Review article
Novel Therapies in the Treatment of Chronic Hepatitis C Infection
Davor Radić
; KBC Zagreb
Marina Premužić
; KBC Zagreb
Ivana Knežević Štromar
; KBC Zagreb
Rajko Ostojić
; KBC Zagreb
Abstract
Over the last 15 years, the standard therapy for the treatment of chronic hepatitis C (HCV) has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin (RBV) administered for 24 to 48 weeks depending on the HCV genotype. Standard therapy resulted in sustained virological response (SVR) rates of 75%-85% in patients with genotypes 2 or 3 but only of 40%-50% in patients with genotype 1. Currently, there are rapid and continuous developments of numerous new agents against hepatitis C virus (HCV), which are the focus of this review. Boceprevir and telaprevir, two firstgeneration NS3/4A HCV protease inhibitors, have revolutionized HCV therapy. They have been recently licensed in several countries around the world to be used in combination with PEGIFN and RBV for the treatment of genotype 1 patients. Boceprevir or telaprevir based triple regimens, compared with the PEG-IFN/RBV combination, improve the SVR rates by 25%-31% in treatment-naive genotype 1 patients, by 40%-64% in prior relapsers, by 33%-45% in prior partial responders and by 24%- 28% in prior null responders. At the same time, the application of response-guided treatment algorithms according to the ontreatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-naive patients. There are, however, several challenges with the use of the new triple combinations in genotype 1 patients, such as the need for immediate results of HCV RNA testing using sensitive quantitative assays, new and more frequent adverse events (anaemia and dysgeusia for boceprevir; pruritus, rash and anaemia for telaprevir), new drug interactions and increasing difficulties in compliance. However, the SVR rates are still poor in subgroups of genotype 1 patients, which are very difficult to treat, such as null responders with cirrhosis. There is no benefit for patients who cannot tolerate PEGIFN/ RBV or who are infected with non-1 HCV genotype. Many newer anti-HCV agents of different classes and numerous combinations are currently under evaluation with encouraging results. New DAA with simplified dosing regimens and/or minimal toxicity which, when used in combination, will lead to viral eradication in almost all CHC patients who undergo treatment are expected in the years ahead. The novel agents in clinical development are paving the way for future interferon-sparing regimens.
Keywords
hepatitis C; individualized treatment; HCV genotype; new antiviral drugs
Hrčak ID:
102973
URI
Publication date:
18.4.2013.
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