Abstract
BackgroundTreatment of GT3 remains challenging compared to other genotypes.AimsTo 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).MethodsBetween 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.ResultsOf 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).ConclusionsOur 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).
Highlights
Genotype 3 (GT3) represents one of the last challenges in the field of HCV treatment [1]
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 Resistance associated substitutions (RASs) are predictors of relapse
DCV/SOF [4] and, more recently, SOF/ VEL [5,6] led to an increase in the cure rate over the combination of SOF/RBV, yet the proportion of GT3 responding to Direct acting antiviral (DAA) remains lower than for other genotypes [7]
Summary
GT3 represents one of the last challenges in the field of HCV treatment [1]. The association with steatosis, responsible for an accelerated progression to fibrosis, and with rates of HCC higher than in other genotypes [2] justifies the efforts to treat GT3-infected patients as early as possible—these representing 25% of all infections [3]. IL28BCC and PNPLA3GG genetic polymorphisms are considered predictors either of treatment response or progression of steatosis. Rs12979860 IL28BCC polymorphism has been associated with both, higher responses to IFN-based therapies and advanced disease in chronic HCV infection [8,9]. The rs738409 PNPLA3GG polymorphism is a risk factor for fatty liver and a marker of steatosis to fibrosis progression for chronic HCV-infected patients [10].
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