Successful fourth line treatment of a relapse patient with chronic hepatitis C virus infection genotype 3a using sofosbuvir, glecaprevir/pibrentasvir, and ribavirin: a case report

Abstract

Background Relapses after therapy with direct-acting antiviral agents (DAA) in chronic hepatitis C virus (HCV) infections are rare due to high efficacy of interferon-free therapy regimens. The presence of resistance-associated substitutions (RAS) in proteins targeted by therapy can lead to lower rates of sustained virological response (SVR) in patients receiving DAA-therapy, and little evidence exists as to how to treat these patients. Case Summary We present a case of a multi-drug-resistant HCV-genotype-3a-infection in a 50-year-old female without confirmed cirrhosis but with advanced fibrosis (liver stiffness 11.6 kPa) and low viral load. Resistance testing revealed a Y93H mutation in the NS5A gene. Therapies using sofosbuvir and daclatasvir (1st), sofosbuvir, velpatasvir and ribavirin (2nd), and subsequently with sofosbuvir, velpatasvir, and voxilaprevir (3st) did not achieve SVR. Compliance was good with rapid negativity of HCV RNA at 4 weeks of treatment on all 3 occasions. No virological breakthrough was recorded with all regimens. As a rescue attempt, the patient received 24 weeks of sofosbuvir, glecaprevir/pibrentasvir, and weight-based ribavirin at 1000 mg. With this approach, she achieved SVR but developed hepatocellular carcinoma. Conclusion The combination of sofosbuvir, glecaprevir/pibrentasvir and ribavirin could be a rescue therapy after previous relapses on DAA-therapy, especially in patients with relapse after therapy with sofosbuvir, velpatasvir, and voxilaprevir.

Glecaprevir/pibrentasvir + sofosbuvir + ribavirin offers high cure rate for hepatitis C virus retreatment in real-world settings

“…1 Two case studies report SVR after 24 weeks of this regimen in 2 patients (HIV-coinfected genotype 1b, and genotype 3a), who had thrice-failed other DAA courses (the 3a patient had most recently failed sofosbuvir/velpatasvir/voxilaprevir). 5,6 One case report describes SVR after the on-treatment addition of sofosbuvir and ribavirin to glecaprevir/pibrentasvir in a treatmentnaïve genotype 3a patient. 7 Treatment of 23 glecaprevir/ pibrentasvir failures resulted in a 96% SVR rate after use of 12-16 weeks of this regimen as part of the MAGELLAN-3 phase IIIb clinical trial.…”

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure

“…So far, only case reports have been published on re-treatment in patients with failure on VOX/VEL/SOF rescue therapy, with the exception of one larger analysis. [44] , [45] , [46] This study, which included a subgroup of our cohort, reported high SVR rates for multiple targeted therapies with second-line DAAs such as VOX/VEL/SOF or G/P+SOF. 44 Rescue treatments in our study included G/P+SOF with or without RBV for 12-24 weeks and VEL/SOF plus RBV for 24 weeks in two patients with decompensated cirrhosis.…”

“…Consistent with previous reports, treatment response to rescue therapy with G/P+SOF with and without RBV for 12 to 24 weeks was observed to be excellent with SVR12 rates of 100%. 22 , 45 , 46 These results pose the question of whether G/P+SOF may be a more effective treatment option than VOX/VEL/SOF. In fact, G/P+SOF it is not only proposed as a third-line but also as a second-line treatment option in patients with difficult-treat cofactors by the international guidelines of AASLD and EASL.…”

Glecaprevir/pibrentasvir in combination with ribavirin as salvage therapy in chronic hepatitis C

“…Se realizó una búsqueda bibliográfica donde se encontraron series de casos pacientes con fallo a SOF/VEL/VOX que precisaron tratamiento de rescate ( Tabla 1 ). Los antivirales empleados fueron glecaprevir/pibrentasvir (GLE/PIB) junto con RBV, GLE/PIB + SOF + RBV, SOF/VEL/VOX + RBV y SOF/ VEL + RBV [ 2 - 6 ]. Tras comprobar que no había interacciones significativas entre el tratamiento antiviral y su medicación habitual (omeprazol, risperidona, diazepam y desvenlafaxina), finalmente se prescribió GLE/PIB y RBV 600 mg cada 12 horas durante 16 semanas, duración recomendada en pacientes con genotipo 3 pretratados.…”