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Page 4 of 9                                               Shimizu et al. Hepatoma Res 2020;6:12  I  http://dx.doi.org/10.20517/2394-5079.2019.48

               Table 1. Patients’ characteristics
                                                DAA-SVR HCC (n = 26)  HCV-positive HCC (n = 80)  P value
                Age (years), median (range)        75 (63-83)           75 (44-93)              0.27
                Sex (male/female)                  10/16                43/37                   0.26
                Number of tumors (single/multiple)  21/5                60/20                   0.61
                Tumor diameter (cm), median (range)  18.0 (10-29)       17.6 (8.0-29)           0.7
                BCLC stage A/B/C                   26/0/0               80/0/0                  1.0
                AFP (ng/mL)                        3.4 (2.0-6116.5)     25.3 (2.0-1660)         < 0.001
                PIVKA-II (mAU/mL)                  19.0 (12-94)         53.0 (13-245)           0.2
                Albumin (g/dL)                     4.0 (2.9-4.7)        3.7 (2.8-273)           0.6
                ALT (IU/mL)                        18.0 (12-94)         53 (13-245)             < 0.001
                       3
                Platelet (10 /μL)                  149 (45-189)         102 (33-344)            0.009
                Total bilirubin (mg/dL)            0.7 (0.3-2.0)        0.8 (0.3-2.6)           0.71
                PT%                                91 (57-113)          89 (31-120)             0.24
                Child-Pugh score 5/6               25/1                 68/12                   0.18
                Fib 4 index                        3.22(0.55-11.5)      6.01(1.66-25.2)         < 0.001
               BCLC: barcelona clinic liver cancer; AFP: alpha-fetoprotein; PIVKA-II: protein induced by vitamin K absence or antagonist-II; ALT: alanine
               aminotransferase; PT: prothrombin time; DAA: direct-acting antiviral; SVR: sustained viral response; HCC: hepatocellular carcinoma;
               HCV: hepatitis C virus

               Table 2. Image features of EOB-MRI at HCC diagnosis
                                       Early high     Late low      HBP low      T2WI high      DWI high
                DAA-SVR HCC (n = 26)  19/26 (73.0%)  24/26 (92.3%)  24/26 (92.3%)  24/26 (92.3%)  26/26 (100%)
                HCV-positive HCC (n = 80)  63/74 (85.1%)  74/74 (100%)  70/74 (94.6%)  54/80 (67.5%)  54/80 (67.5%)
               HBP: hepatobiliary phase; DWI: diffusion-weighted imaging; T2WI: T2-weighted imaging; DAA: direct-acting antiviral; SVR: sustained
               viral response; HCC: hepatocellular carcinoma; HCV: hepatitis C virus; EOB: ethoxybenzyl; MRI: magnetic resonance imaging

               the ADC values of HCC lesions on DWI; however, there was no significant difference between the two
               groups.

               Tumor biopsy was performed in 9 patients with DAA-SVR HCC and 33 patients with HCV-positive HCC.
               In nine patients with DAA-SVR HCC, four patients showed well-differentiated HCC and five patients
               were diagnosed with moderately or poorly differentiated HCC. In 33 patients with HCV-positive HCC,
               13 patients showed well-differentiated HCC and 20 patients were diagnosed with moderately or poorly
               differentiated HCC. There were significant associations with MRI and pathologic findings. HCC with high
               intensity on DWI or T2WI was more likely to have moderately or poorly differentiated HCC compared to
               well-differentiated HCC (DWI: 69.7% vs. 30.3%, P = 0.02; T2WI: 66.7% vs. 27.3%, P = 0.03).


               Prognosis after curative HCC treatment
               Among patients with DAA-SVR HCC, 1 patient received resection, 2 patients were treated by transcatheter
               arterial chemoembolization, 1 patient was not treated, and the remaining 22 patients were treated with
               RFA. All patients with HCV-positive HCC were treated with RFA. OS and PFS were not different between
               DAA-SVR and HCV-positive HCC [Figure 2].



               DISCUSSION
               The present study evaluated the imaging features of HCC that developed early after the eradication of
               HCV by DAA therapy. All of these HCC showed high intensity on MRI DWI and more than 90% showed
               high intensity on T2WI, which was significantly different from HCC with positive HCV RNA. The stage of
               HCC, such as the number of HCC nodules and the maximum diameter, was not different between these
               two groups, indicating that high intensity on DWI or T2WI on MRI is the characteristic imaging feature of
               HCC after DAA treatment.
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