Rescue Therapy after Failure of HCV Antiviral Treatment with Interferon-Free Regimens

Abstract

Direct-acting antivirals (DAA) regimens have provided hope for eliminating hepatitis C virus (HCV) infection. Patients following ineffective therapy with DAA, especially those previously treated with inhibitors of non-structural protein 5A (NS5A), remain a challenge. The study aimed to assess the effectiveness of DAA pangenotypic options in patients after failure of NS5A containing genotype-specific regimens. The analysis included 120 patients selected from the EpiTer-2 database with data on 15675 HCV-infected individuals treated with IFN-free therapies from 1 July 2015 to 30 June 2022 at 22 Polish hepatology centres. The majority of them were infected with genotype (GT) 1b (85.8%) and one-third was diagnosed with fibrosis F4. Among the rescue pangenotypic regimens, the most commonly used was the sofosbuvir/velpatasvir (SOF/VEL) ± ribavirin (RBV) combination. The sustained virologic response, which was a measure of treatment effectiveness, was achieved by 102 patients, resulting in cure rate of 90.3% in the per protocol analysis. All 11 non-responders were infected with GT1b, 7 were diagnosed with cirrhosis, and 9 were treated with SOF/VEL±RBV. We demonstrated the high effectiveness of the pangenotypic rescue options in patients after genotype specific NS5A-containing regimens failures, identifying cirrhosis as a negative prognostic factor of treatment effectiveness.

Pangenotypic triple versus double therapy in HCV-infected patients after prior failure of direct-acting antivirals

“…According to international and national recommendations of scientific societies supported by the results of clinical trials, the first-line retreatment option in such patients is the triple combination of DAA, VVS [14,18,[20][21][22]. However, in the setting of routine clinical practice, due to limitations in the availability of a triple rescue regimen, double options have been used, especially in patients with risk factors for liver disease progression [6,23,24]. This was the approach used in our study, in which the majority of patients with a history of failed DAA therapy received a double pangenotypic regimen for retreatment, with a cure rate of 89%.…”

“…The introduction of direct-acting antivirals (DAA) for the treatment of hepatitis C virus (HCV) infections ensured the effectiveness of therapy in patients infected with the dominant genotype 1b HCV at the level of 98%, which even in difficult-to-treat subpopulations exceeds 90% [ 1 - 4 ]. However, despite such excellent treatment effects, there are still patients in whom treatment does not allow for a sustained virologic response (SVR) [ 5 , 6 ]. In such situations, according to the guidelines, it is reasonable to retry treatment using an alternative therapy [ 7 , 8 ].…”

“…Initially, when treatment failures occurred after genotype-specific DAA regimens, retherapy with alternative drugs from the same group was used. However, soon, the new two-drug pangenotypic therapeutic options glecaprevir/pibrentasvir (GP) and velpatasvir/sofosbuvir (VS) became the natural choice for patients not responding to genotype-specific treatment [ 6 ]. Unfortunately, failures also occur among those treated with dual pangenotypic therapies, but the vast majority of them can be successfully re-treated with the use of an alternative dual pangenotypic option.…”