therapy were at the investigator’s discretion. The primary efficacy end point was a sustained virological response (SVR) 12 weeks after the end of treatment.

Results

The SVR rate 12 weeks after completing treatment was 96% under the intention-to treat analysis and 99% when excluding non-virological failures. Only two patients experienced a virological failure. The serious adverse event (SAE) rate reached 17.5%. Four patients (3%) stopped their treatment prematurely because of SAEs. Anaemia was the most common AE, with significantly more cases in the ribavirin group (56% vs. 18%; p <0.0001). A slight but significant reduction in creatinine clearance was reported. No clinically relevant drug-drug interactions were noted, but 52% of patients required a change to the dosage of immunosuppressive drugs.

Conclusions

Treatment with SOF plus DCV was associated with a high SVR12 and low rates of serious adverse events among liver recipients with HCV recurrence.

Lay summary

The recurrence of hepatitis C used to be the first cause of graft failure in infected liver transplanted recipients. Our study demonstrates the great efficacy of one combination of new all-oral direct-acting antiviral, sofosbuvir and daclatasvir, to treat the recurrence of hepatitis C on the graft. Ninety-six per cent of recipients were cured. The safety profile of this combination seemed to be good, especially no relevant drug-drug interaction with immunosuppressive drugs.