Letter to the editor: Successful treatment of multidrug-resistant hepatis C after >12 months of continuous therapy with direct-acting antivirals.

Abstract

To the editor, We read the study by Trudeau et al., which presented a patient case with a history of multiple failed treatments who ultimately achieved sustained virological response (SVR) after an extended course of direct‐acting antiviral (DAA) regimens.1 However, we have some concerns about this conclusion. First, patients with hepatitis C virus (HCV) and cirrhosis may be subject to more medical and lifestyle monitoring after initial diagnosis and are vulnerable to many confounding factors. Recent study showed that common drug–drug interactions exist in glecaprevir–pibrentasvir (GLE‐PIB) or sofosbuvir–velpatasvir (SOF‐VEL) such as proton‐pump inhibitors, histamine‐2 receptor antagonists, and lipid‐lowering agents, which will affect the efficacy of GLE‐PIB or SOF‐VEL.2 In this study, no clear statement about the medical monitoring was shown. Moreover, interferon‐based combination regimes for patients with liver cirrhosis may have a higher risk of treatment‐associated serious adverse events.3 This study just regarded SVR as an important treatment outcome of the patient with HCV. However, the safety evaluation and complication after extended DAA therapies were not mentioned in the study. Secondly, the volatile regimens through the treatment process makes readers confused, and no evidence supports it. For example, at week 4 posttreatment initiation, the patient had an undetectable viral RNA level and remained negative for the duration of treatment, but the therapy was immediately changed to SOF‐VEL at week 12 for no powerful reason. Moreover, the previously “failed” treatment regime have many common drugs with the current treatment regime, which cannot exclude the possibly subsequent and positive impact of previous treatments on patients. Thirdly, the patient contracted coronavirus disease 19 (COVID‐19) during this course of therapy, which severely influences the antiviral and survival outcome. A multicenter cohort study showed that there is a close association between chronic HCV and COVID‐19.4 The mechanism of liver dysfunction in patients with COVID‐19 includes direct cytopathic effects, immune reaction and cytokine storm‐related multiorgan failure, hypoxia‐reperfusion dysfunction, and drug‐induced liver injury because of the various drugs used for COVID‐19 treatment.5 The treatment outcomes of the patient with HCV may be affected by the influence of COVID‐19 or the cotreatment of COVID‐19. In conclusion, whether extending treatment necessary to successfully induce a durable response among patients with previous treatment failures remains unclear.