Review
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World J Gastroenterol. Nov 14, 2012; 18(42): 6060-6069
Published online Nov 14, 2012. doi: 10.3748/wjg.v18.i42.6060
Current progress in the treatment of chronic hepatitis C
Alexandra Alexopoulou, George V Papatheodoridis
Alexandra Alexopoulou, George V Papatheodoridis, 2nd Department of Internal Medicine, Athens University School of Medicine, Hippokration General Hospital of Athens, 115 27 Athens, Greece
Author contributions: Alexopoulou A performed the literature search and wrote the first draft of the manuscript; Papatheodoridis GV designed the manuscript and edited the final draft of the manuscript.
Correspondence to: George V Papatheodoridis, MD, 2nd Department of Internal Medicine, Athens University School of Medicine, Hippokration General Hospital of Athens, 114 Vas. Sophias Ave., 115 27 Athens, Greece. gepapath@med.uoa.gr
Telephone: +30-210-7774742 Fax: +30-210-7706871
Received: May 7, 2012
Revised: July 12, 2012
Accepted: August 14, 2012
Published online: November 14, 2012
Abstract

Over the last decade, the standard of care for the treatment of chronic hepatitis C has been the combination of pegylated-interferon-alfa (PEG-IFN) and ribavirin (RBV) which results 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 first-generation NS3/4A HCV protease inhibitors, have been recently licensed in several countries around the world to be used in combination with PEG-IFN 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-naïve 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 on-treatment virological response results in shortening of the total therapy duration to only 24 wk in 45%-55% of treatment-naïve 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 (anemia and dysgeusia for boceprevir; pruritus, rash and anemia for telaprevir), new drug interactions and increasing difficulties in compliance. Moreover, the SVR rates are still poor in very difficult to treat subgroups of genotype 1 patients, such as null responders with cirrhosis, while there is no benefit for patients who cannot tolerate PEG-IFN/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. Preliminary data suggest that the treatment of chronic HCV patients with well tolerated combinations of oral agents without PEG-IFN is feasible and may lead to a universal HCV cure over the next 5-10 years.

Keywords: Chronic hepatitis C; Pegylated interferon; Ribavirin; Protease inhibitors; Nucleos(t)ide analogue inhibitors; Non-nucleos(t)ide analogue inhibitors; Hepatitis C virus polymerase; NS5A inhibitors; Cyclophilin inhibitors