Does interferon-free direct-acting antiviral therapy for hepatitis C after curative treatment for hepatocellular carcinoma lead to unexpected recurrences of HCC? A multicenter study by the Japanese Red Cross Hospital Liver Study Group

<div><p>Background and aim</p><p>This study aimed to elucidate whether interferon (IFN)-free direct-acting antiviral (DAA) therapy for hepatitis C after curative treatment of hepatocellular carcinoma (HCC) promotes HCC recurrence in a real-world large-scale cohort.</p><p>Methods</p><p>This multicenter study was conducted by the Japanese Red Cross Hospital Liver Study Group. This retrospective study analyzed 516 patients who underwent antiviral treatment for hepatitis C with either IFN (n = 148) or IFN-free DAA (n = 368) after curative HCC treatment; 78 IFN-treated patients and 347 IFN-free DAA-treated patients achieved sustained virological response (SVR). The recurrence rate of HCC was compared between the antiviral therapies. Logistic analysis and Cox proportional hazards analysis identified factors associated with early recurrence of HCC within 24 weeks of antiviral therapy and recurrence throughout the observation period, respectively.</p><p>Results</p><p>AFP at the completion of antiviral therapy, clinical stage of HCC, and non-SVR were independent factors associated with early recurrence of HCC. Among patients who had achieved SVR, the clinical stage of HCC and the level of AFP at completion of antiviral therapy were independent factors associated with early recurrence of HCC. For recurrence throughout the observation period in SVR patients, AFP at completion of antiviral therapy, duration between last HCC treatment to antiviral therapy, and the number of treatments were independent factors. There was no significant difference in the rate of early recurrence of HCC or recurrence throughout the observation period between IFN and IFN-free DAA treated patients.</p><p>Conclusions</p><p>There were no differences in the early recurrence rate of HCC between patients who underwent IFN and those who underwent IFN-free DAA as antiviral therapies.</p></div

Patient characteristics after propensity score matching.

<p>Patient characteristics after propensity score matching.</p

HCC cumulative recurrence rate after propensity score matching.

<p>Kaplan-Meier analysis performed after matching also revealed no significant difference between the IFN group (gray line) and the IFN-free DAA group (black line).</p

Factors associated with recurrence of HCC after completing antiviral therapy in patients who achieved SVR.

<p>Factors associated with recurrence of HCC after completing antiviral therapy in patients who achieved SVR.</p

Baseline patient characteristics.

<p>Baseline patient characteristics.</p

Cumulative hepatocellular carcinoma (HCC) recurrence rate in patients who achieved sustained virological response.

<p>Kaplan-Meier analysis does not show a significant difference between the IFN group (gray line) and IFN-free DAA group (black line).</p

Flow sheet summarizing study selection.

<p>Flow sheet summarizing study selection.</p

AUROC for items for which cutoff values were set in Table 4.

<p>AUROC for items for which cutoff values were set in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0194704#pone.0194704.t004" target="_blank">Table 4</a>.</p