Abstract
The risk of hepatitis C virus (HCV) recurrence after direct-acting antiviral (DAA) treatment is <0.5%. However, the distinction between HCV RNA late relapse and reinfection still represents a challenge in virological diagnostics. The aim of this study was to employ next-generation sequencing (NGS) to investigate HCV RNA recurrence in patients achieving a sustained virologic response (SVR) at least six months post-treatment. NGS was performed on plasma samples from six HCV-positive patients (Pt1–6) treated with DAA. NGS of HCV NS5B was analyzed before treatment (T0), after HCV RNA rebound (T1), and, for Pt3, after a second rebound (T2). Reinfection was confirmed for Pt5, and for the first rebound observed in Pt3. Conversely, viral relapse was observed when comparing T0 and T1 for Pt6 and T1 and T2 for Pt3. Z-scores were calculated and used to predict whether HCV-positive patient samples at different time points belonged to the same quasispecies population. A low Z-score of <2.58 confirmed that viral quasispecies detected at T0 and T1 were closely related for both Pt1 and Pt2, while the Z-score for Pt4 was suggestive of possible reinfection. NGS data analyses indicate that the Z-score may be a useful parameter for distinguishing late relapse from reinfection.
Highlights
IntroductionHepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide [1,2,3]
next-generation sequencing (NGS) analyses of the hepatitis C virus (HCV) NS5B region were performed on 13 samples from six patients (Pt1–Pt6) collected at baseline and at the first available plasma sample with HCV RNA recurrence
The behavioral risks of these patients supported the idea of reinfection events: Pt3 was coinfected with human immunodeficiency virus (HIV), while Pt5 admitted to a risky sexual encounter and both patients were people who inject drugs (PWID)
Summary
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, with approximately 71 million chronically infected individuals worldwide [1,2,3]. Several phases have occurred in the history of antiviral therapy for the treatment of chronic HCV hepatitis. The first drug used in the treatment was interferon (IFN) with sustained virologic response (SVR) rates of less than 10%. In the late 1990s, ribavirin was combined with IFN, resulting in SVR rates of 35–40% in treated patients. An important turning point came with the introduction of pegylated interferon (peg-IFN) where SVR rates greater than 50% were achieved. The introduction of new direct-acting antivirals (DAAs) revolutionized HCV treatment, leading to the possibility of HCV elimination [4]
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