Retreatment of patients with chronic hepatitis C, subtype 1b and cirrhosis, who failed previous direct-acting antiviral therapy including first- and second-generation NS5A inhibitors with ombitasvir/paritaprevir/ritonavir, dasabuvir+sofosbuvir+ribavirin.

Abstract

The use of direct-acting antiviral agents (DAAs) in patients with chronic HCV genotype 1 infection results in sustained virologic response (SVR) rates of 95%-97%, but 3%-5% of patients experience virologic failure. We observed 17 patients infected with HCV subtype 1b who failed previous treatment with DAA, including 13 subjects (76.5%) with liver cirrhosis. Twelve subjects (70.6%) previously received NS5A inhibitors of the first generation (ledipasvir or daclatasvir) and five subjects (29.4%) - the second generation (velpatasvir). All patients were retreated with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutations (L31M/V/I and/or Y93H), and on the generation of previously used NS5A inhibitor. Observed SVR12 rates were as follows: 94.1% (16/17 patients) overall; 100% in patients without cirrhosis (n=4) vs 92.3% in those with cirrhosis (n=13); 100% with single L31M/V/I or Y93H mutation (n=7) vs 88.9% with double mutations (n=9); 100% in patients who previously failed first generation (n=12) vs 80.0% in those failed second-generation NS5A inhibitors (n=5). Retreatment with 3D+0SOF+RBV was highly effective and safe in patients with chronic HCV GT1b infection who failed previous use of NS5A inhibitors. Fibrosis stage, baseline presence of NS5A RAS mutations and the generation of previously used NS5A inhibitors may impact the probability of achieving SVR12 , but statistical significance was not demonstrated in our small retrospective cohort. Further studies in a larger population are needed to confirm or not the predictive value of these baseline factors.