Hydroxychloroquine Reduced the Risk of Hepatocellular Carcinoma in Patients with Hepatitis C Virus infection: A Retrospective Cohort Study

Abstract Purpose Hydroxychloroquine (HCQ) exerts anticancer effects through anti-inflammatory, autophagy-related, and non-autophagy-related mechanisms. This study investigated the association between HCQ use and risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection. Methods We enrolled patients with HCV infection from Taiwan’s National Health Insurance Research Database, covering the period from January 1, 2006, to December 31, 2016. Kaplan–Meier analysis and Cox proportional hazards regression were used to analyze the HCC risk in HCQ users and non-users. We evaluated the association between HCC risk, concurrent medication use, and comorbidities. Results We included 139,263 patients with a newly diagnosed HCV infection. During the follow-up period, 1037 patients developed HCC. In the HCQ user group (n = 1598), 62 patients had HCC, whereas 975 of the 15,980 HCQ non-users developed HCC. Patients with chronic HCV infection who used HCQ had a significantly lower risk of HCC than those who did not (adjusted hazard ratio [aHR], 0.68; 95% Confidence interval [CI], 0.51–0.92). No dose–response relationship was observed between the HCQ user and non-user groups. The use of concurrent medications, such as antihistamines (aHR, 0.74; 95% CI, 0.59–0.93), statins (aHR, 0.38; 95% CI, 0.32–0.46), nonsteroidal anti-inflammatory drugs (aHR, 0.60; 95% CI, 0.48–0.76), and aspirin (aHR, 0.82; 95% CI, 0.72–0.94), was associated with a lower risk of HCC. Conclusion HCQ use may reduce the risk of HCC in patients with HCV infection. These results provide key insights into the potential benefits of HCQ use in preventing HCC in patients with chronic HCV infection.