What does the pharmacological future of treating chronic hepatitis C look like?

Abstract

Development of direct acting antivirals has revolutionized the standard of care for the treatment of hepatitis C virus. New interferon-free regimens provide sustained virologic response rates of >90% in many genotype 1 patients with only 12 weeks of oral therapy. This review will provide a brief overview of current standards of care with a summary of the evidence supporting the recommended combinations of direct acting antivirals. We will discuss the direction of future therapies, with strategies for shorter durations of therapy and new all-oral combinations in the pipeline.

Keywords:

• direct acting antivirals
• hepatitis C virus
• interferon-free regimens
• ledipasvir
• sofosbuvir

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

• The future direction of hepatitis C (HCV) therapy is mostly likely to be the global adoption of IFN-free, direct acting antivirals (DAA)-based therapy with pangenotypic activity effective for all patient populations including those with challenging characteristics (renal failure, decompensated cirrhosis and postliver transplant).

• Combinations including novel DAAs have demonstrated high efficacy with short durations of therapy and raise the possibility of reducing durations even further. Future studies to further delineate patient characteristics that correlate with success with short duration therapy may be of great clinical benefit.

• Patients with HIV-HCV coinfection can achieve SVR12 rates comparable with HCV monoinfected patients.

• Currently available regimens (Table 1) have demonstrated high efficacy for genotype 1 (GT1) and 4 in Phase II & III clinical trials. There remains, however, a paucity of data for GT5 and 6.

• Currently approved regimens in the USA are suboptimal for the treatment of GT3, especially for HCV treatment experienced patients with cirrhosis. We await ‘real-world’ data regarding the efficacy of sofosbuvir/DCV (available outside of the USA) with this patient population. Novel DAA combination grazoprevir and elbasvir show promise for this group.

• Further studies are needed to guide optimal regimens and timing of treatment for patients with decompensated liver disease. Results of SOLAR-1 with sofosbuvir/ledipasvir/ribavirin suggest that treatment prior to advancement to decompensated liver disease is needed for optimal outcomes.

• Patients with severe renal disease continue to have limited treatment options. We await safety and efficacy data for sofosbuvir, and for PrOD. Grazoprevir/elbasvir has been demonstrated to be effective in this patient population.

• Further studies to guide the optimal use and dosing of ribavirin are needed.

Notes