Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort

Abstract

ObjectiveWe assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.DesignAdults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).ResultsOf the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.ConclusionsDCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.Trial registration numberNCT0209966.

Daclatasvir plus sofosbuvir, with or without ribavirin, for hepatitis C virus genotype 3 in a French early access programme

“…No additional benefit of RBV was observed in compensated or decompensated cirrhosis, although unrandomized treatment allocation and potential selection bias for RBV use makes it difficult to assess the significance of this. These data are consistent with other real‐world findings from the European Union compassionate use programme, in which cirrhotic patients (52% decompensated) treated with DCV+SOF+RBV for 24 weeks received no SVR12 benefit over those treated without RBV (88% vs 89%) 13. Other real‐world data in less clinically advanced patients with genotype 3 infection from the US Veterans Administration (VA) healthcare system14 and HCV‐TARGET observational study15 have demonstrated SVR rates of 81% and 82%, respectively, with a 12‐week regimen of SOF+RBV+pegIFN.…”

Potential Liver Transplant Recipients with Hepatitis C: Should They Be Treated Before or After Transplantation?

“…This is the group where the pros and cons need to be discussed with the patient and family and decision made regarding DAA treatment of transplantation. It may be recalled that even in other studies mentioned above, 31,59 improvement is mainly seen among those who have MELD score 15 or less and hardly anyone with MELD score >20 has shown significant improvement. This may signify a point of no return for liver decompensation as far as therapy for HCV is concerned and they will be better off receiving LT first and being treated later, rather than accept the risk of further worsening or that of HCC recurrence.…”

Direct-acting agents for hepatitis C virus before and after liver transplantation

“…There are no data on patients with Child Pugh class C decompensated cirrhosis. A European study (19) reported that 143 Child Pugh class B patients and 22 class C patients underwent sofosbuvir/daclastavir treatment with or without ribavirin for 24 weeks and achieved an SVR12 of 86% and 76%, respectively.…”