Advances in and the future of treatments for hepatitis C

Abstract

Enormous progress has been made in the understanding of the hepatitis C virus and the development of novel therapeutic agents since the identification of the virus 25 years ago. From initial interferon monotherapy providing only 6% viral clearance rate in the 1980s, pharmacotherapeutics has now entered an exciting new era with direct-acting antiviral agents demonstrating viral clearance rates of more than 70%. We are now at the beginning of an era where combinations of direct-acting antiviral agents may pave the way for interferon-free regimens, even improving the viral clearance rate to near 100%.

Keywords::

• boceprevir
• daclatasvir
• danoprevir
• deleobuvir
• direct-acting antiviral therapy
• faldaprevir
• hepatitis C
• protease inhibitors
• simeprevir
• sofosbuvir
• telaprevir

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current generation of protease inhibitors (PIs) still require pegylated interferon and ribavirin (PR) to achieve high sustained virological response (SVR) rates.

• Genetic polymorphisms in the hepatitis C virus, such as NS3 Q80K, significantly reduce the efficacy of some of the new PIs.

• For triple and quadruple therapies combining PIs with PR, studies have shown possible reduction of the duration of treatment from 24 to 12 weeks without affecting SVR rates.

• Cirrhotic patients with HCV genotype 3 infection remain challenging to treat, as novel therapies currently under investigation for this subgroup still have reduced efficacy and high virological relapse rates.

• Using PI-containing regimens to treat post-liver transplant HCV recurrence may increase the SVR rates from 20% (with standard PR therapy) to as high as 70%.

• Several sofosbuvir-containing interferon-free regimens with dual or triple direct-acting antivirals demonstrate 95–100% SVR12 rates for both treatment-naïve and treatment-experienced genotype 1 patients.

• The interferon-free combination of ABT-450 with ritonavir, ABT-267 and ABT-333 achieved near 100% SVR rates, which was not affected by the presence or absence of ribavirin.

Notes