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Page 2 of 9                                               Shimizu et al. Hepatoma Res 2020;6:12  I  http://dx.doi.org/10.20517/2394-5079.2019.48

               Conclusion: High intensity on DWI and hyperintensity on T2WI were distinctive features of HCC that developed
               within one year after the end of DAA treatment.


               Keywords: Hepatocellular carcinoma, direct-acting antivirals, sustained viral response, contrast enhanced magnetic
               resonance imaging



               INTRODUCTION
                                                                              [1]
               Hepatocellular carcinoma (HCC) is one of the most common cancer types  and the major cause of cancer-
                           [2]
                                                                                                        [3]
               related deaths . Chronic liver disease and cirrhosis are closely associated with the development of HCC .
               In patients with chronic hepatitis C virus (HCV) infection, sustained viral response (SVR) can be observed
                                                                                             [4]
               in more than 90% of the cases by antiviral therapy using direct-acting antivirals (DAAs) . However, it
               remains controversial whether HCC that developed after the eradication of HCV with DAA regimens
               differs from those that developed during active infection with HCV. Although the incidence of HCC
                                                                                            [5]
               development may not be suppressed or enhanced by the eradication of HCV with DAA , the question
               remains whether there are differences in the biological characteristics, such as histology or radiologic
               findings, or the clinical course after curative treatment. Imaging features of HCC after SVR with DAA have
               not been studied in detail.


               For the diagnosis of HCC, contrast-enhanced magnetic resonance imaging (MRI) using gadolinium
               ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) is often used [6-9] . MRI has an
               advantage over computer tomography (CT) in that various images, including diffusion-weighted images
               (DWI) or T2-weighted images (T2WI), can be obtained in addition to the vascularity information of HCC
               nodules. DWI is imaging associated with the restriction of water molecule movement and reflects the
               histopathologic features of organs and tissues by virtue of high scan speed. It is widely known that DWI
               is valuable for the diagnosis and differential diagnosis of neoplasm in the liver, including small (< 2 cm)
                    [10]
               HCC . In this study, we evaluated the MRI features of HCC that developed within one year after the end
               of DAA treatment.


               METHODS
               Patients
               In our hospital cohort, 695 patients with chronic hepatitis C were treated with DAA regimens and achieved
               SVR between October 2014 and September 2016. At baseline and after SVR, the surveillance for HCC
               was performed using ultrasonography, contrast-enhanced CT, or EOB-MRI. Among these 695 patients,
               26 patients developed HCC within one year after the end of DAA therapy (DAA-SVR HCC). All of these
               patients had no previous history of HCC treatment. For comparison, 80 HCC patients with positive HCV
               RNA (HCV-positive HCC) were selected from 208 consecutive HCC patients with HCV infection who
               were treated for the first time from December 2011 and February 2018 according to the following inclusion
               criteria: (1) HCV RNA positive at the time of HCC diagnosis; (2) Child-Pugh A; (3) tumor diameter ≤ 3 cm
               and number of nodules ≤ 3; (4) no vascular invasion and no extrahepatic metastasis; (5) EOB-MRI
               available; and (6) radiofrequency ablation (RFA) was performed. This study was conducted according to
               the ethical principles of the Declaration of Helsinki and STROBE guidelines. This study was approved by
               the Ethics Committees of Musashino Red Cross Hospital (approval number 28077).

               HCC diagnosis
                                                                                 [11]
               The radiologic diagnosis for HCC was based on the Japan Society of Hepatology , the American Association
                                                                                              [13]
                                         [12]
               for the Study of Liver Disease , and the European Association for the Study of the Liver  guidelines.
               Typical radiographic findings on dynamic study (CT or MRI) or needle biopsy were used for diagnosis.
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