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Shimizu et al. Hepatoma Res 2020;6:12 I http://dx.doi.org/10.20517/2394-5079.2019.48 Page 3 of 9

Magnetic resonance examinations were performed in all patients using a 1.5 T scanner (Signa Excite HD;
GE Healthcare, USA). Gd-EOB-DTPA was used as a contrast agent. The contrast material was administered
as a bolus at a dose of 0.1 mL/kg body weight at a rate of 2 mL/s followed by flushing with 20 mL
saline solution using a power injector. Images of the arterial phase, portal venous phase, late phase, and
hepatobiliary phase (HPB) were obtained 18 s, 60 s, 150 s, and 20 min after the peak time, respectively, after
2
contrast injection. DWI was acquired before HPB with b values of 0 and 1000 s/mm . Apparent diffusion
2
coefficient (ADC) maps were obtained automatically by two images of b values of 0 and 1000 s/mm .
Dynamic CT scan with a section thickness of 2 mm was performed. For triple-phase dynamic CT scans,
arterial, portal, and equivalent phases were set at 35, 70, and 150 s, respectively, after injection of the
contrast agent. Board-certified radiologists diagnosed HCC based on typical patterns, such as an early-
phase hyperattenuation area and a late-phase hypoattenuation area on dynamic study. Pathologic diagnosis
was confirmed by a certified pathologist who was unaware of the patient’s clinical data.

RFA procedure
RFA was percutaneously performed by using local anesthesia. We used an internally water-cooled 17
G cooled-tip electrode with an impedance-controlled generator (Cosman generator, Cool-Tip System,
Radionics, Burlington, MA, USA). When the target nodule was more than 20 mm in diameter, multiple
needle insertions and multiple ablations of one nodule were performed.

Statistical analysis
All statistical analyses were performed using Easy R (EZR) version 3.4.1 (Saitama Medical Center, Jichi
[14]
Medical University, Saitama, Japan) , a graphical user interface for R (The R Foundation for Statistical
Computing, Vienna, Austria). P < 0.005 was considered statistically significant. Fisher’s exact test, paired t
test, and Mann-Whitney U test were adopted to determine the differences between the two indexes. Fisher’s
exact test was used to evaluate the intensity of DWI and T2WI. Survival curves were estimated using the
Kaplan-Meier method. Overall survival (OS) was defined as the period between the treatment date of HCC
and the patient’s death or last visit, and progression-free survival (PFS) was defined as the period between
the treatment date of HCC and the recurrence confirmation date of dynamic CT or EOB-MRI.

RESULTS
Comparison of demographics and laboratory data
The baseline clinical characteristics of all patients are shown in Table 1. Among them, 26 patients achieved
SVR with DAAs before HCC diagnosis (DAA-SVR HCC) and HCV RNA was detected in the remaining 80
patients (HCV-positive HCC). The median age of all patients was 75 years old and the median tumor size
was 18 (8-29) mm. Serum alanine aminotransferase (ALT; 18.5 vs. 53.0 IU/mL, P = 0.001) and α-fetoprotein
(AFP; 3.42 vs. 25.3, P < 0.001) were significantly lower in DAA-SVR HCC patients than in HCV-positive
HCC patients and the mean platelet count was higher in DAA-SVR HCC patients than in HCV-positive
3
3
HCC patients (149 × 10 /μL vs. 102 × 10 /μL, P = 0.009). There was no significant difference in age, tumor
size, tumor number, albumin, total bilirubin, and prothrombin time international normalized ratio between
DAA-SVR and HCV-positive HCC patients. The median value of Wisteria floribunda agglutinin-positive
Mac-2 binding protein (WFA ± M2BP) in 25 patients with DAA-SVR HCC was 1.48.

Imaging features
The imaging features are shown in Table 2. There was no difference between DAA-SVR and HCV-positive
HCC in terms of features of arterial phase, late phase, or HPB. In contrast, all DAA-SVR HCC was depicted
as high intensity on DWI, whereas only 67.5% HCV-positive HCC was found (P < 0.001). Moreover, high
intensity on T2WI was significantly higher in DAA-SVR HCC than in HCV-positive HCC (92.6% vs.
67.5%, P = 0.01). The typical imaging features of DAA-SVR HCC are shown in Figure 1. We also measured