Real life rates of sustained virological response (SVR) and predictors of relapse following DAA treatment in genotype 3 (GT3) patients with advanced fibrosis/cirrhosis

Alessandra Mangia, Ruggero Losappio, Giovanni Cenderello, Domenico Potenza, Michele Mazzola, Giulio De Stefano, Natalia Terreni, Massimiliano Copetti, Nicola Minerva, Valeria Piazzola, Donato Bacca, Vincenzo Palmieri, Fernando Sogari, Rosanna Santoro, Alessandra Mangia, Ruggero Losappio, Giovanni Cenderello, Domenico Potenza, Michele Mazzola, Giulio De Stefano, Natalia Terreni, Massimiliano Copetti, Nicola Minerva, Valeria Piazzola, Donato Bacca, Vincenzo Palmieri, Fernando Sogari, Rosanna Santoro

Abstract

Background: Treatment of GT3 remains challenging compared to other genotypes.

Aims: To explore real life SVR rates and to identify predictors of virological failure across the most recently used Direct acting antiviral (DAA) regimens in a large cohort of Italian patients with cirrhosis or advanced fibrosis (F3 or F4).

Methods: Between May 2015 and June 2017, the combinations of sofosbuvir (SOF) plus daclatasvir (DCV) ± RBV and SOF plus velpatasvir (VEL) ± RBV become available in our Country. Patients were treated following Italian guidelines within a protocol implemented by 11 centers working together on genetics.

Results: Of 336 patients, 38.1% were Peg/IFN-experienced. SOF/DCV was used in 65.1%, SOF/VEL in the remaining. Overall SVR12 was 90.2% ranging from 87.2% after SOF/DCV to 95.7% after SOF/VEL (p = 0.012). No additional benefits of RBV use were observed for both regimens. 155 patients (46.1%) had cirrhosis. SVR12 was 87.1% (135/155) for cirrhotic patients and 92.8% (169/182) for non-cirrhotic (p = 0.09). NS5A-RASs were present at baseline in 6.4% of patients, PNPLA3GG and IL28BCC genotypes in 7.3% and 33.0%, respectively. No association between favorable genetics and SVR12 was observed. Predictors of relapse were: history of Peg/IFN/RBV failure (OR = 6.34, 95% CI 2.04-19.66, P = .001), baseline NS5A-RASs (OR = 8.7, 95% CI 1.58-47.92, P = 0.013) and treatment regimen (OR = 5.57 95% CI 1.64-18.95.96, P = 0.006).

Conclusions: Our real-world results validate the efficacy of current GT3 IFN-free regimens suggesting that, among patients with severe disease, Peg/IFN/RBV experience and NS5A associated RASs are predictors of relapse. Their relevance can be expected to decline with the use of SOF/VEL. (250).

Conflict of interest statement

Alessandra Mangia declares the following conflicts: Advisory for Gilead Sciences, MSD, Janssen, BMS; Research funding: MSD, Gilead Sciences, Janssen; Speaking and Teaching: MSD, Gilead Sciences, BMS. The other authors have no conflicts of interest to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study flow chart.
Fig 1. Study flow chart.
Fig 2. Sustained Virological Response (SVR) by…
Fig 2. Sustained Virological Response (SVR) by DAA treatment regimen in the subgroup of patients with cirrhosis.
The figure shows Sustained Virological Response (SVR) rates in patients with cirrhosis treated with SOF/DCV or SOF/VEL without RBV.
Fig 3. SVR by RBV.
Fig 3. SVR by RBV.
The figure shows Sustained Virological Response (SVR) rates with (1) or without (2) RBV in patients treated with SOF/DCV (A) or with SOF/DCV (B).

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Source: PubMed

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