HCV; the Rising Concerns and Growing Hopes Figure 1. High Cirrhosis Risk Score (CRS) May Streamline Towards Treat- ment Before Liver Biopsy Cirrhosis Risk Score High Risk Treat Low Risk & Unclassiﬁable Liver Biopsy Stage 0- 1 Stage 2- 4 Low risk Indeterminate Delay treat Individualize Treat Gressner OA, Weiskirchen R, Gressner AM, Biomarkers of hepatic fibrosis, fibrogenesis and genetic pre-disposition pending between fiction and re- ality, Journal of Cellular and Molecular Medicine, John Wiley & Sons Ltd, with permission treatment commencement for such rapidly progressive patients should be re-emphasized. Among non-invasive tests of the same line, there are currently serum tests available which can use blood chemistry as surrogates in defining level of fibrosis. Wide application of these tests must depend on careful evaluation of their validity and reliability in the real practice (10). Alavian SM et al. 2.5. Treatments of HCV Infection Treatment regimens for chronic hepatitis C (CHC) have progressed within the past decade. The current standard of care which is the combination therapy of pegylated inter- feron alpha (PegIFNα) and ribavirin (RBV), has significantly improved sustained virological response (SVR) rates. There are some indicators which define and predict the response rate. The cardinal response predicting factors are GT (GT1 versus GT2 and GT3), baseline viral load (high versus low viral load in all genotypes), advanced fibrosis level (stage 3 and 4 versus stage 1 or 2) and cirrhosis. Figure 2 demon- strates how SVR achievement rate could vary in different prognostic profile patients (11-16) (Figure 2). 2.6. Growing Hopes for Eradication There are two recent FDA approved agents which are available worldwide (Boceprevir and Teleprevir). Both agents belong to the first generation HCV non-structural (NS) 3/4A protease inhibitors. Availability of these agents, which have been added to the current standard of care (SOC) for specific patients, has offered a new treatment option for patients infected with HCV, who are GT 1 and have been non-responder or have relapsed to previous therapies. The comparison between the current SOC and soon available direct antivirals as protease inhibitors, namely Boceprevir and Teleprevir shows that in previ- ously non-responders to SOC, addition of protease inhibi- tors (PIs) may increase SVR rate from 17-21% to 59-66% that roughly means three times more than previous response rates (17). The triple therapy regimen is now available in US and Canada and is expected to be reachable in the Mid- dle East including Iran in 2012. We should remain con- 60 50 40 20 10 0 ,% 30 R V S High Viral Load (all Genotypes) Advanced Fibrosis and cirhosis (stages 3 and 4) ITT Populations HCV Genotype 1 HIV/HCV HIV/HCV Genotype 1 AA Genotype 1 Figure 2. SVR Rates in HCV Infected Populations / Response Predictive Variables Hepat Mon. 2012 425