Direct-Acting Antiviral Therapy Not Associated With Recurrence of Hepatocellular Carcinoma in a Multicenter North American Cohort Study

Amit G. Singal, Nicole E. Rich, Neil Mehta, Andrea Branch, Anjana Pillai, Maarouf Hoteit, Michael Volk, Mobolaji Odewole, Steven Scaglione, Jennifer Guy, Adnan Said, Jordan J. Feld, Binu V. John, Catherine Frenette, Parvez Mantry, Amol S. Rangnekar, Omobonike Oloruntoba, Michael Leise, Janice H. Jou, Kalyan Ram BhamidimarriLaura Kulik, Tram Tran, Hrishikesh Samant, Renumathy Dhanasekaran, Andres Duarte-Rojo, Reena Salgia, Sheila Eswaran, Prasun Jalal, Avegail Flores, Sanjaya K. Satapathy, Robert Wong, Annsa Huang, Suresh Misra, Myron Schwartz, Robert Mitrani, Sasank Nakka, Wassim Noureddine, Chanda Ho, Venkata R. Konjeti, Alexander Dao, Kevin Nelson, Kelly Delarosa, Usman Rahim, Meher Mavuram, Jesse J. Xie, Caitlin C. Murphy, Neehar D. Parikh

Research output: Contribution to journalArticlepeer-review

109 Scopus citations


Background & Aims: There is controversy over the effects of direct-acting antiviral (DAA) therapies for hepatitis C virus (HCV) infection on hepatocellular carcinoma (HCC) recurrence and tumor aggressiveness. We compared HCC recurrence patterns between DAA-treated and untreated HCV-infected patients who had achieved a complete response to HCC treatment in a North American cohort. Methods: We conducted a retrospective cohort study of patients with HCV-related HCC with a complete response to resection, local ablation, transarterial chemo- or radioembolization, or radiation therapy from January 2013 through December 2017 at 31 health systems throughout the United States and Canada. Cox regression was used to examine the association between DAA therapy and time to recurrence after a complete response, with DAA therapy analyzed as a time-varying exposure. We also estimated the association between DAA therapy and risk of early HCC recurrence (defined as 365 days after complete response). Results: Of 793 patients with HCV-associated HCC, 304 (38.3%) received DAA therapy and 489 (61.7%) were untreated. HCC recurred in 128 DAA-treated patients (42.1%; early recurrence in 52 patients) and 288 untreated patients (58.9%; early recurrence in 227 patients). DAA therapy was not associated with HCC recurrence (hazard ratio 0.90, 95% confidence interval 0.70–1.16) or early HCC recurrence (hazard ratio 0.96, 95% confidence interval 0.70–1.34) after we adjusted for study site, age, sex, Child-Pugh score, α-fetoprotein level, tumor burden, and HCC treatment modality. In DAA-treated and untreated patients, most recurrences were within the Milan criteria (74.2% vs 78.8%; P =.23). A larger proportion of DAA-treated than untreated patients received potentially curative HCC therapy for recurrent HCC (32.0% vs 24.6%) and achieved a complete or partial response (45.3% vs 41.0%) but this did not achieve statistical significance. Conclusion: In a large cohort of North American patients with complete response to HCC treatment, DAA therapy was not associated with increased overall or early HCC recurrence. HCC recurrence patterns, including treatment response, were similar in DAA-treated and untreated patients.

Original languageEnglish
Pages (from-to)1683-1692.e1
Issue number6
StatePublished - May 2019


  • Direct-Acting Antiviral
  • Hepatitis C Virus
  • Liver Cancer
  • Recurrence


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