Effectiveness and Safety of Sofosbuvir-based Regimens Plus an NS5A Inhibitor for Patients With HCV Genotype 3 Infection and Cirrhosis

Results of a Multicenter Real-life Cohort

S. Alonso; M. Riveiro-Barciela; I. Fernandez; D. Rincón; Y. Real; S. Llerena; F. Gea; A. Olveira; C. Fernandez-Carrillo; B. Polo; J. A. Carrión; A. Gómez; M. J. Devesa; C. Baliellas; Á. Castro; J. Ampuero; R. Granados; J. M. Pascasio; A. Rubín; J. Salmeron; E. Badia; J. M. M. Planas; S. Lens; J. Turnes; J. L. Montero; M. Buti; R. Esteban; C. M. Fernández-Rodríguez

Disclosures

J Viral Hepat. 2017;24(4):304-311. 

In This Article

Abstract and Introduction

Abstract

Patients with HCV genotype 3 (GT3) infection and cirrhosis are currently the most difficult to cure. We report our experience with sofosbuvir+daclatasvir (SOF+DCV) or sofosbuvir/ledipasvir (SOF/LDV), with or without ribavirin (RBV) in clinical practice in this population. This was a multicenter observational study including cirrhotic patients infected by HCV GT3, treated with sofosbuvir plus an NS5A inhibitor (May 2014-October 2015). In total, 208 patients were included: 98 (47%) treatment-experienced, 42 (20%) decompensated and 55 (27%) MELD score >10. In 131 (63%), treatment was SOF+DCV and in 77 (37%), SOF/LDV. Overall, 86% received RBV. RBV addition and extension to 24 weeks was higher in the SOF/LDV group (95% vs 80%, P=.002 and 83% vs 72%, P=.044, respectively). A higher percentage of decompensated patients were treated with DCV than LDV (25% vs 12%, P=.013). Overall, SVR12 was 93.8% (195/208): 94% with SOF+DCV and 93.5% with SOF/LDV. SVR12 was achieved in 90.5% of decompensated patients. Eleven treatment failures: 10 relapses and one breakthrough. RBV addition did not improve SVR (RR: 1.08; P=.919). The single factor associated with failure to achieve SVR was platelet count <75×10E9/mL (RR: 3.50, P=.019). In patients with MELD <10, type of NS5A inhibitor did not impact on SVR12 (94% vs 97%; adjusted RR: 0.49). Thirteen patients (6.3%) had serious adverse events, including three deaths (1.4%) and one therapy discontinuation (0.5%), higher in decompensated patients (16.7% vs 3.6%, P<.006). In patients with GT3 infection and cirrhosis, SVR12 rates were high with both SOF+DCV and SOF/LDV, with few serious adverse events.

Introduction

Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are at a higher risk of progression to liver disease and development of hepatocellular carcinoma than patients with other HCV genotypes.[1–3] Hence, this population should be prioritized to receive effective antiviral therapy. Direct-acting antiviral (DAA) agents have significantly improved the efficacy and tolerability of HCV treatment. However, as compared to other genotypes, the efficacy of DAA combinations is lower in patients with GT3 infection and liver cirrhosis.

Sofosbuvir[4] (SOF), a pangenotypic NS5B inhibitor, and daclatasvir[5] (DCV), an NS5A inhibitor, are active against GT3 infection, whereas ledipasvir[6] (LDV), another NS5A inhibitor, has shown lower in vitro activity against GT3.[7] There are few studies evaluating these regimes in GT3-associated cirrhosis in real practice settings.

The ALLY-3 clinical trial assessed the efficacy of the SOF+DCV combination for 12 weeks in GT3 patients with and without cirrhosis. The sustained virological response rate after 12 weeks of therapy (SVR12) in cirrhotic patients was 63% (58% in treatment-naïve [TN] and 69% in treatment-experienced [TE] patients).[8] A later study, ALLY-3+, was designed to evaluate the effect of adding ribavirin (RBV) and extending treatment duration to 16 weeks in patients with advanced fibrosis. SVR12 rates increased to 88% with SOF+DCV and RBV for 12 weeks, and to 86% with extension of therapy to 16 weeks.[9]

In a trial including 101 patients with GT3 infection, the fixed-dose combination of SOF/LDV without RBV achieved an SVR12 rate of 64% in naïve patients. Addition of RBV improved these results in noncirrhotic patients (100% TN vs 82% TE) and in patients with cirrhosis (100% TN vs 73% TE), although only 15 patients were included.[10]

In clinical practice, a larger amount of information is available for the SOF+DCV combination than for SOF/LDV. The French multicenter compassionate use programme in cirrhotic GT3 patients receiving SOF+DCV with or without RBV for 24 weeks reported SVR12 rates of 86% without RBV and 81% with RBV. Treatment of decompensated cirrhotic patients resulted in even lower SVR rates (approximately 70%).[11] The British expanded access programme focusing on decompensated GT3 patients reported SVR rates of 59% in 61 patients who received SOF/LDV and RBV for 12 weeks compared with 70% in 114 patients who received SOF+DCV and RBV for 12 weeks.[12] Data are limited regarding extending SOF/LDV and RBV therapy to 24 weeks in patients with cirrhosis. The aim of this study was to evaluate the effectiveness and safety of 12- and 24-week regimens of SOF plus an NS5A inhibitor (DCV or LDV) with or without RBV in a cohort of HCV GT3-infected patients with liver cirrhosis treated in a real-life multicenter setting.

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