Antivirals against HCV infection: the story thus far.

Ahmad Adebayo Irekeola,Engku Nur Syafirah Ear,Rafidah Hanim Shueb,Nur Amalin Zahirah Mohd Amin,Nazri Mustaffa

doi:10.3855/jidc.14485

Ahmad Adebayo Irekeola, Engku Nur Syafirah Ear + Show 3 more

Open Access

https://doi.org/10.3855/jidc.14485

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Abstract

Remarkable scientific breakthroughs have been made in the stride towards the development of potent and tolerable hepatitis C regimens within the last three decades. Earlier approaches involved the use of pegylated interferon alfa and ribavirin as standard-of-care treatment. Treating genotype 1a infection with this regimen which was at that time considered the gold standard for hepatitis C virus therapy was rife with challenges; safety and toxicity issues necessitated a rigorous quest for alternative regimens. Deeper understanding of the pathogenesis of hepatitis C virus ushered in the era of direct acting antiviral agents. These agents have been the subject of intensive research in the last two decades, leading to the development of drug classes such as protease inhibitors (e.g., grazoprevir), NS5A inhibitors (e.g., daclatasvir) and NS5B inhibitors (e.g., sofosbuvir). While many are still under development, several have been approved for hepatitis C therapy. A number of studies investigating the combination of direct acting antiviral agents with or without pegylated interferon and/or ribavirin for the treatment of chronic hepatitis have demonstrated sustained virologic response of > 90%. Given the array of direct acting antiviral agents currently available, the present landscape of hepatitis C therapy is now characterized by a gradual transition to all-oral interferon-free regimens. Despite these milestones, the WHO global target of eliminating hepatitis C as a public health problem by 2030 seems uncertain. In this review, we provide a concise account of the evolution and advancements in the development of anti-HCV regimens.

Highlights

Since its discovery in 1989 [1], hepatitis C virus (HCV), one of five viruses most implicated in viral hepatitis, has been extensively studied
Conclusions and future directions Given the absence of a licensed HCV vaccine, the use of anti-HCV agents and drugs has been the mainstay of hepatitis C therapy for many years
The emergence of Direct acting antiviral (DAA) has greatly revolutionized the terrain of HCV therapeutics; treatment durations have become shorter (8-12 weeks), drugs are more tolerable with minimal side effects, and sustained virological response (SVR) rates have increased to over 90% in most chronically infected HCV populations

Summary

Introduction

Since its discovery in 1989 [1], hepatitis C virus (HCV), one of five viruses most implicated in viral hepatitis, has been extensively studied. A study conducted in 1986 to investigate the effect of recombinant human IFN-α for the treatment of chronic non-A, non-B hepatitis showed that interferon could normalize serum aminotransferase levels and improve liver histology [8]. This foremost finding sparked, in large part, the race for anti-HCV therapy. Ribavirin had been available for medical use prior to the discovery of HCV [15] It is often used in combination with another regimen since its usage as monotherapy is not effective for the treatment of chronic hepatitis C infection [16]. 1986 Proof of concept – using recombinant human alfa interferon for the treatment of chronic non-A, non-B hepatitis in patients

2001 Introduction of pegylated interferon alfa

Findings

Conclusions and future directions