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End of the story: direct-acting antiviral agents are not associated with recurrence of hepatocellular carcinoma
  1. Ruben Hernaez1,2,3,
  2. Robert Thimme4
  1. 1Gastroenterology and Hepatology, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  2. 2Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
  3. 3Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
  4. 4Department of Medicine II, Gastroenterology, Hepatology, Endocrinology and Infectious Diseases, Medical Center, University of Freiburg, Freiburg, Germany
  1. Correspondence to Dr Ruben Hernaez, Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA; ruben.hernaez{at}

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The association between direct-acting antiviral (DAA) therapy and hepatocellular carcinoma (HCC) risk and recurrence was initially introduced by Reig et al.1 In their study, they followed up 58 patients with HCC who had sustained virological response for a median of 5.7 months, 16 had a recurrence of HCC while 42 did not, which raised concerns on the safety of hepatitis C therapy in patients with HCC. Several other studies did not show such association or improved survival.2 3 In 2019, the American Gastroenterological Association provided an expert review4 that stated that “there are no conclusive data that DAA therapy is associated with increased or decreased risk, differential time to recurrence, or aggressiveness of recurrent HCC in patients with complete response to HCC therapy”.

The study by Drs Sapena, Enea, Torres, Celsa et al aimed to shed light on this controversy by conducting a massive effort to complete an individual participant data meta-analysis (IPD-MA).5 The authors assessed the recurrence rate of HCC in 977 DAA-treated patients after a complete response from 12 retrospective and 9 prospective studies. The recurrence rate and death risk per 100 person-years (PY) in DAA-treated patients were 20 (95% CI 13.9 to 29.8, I2 for statistical heterogeneity=74.6%) and …

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  • Contributors Both authors contributed equally in the design, writing and final approval of the Commentary.

  • Funding RH is also supported by the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413), Michael E. DeBakey VA Medical Center, Houston, Texas, USA.

  • Disclaimer The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.

  • Competing interests None declared.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting or dissemination plans of this research.

  • Provenance and peer review Commissioned; internally peer reviewed.

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