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Page 6 of 12                                           Rutledge et al. Hepatoma Res 2019;5:31  I  http://dx.doi.org/10.20517/2394-5079.2019.19


























               Figure 2. Rates of de novo HCC by treatment group and SVR status. Colored bars represent rates of de novo HCC by SVR status, with
               95%CIs depicted by the capped 95%CI vertical black lines. Rates of de novo HCC were as follows: DAA group, overall: 2.01/100py (95%CI:
               1.38, 2.67), SVR: 3.57/100py (95%CI: 1.63, 5.88) and non-SVR: 9.83/100py (: 3.77,16.22). IFN group, overall: 1.45/100py (95%CI: 0.98,
               1.94), SVR: 0.70/100py, (95%CI: 0.41, 1.04), non-SVR: 2.94/100py (95%CI: 1.88, 4.04). Untreated group: 4.41/100py (95%CI: 2.10, 6.90).
               SVR: sustained viral response; IFN: interferon; DAA: direct-acting antiviral; CI: confidence interval; HCC: hepatocellular carcinoma

                        de nove
                Study Name
                Kobayashi et al.
                lnnes et al.
                loannou et al.
                Li et al.
                Miyase et al.







               Figure 3. Adjusted hazards ratio of risk of de novo HCC in DAA- vs. IFN-treated populations. The multivariate-adjusted hazard ratio
               of each individual study is represented by the blue square with the size of the square being proportional to the n of the study. The thin
               horizontal grey bars represent the 95%CI of each study and the thick vertical blue line marks where the HR is equal to 1. The red diamond
               with the dashed vertical red line is the overall adjusted HR, which was 0.58 (95%CI: 0.20, 1.07) for de novo HCC in the DAA population
               compared to the IFN-treated population. HCC: hepatocellular carcinoma; IFN: interferon; CI: confidence interval

               Rates of recurrent HCC
               The recurrence rate of HCC was relatively high across all groups: 16.76/100py (95%CI: 10.75, 22.91) and
               14.31/100py (95%CI: 10.17, 19.16) in DAA- and IFN-treated populations respectively. It was similar between
               untreated patients and IFN-treated patients without SVR [25.69/100py (95%CI: 14.44,37.27) compared to
               16.89/100py (95%CI: 10.05, 24.02)], suggesting that IFN does not have significant anti-tumor effect in the
               absence of viral clearance. Patients treated with DAA who did not achieve SVR appeared to have a high
               rate of recurrent HCC; however, the numbers of patients with DAA failure were small, thus the CI is
               wide: 44.16/100py, (95%CI = 0.006, 90.35). DAA-treated patients who achieved SVR had a recurrence rate
               of 18.17/100py (95%CI: 3.84, 33.58) and in IFN-treated populations with SVR the recurrence rate was not
               significantly different at 11.01/100py (95%CI: 4.85, 17.63) [Figure 4].


               When HCC recurrence that occurred during the first six months post-completion of treatment was
               excluded, the rates were similar between DAA and IFN groups: 10.75/100py, (95%CI: 5.50, 16.30) vs.
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