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. 2020;59(7):901-907.
doi: 10.2169/internalmedicine.3382-19. Epub 2020 Apr 1.

Influence of Interferon-free Direct-acting Antiviral Therapy on Primary Hepatocellular Carcinoma Recurrence: A Landmark Time Analysis and Time-dependent Extended Cox Proportional Hazards Model Analysis

Satoshi Miuma  1 , Junya Miyamoto  2 , Naota Taura  1 , Masanori Fukushima  1 , Ryu Sasaki  1 , Masafumi Haraguchi  1 , Hidetaka Shibata  1 , Shuntaro Sato  2 , Hisamitsu Miyaaki  1 , Kazuhiko Nakao  1
Affiliations

Influence of Interferon-free Direct-acting Antiviral Therapy on Primary Hepatocellular Carcinoma Recurrence: A Landmark Time Analysis and Time-dependent Extended Cox Proportional Hazards Model Analysis

Satoshi Miuma et al. Intern Med. 2020.

Abstract

Objective The influence of interferon (IFN)-free direct-acting antiviral (DAA) on hepatocellular carcinoma (HCC) recurrence remains unclear. Previous retrospective analyses revealed that the time interval between HCC curative treatment and IFN-free DAA induction is the critical factor affecting HCC recurrence. Thus, this study aimed to examine the influence of DAA therapy on HCC recurrence considering this interval. Methods Factors contributing to HCC recurrence were retrospectively analyzed using a landmark time analysis and time-dependent extended Cox proportional hazards model. Patients After screening 620 patients who were diagnosed with primary HCC from January 2001 to December 2016, 76 patients with early-stage (primary and solitary) disease who received curative treatment and were positive for serum hepatitis C virus RNA were included. Results HCC recurrence was observed in 8 of 17 (47.1%) patients who had received IFN-free DAA therapy and 45 of 59 (76.3%) who had not. No significant difference was seen between the IFN-free DAA (-) and IFN-free DAA (+) groups in the landmark time and time-dependent Cox proportional hazards model analyses. However, IFN-free DAA therapy tended to decrease the HCC recurrence rate after curative treatment for primary HCC in patients with chronic hepatitis. In addition, IFN-free DAA therapy tended to decrease the second HCC recurrence rate after treatment for the first HCC recurrence. Conclusion Our results, with a consideration of the time interval between HCC curative treatment and IFN-free DAA induction, showed that IFN-free DAA therapy was not associated with early-stage HCC recurrence after curative treatment.

Keywords: direct-acting antivirals; hepatitis C; hepatocellular carcinoma; recurrence; time interval.

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Conflict of interest statement

The authors state that they have no Conflict of Interest (COI).

Figures

Figure 1.
Figure 1.
Flowchart illustrating the method of screening patients for the present study.
Figure 2.
Figure 2.
Cumulative HCC recurrence rate after curative treatment for primary and solitary HCC in the presence or absence of IFN-free DAA therapy (landmark time analysis). The HCC recurrence rate in patients who had received IFN-free DAA therapy [IFN-free DAA (+), bold line] or had not [IFN-free DAA (-), thin line] was analyzed by a landmark time analysis set at 1 year (A) and 2 years (B). HCC: hepatocellular carcinoma, IFN-free DAA: interferon-free direct-acting antiviral therapy
Figure 3.
Figure 3.
Subgroup analyses of the influence of IFN-free DAA therapy on recurrence after curative treatment. Subgroup analyses of the hazard ratio of the influence of IFN-free DAA therapy on HCC recurrence by a time-dependent extended Cox proportional hazards model. HCC: hepatocellular carcinoma, IFN-free DAA: interferon-free direct-acting antiviral therapy
Figure 4.
Figure 4.
Cumulative second HCC recurrence rate after treatment for the first HCC recurrence in the presence or absence of IFN-free DAA therapy. The cumulative second HCC recurrence rate after treatment for the first HCC recurrence was analyzed by a Kaplan-Meier analysis (A) in all patients with a first HCC recurrence (n=25) and (B) in the patients who had received curative treatment for the first HCC recurrence (n=17). The patients who received IFN-free DAA therapy [IFN-free DAA (+) group] are represented as a bold line, and those who had not received [IFN-free DAA (-) group] are presented as a thin line. HCC: hepatocellular carcinoma, IFN-free DAA: interferon-free direct-acting antiviral therapy
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References

    1. Saab S, Le L, Saggi S, Sundaram V, Tong MJ. Toward the elimination of hepatitis C in the United States. Hepatology 67: 2449-2459, 2018. - PubMed
    1. Flisiak R, Pogorzelska J, Flisiak-Jackiewicz M. Hepatitis C: efficacy and safety in real life. Liver Int 37 (Suppl): 26-32, 2017. - PubMed
    1. Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 127: S35-S50, 2004. - PubMed
    1. El-Serag HB. Hepatocellular carcinoma and hepatitis C in the United States. Hepatology 36: S74-S83, 2002. - PubMed
    1. Bartosch B, Thimme R, Blum HE, Zoulim F. Hepatitis C virus-induced hepatocarcinogenesis. J Hepatol 51: 810-820, 2009. - PubMed

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