Prior antiviral treatment and mortality among patients with hepatitis C virus-related hepatocellular carcinoma: A national cohort study

PLoS One. 2021 Aug 3;16(8):e0255624. doi: 10.1371/journal.pone.0255624. eCollection 2021.


Background: The current antiviral treatments available for hepatitis C virus (HCV) infection decrease the risk of hepatocellular carcinoma (HCC). Hence, patients with HCV infection who have not received antiviral treatment and have developed HCC may be those who missed timely antiviral treatment for HCV. However, the proportion of patients who missed timely antiviral treatment and its implications are largely unexplored.

Methods: A nationwide retrospective cohort of 4,592 newly diagnosed HCV-related HCC patients (2013-2017) was identified from the Korean National Health Insurance Service database. Prior antiviral treatment for HCV was defined as a history of at least one HCV-specific antiviral treatment before HCC diagnosis. The outcome was all-cause mortality.

Results: Prior antiviral treatment for HCV was identified in 802 (17.4%) patients, and 16%, 16%, 17%, 19%, and 19% of patients received antiviral treatment in the years 2013, 2014, 2015, 2016, and 2017, respectively (P = 0.21). During 8,085 person-years of follow-up (median, 1.4; maximum, 5.3 years of follow-up), 1,970 patients died. Mortality rates were lower in patients with prior antiviral treatment (15 deaths/100 person-years) than in those without prior antiviral treatment (27 deaths/100 person-years). The adjusted hazard ratio (95% confidence interval) for all-cause mortality on comparing patients who did and did not receive prior antiviral treatment was 0.68 (0.59, 0.79).

Conclusion: Timely antiviral treatment for HCV was suboptimal at the population level. Prior antiviral treatment for HCV reduced mortality rate in HCV-related HCC patients. Intensive HCV control strategies are needed to reduce the number of patients with HCV infection who miss timely HCV treatment.

MeSH terms

  • Aged
  • Antiviral Agents / administration & dosage*
  • Carcinoma, Hepatocellular / epidemiology
  • Carcinoma, Hepatocellular / mortality*
  • Carcinoma, Hepatocellular / virology
  • Female
  • Follow-Up Studies
  • Hepacivirus / drug effects*
  • Hepatitis C / complications*
  • Hepatitis C / drug therapy
  • Hepatitis C / virology
  • Humans
  • Liver Neoplasms / epidemiology
  • Liver Neoplasms / mortality*
  • Liver Neoplasms / virology
  • Male
  • Middle Aged
  • Prognosis
  • Republic of Korea
  • Retrospective Studies
  • Risk Factors
  • Survival Rate


  • Antiviral Agents

Grants and funding

The author(s) received no specific funding for this work.