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Nakamura et al. Hepatoma Res 2019;5:16 I http://dx.doi.org/10.20517/2394-5079.2019.06 Page 5 of 11

Table 2. Characteristics of hepatocellular carcinoma before direct-acting antiviral treatment

Final HCC Tx before DAA
Characteristics All patients (n = 312)
Hepatectomy (n = 89) RFA (n = 223)
At the first HCC Tx
Max tumor diameter (mm)* 18 (14-25) 22 (16-30) 16 (13-22)
Tumor number (1/2/≥ 3)** 244 (78.2%)/42 73 (82.0%)/14 (15.7%)/2 171 (76.7%)/28
(13.5%)/26 (8.3%) (2.3%) (12.6%)/24 (10.7%)
AFP (ng/mL) 14.8 (7.2-57.4) 19.4 (8.1-99.3) 13.7 (6.8-52.1)
DCP (mAU/mL) 24.5 (17-56.8) 25 (16-142) 24 (17-48)
AFP-L3 (%) 4.3 (0-7.3) 6.4 (0-15.8) 4.3 (0-6.6)
At the final HCC Tx before DAA
Max tumor diameter (mm)* 15 (12-21.3) 22 (15.5-30) 15 (11-20)
Tumor number (1/2/≥ 3)** 246 (78.8%)/43 74 (83.1%)/13 (14.6%)/2(2.3%) 172 (77.1%)/30
(13.8%)/23 (7.4%) (13.5%)/21 (9.4%)
At the initiation of DAA
History of HCC Tx (1/2/≥ 3)* 190 (60.9%)/62 82 (92.1%)/6 (6.7%)/1 (1.1%) 108 (48.4%)/56
(19.9%)/60 (19.2%) (25.1%)/59 (26.5%)
The period from the final HCC Tx (days)* 297 (117-96) 495 (209-1101) 233 (104-544)
AFP (ng/mL)* 8.4 (4.9-16.9) 7.5 (4.1-11.4) 9.1 (5.1-23.6)
DCP (mAU/mL)** 16.5 (12-23) 15 (11-19) 18 (12-25)
AFP-L3 (%)** 3.5 (0-5.6) 0 (0-4.6) 3.8 (0-5.8)
After DAA Therapy
AFP (ng/mL)** 5.3 (3.3-7.7) 4.8 (3.1-6.7) 5.5 (3.4-8.5)
DCP (mAU/mL)* 17 (13-23) 15 (12-20) 18 (14-24.8)
AFP-L3 (%)** 0 (0-2) 0 (0-0) 0 (0-3.2)

*P < 0.001; **P < 0 .05; The values indicate the median (interquartile range) unless otherwise noted; AFP: alpha-fetoprotein; DCP:
des-gamma-carboxy prothrombin; AFP-L3: lens culinaris agglutinin-reactive alpha-fetoprotein; HCC: hepatocellular carcinoma; Tx:
treatment; DAA: direct-acting antiviral

Figure 2. The overall survival in patients treated with DAAs after curative treatment for HCC. The survival rates at 1, 2 and 3 years were
99%, 98% and 95%, respectively. HCC: hepatocellular carcinoma; DAA: direct-acting antiviral

1-, 2- and 3-year cumulative recurrence rates after DAA therapy were 11.4%, 31.6% and 49.4% in patients with
1 previous treatment; 25.1%, 45.3% and 57.5% in patients with 2-4 previous treatments; and 47.6%, 70.9% and 100%
in patients with more than 4 previous treatments, respectively.

Patterns of recurrence
The patterns of HCC recurrence after DAA therapy are shown in [Table 5]. The median diameter of the tumors
was 13 mm, and 44 patients (32.6%) had multiple tumors, including 3 patients (2.2%) with extrahepatic metastasis.
Two patients (1.5%) had rapidly progressing tumors: 1 had massive infiltrative-growing tumors with invasion to the