Pangenotypic direct‐acting antiviral agents for mixed genotype hepatitis C infection: A real‐world effectiveness analysis

Abstract

Background: Pangenotypic direct-acting antiviral agents (DAAs) glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL) are effective against all hepatitis C virus (HCV) genotype infections. However, data on pangenotypic DAA treatment for mixed genotype HCV infection are sparse. Methods: This is a retrospective, single site cohort study analyzing all patients with mixed HCV genotype infections treated with GLE/PIB or SOF/VEL from August 2018 to August 2020 in Chiayi Chang Gung Memorial Hospital, Taiwan. The primary study endpoint was sustained virologic response (SVR) 12 weeks after treatment cessation. We also reported adverse events (AEs). Results: A total of 108 patients with mixed infections of any two or three genotypes of 1a, 1b, 2, 3, and 6 received pangenotypic DAAs during the study period. A total of 67 patients received GLE/PIB and 41 received SOF/VEL. The evaluable population analysis revealed SVR rates of 94% (63/67) and 95.1% (39/41) for GLE/PIB and SOF/VEL therapy, respectively, and the per-protocol analysis revealed an SVR of 100% for both regimens. Four patients in the GLE/PIB group and two patients in the SOF/VEL were lost to follow-up. The most common AEs for GLE/PIB versus SOF/VEL therapy included pruritus (14.9% vs 2.4%), fatigue (6.0% vs 7.3%), abdominal discomfort (4.5% vs 7.3%), and acid reflux (3.0% vs 4.9%). DAA-related significant laboratory abnormalities occurred in three patients with > 1.5 × elevated bilirubin level in the GLE/PIB group. None of the above AEs resulted in DAA discontinuation. Conclusions: Pangenotypic DAAs are well tolerated by and yield high SVR rates in patients with mixed genotype HCV infection.

Pan-Genotypic Direct-Acting Antiviral Agents for Undetermined or Mixed-Genotype Hepatitis C Infection: A Real-World Multi-Center Effectiveness Analysis

“…In this multiple-center cohort study of mixed-genotype or genotype-undetermined HCV-infected patients receiving pan-genotypic DAA therapy, we found an overall SVR rate of 96.5% via PP analysis in a real-world setting. Despite the well-known treatment efficacy of these pan-genotypic DAAs in their landmark clinical trial setting [ 24 , 25 , 26 , 27 ], data on the effect of DAA treatment for these less frequently encountered HCV genotype populations are scarce [ 17 , 28 , 29 ]. In this study, we attempted to fill this knowledge gap on the DAA treatment of infection and demonstrated that the pan-genotypic DAA with either SOF/VEL or GLE/PIB are effective and safe for these patients in the real-world setting.…”

“…Determination of HCV genotype requires the use of PCR to hybridize to genotype-specific probe that allows understanding route of HCV infection of the patient and helps clinicians to determine the duration of interferon therapy [ 2 , 6 ] or choosing genotype-specific DAA therapy before the introduction of current pan-genotypic DAA therapy [ 14 , 18 , 19 , 32 ]. However, less than ten percent of the patients were infected with the mixed variant of the HCV, especially those infected with HIV or intravenous drugs users [ 17 , 21 , 33 , 34 , 35 ]. In this study, high rates of genotype mixtures of 1 + 6 (18.9%) were interesting because genotypes 1b and 2 were the most prevalent in Taiwan.…”

“…Such a simplified treatment pathway is particularly beneficial for people in the PWID population, homeless patients, migrants, and incarcerated people in the era of the COVID-19 pandemic. Recently, Chiu et al [ 36 ] reported an SVR rate that ranged from 96.6% to 100% among 116 patients and Ding et al [ 17 ] reported a 100% SVR rate among 108 patients with mixed infections who were treated with pan-genotypic DAAs. Our satisfactory result of the treatment includes not only mixed-genotype variants but also genotype-undetermined variants, which further disparages the requirement for stringent genotype determination to facilitate HCV elimination.…”

“…The 2020 EASL [ 14 ] and 2019 AASLD [ 15 , 16 ] treatment guidelines now suggest two main regimens for treatment-naïve patients, i.e., glecaprevir (300 mg)/pibrentasvir (120 mg) (GLE/PIB), and sofosbuvir (400 mg)/velpatasvir (100 mg) (SOF/VEL) with pan-genotypic antiviral activity to simplify the treatment algorithm. A minority of the patients may get infected with a mixed HCV genotype [ 17 , 18 , 19 ] or the HCV genotype that was undetermined by conventional polymerase chain reaction (PCR) techniques [ 20 , 21 ]. To date, there is a paucity of real-world data on the effectiveness and safety of pan-genotypic DAAs for patients with these two specific scenarios for HCV elimination [ 17 , 18 , 19 ].…”

“…A minority of the patients may get infected with a mixed HCV genotype [ 17 , 18 , 19 ] or the HCV genotype that was undetermined by conventional polymerase chain reaction (PCR) techniques [ 20 , 21 ]. To date, there is a paucity of real-world data on the effectiveness and safety of pan-genotypic DAAs for patients with these two specific scenarios for HCV elimination [ 17 , 18 , 19 ]. Thus, this study aimed to evaluate the real-world safety and efficacy of pan-genotypic DAA in patients with mixed-genotype or genotype-undetermined HCV from the five hospitals in the Changhua Christian Care System.…”