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Page 2 of 10                                                  Iliescu et al. Hepatoma Res 2018;4:3  I  http://dx.doi.org/10.20517/2394-5079.2017.48

               evaluated by magnetic resonance imaging in order to detect the extension of the disease.

               Keywords: Hepatitis C virus, direct-acting antiviral therapy, hepatocellular carcinoma, trans-arterial chemoembolization


               INTRODUCTION
               Nowadays, hepatitis C virus (HCV) infection represents a global health problem, affecting over 160 million
               people worldwide . The progression of hepatitis C induced liver disease can be insidious, gradual, during
                              [1]
               several decades, leading to liver cirrhosis (LC) and hepatocellular carcinoma (HCC). It is estimated that,
               within 20 years of viral infection, about 20%-30% of subjects will develop LC . There is evidence that 2.8%-
                                                                                [2]
               11.7% of the patients with compensated LC will develop hepatic decompensation sooner or later; as for the
               incidence of HCC, a percentage of 1.8%-8.3% has been reported . The use of pegylated interferon (IFN) in
                                                                     [3]
               combination with ribavirin, in treating the HCV infection, leads to a sustained virological response (SVR)
               in about 50% of patients and it is known to have significant side effects .
                                                                           [4]
               Fortunately, recently there has been a much better understanding of the HCV particularities and structure.
               The efforts to improve the hepatitis C management resulted in the discovery and development of direct-
               acting antivirals (DAAs), which are meant to interfere with specific steps in HCV replication; in other
                                                                                                       [5]
               words, they directly interact with HCV encoded proteins, resulting in the disruption of viral replication .

               Therefore, DAAs have shown promising effects, increasing the rates of SVR to more than 90% with notably
               fewer side effects . Although the number of HCV-infected subjects is high, the access to the IFN-free
                              [6]
               therapy is still limited, due to increased costs and due to the fact that the HCV infection remains highly
               underdiagnosed . The use of nucleoside and protease inhibitors has relative contraindications in subjects
                             [7-9]
               diagnosed with end-stage renal disease.

               It is also worth mentioning that the IFN-free treatments are designed to cure the viral infection, but not
               the liver disease itself, once the HCV has led to LC or HCC. Furthermore, the risk of complications persists
               even after achieving SVR, although there is evidence demonstrating improvement in liver function tests
               after using DAAs [10,11] .


               Also, even after achieving SVR, re-infection is a possibility that can occur in 10%-15% of patients, especially
               in individuals at risk, such as intravenous drug users .
                                                            [12]

               This study aims to assess the effect of DAAs on liver function and to analyze the particularities of HCC
               diagnosed during or after treatment with Paritaprevir/Ombistasvir/Ritonavir and Dasabuvir with or without
               ribavirin (a treatment that is not recommended for patients with decompensated cirrhosis or liver cancer).



               METHODS
               In this study, we included a number of 278 patients, all of them infected with HCV genotype 1b, who received
               IFN-free treatment with Paritaprevir/Ombitasvir/Ritonavir and Dasabuvir, with or without Ribavirin, for
               12 weeks.

               An informed written consent was taken from all the participants and all their records were confidential. The
               scientific purpose of the study, as well as the implications of the therapy itself were presented in detail to
               each subject, as well as any unexpected research-related risk that may appear.

               Viral infection was assessed in each patient by quantitative HCV ribonucleic acid (RNA) tests, describing a
               high viral load in all patients, with more than 800,000 IU/L. In order to estimate the degree of fibrosis, each
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