Background: Using data from the National Health Insurance (NHI) of Taiwan, we conducted a nationwide population-based cohort study to investigate the association between antidepressant (ATD) use and the risk of hepatocellular carcinoma (HCC) in patients with hepatitis C virus (HCV) who had received interferon (IFN) therapy. Methods: This study included a total of 274,952 HCV-infected patients without hepatitis B virus infection who were enrolled in the NHI program between January 1, 1997 and December 31, 2013. Among these patients, only 10,713 (age ≥18 years) had received IFN therapy between 2004 and 2008. Among the patients who had received IFN therapy, 2014 had received ATDs, and 8684 had not. A Cox proportional hazards regression model was applied after adjusting for age, sex, income, urbanization, medical comorbidity, and medication use. Results: Compared with non-ATD-treated patients, ATD-treated patients were more likely to receive a diagnosis of alcohol-related disease, diabetes mellitus (DM), hypertension, and hyperlipidemia. ATD-treated patients had a significantly lower incidence of HCC than non-ATD-treated patients (P = 0.0019). Female, older (age ≥50 years), and non-DM patients who had received cumulative high doses of ATDs had a significantly lower risk of HCC than non-ATD-treated patients. After adjustment, only high-dose selective serotonin reuptake inhibitor (SSRI) use was inversely associated with HCC risk (adjusted hazard ratio 0.37, 95% confidence interval 0.19–0.71, P = 0.0027). Conclusions: Our study showed that ATD use, especially a relatively high cumulative dose of SSRIs, in HCV-infected patients who had received IFN was associated with reduced HCC risk. Future clinical studies are warranted to explore the underlying mechanisms and to apply them to newer direct-acting antiviral agent treatments.
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