Selective serotonin reuptake inhibitors use and hepatocellular carcinoma in patients with alcohol use disorder

Background: Research has proposed that selective serotonin reuptake inhibitors (SSRIs) were associated with a reduction of the risk of hepatocellular carcinoma (HCC). The objective of this study is to investigate whether SSRIs use is associated with decreased risk of HCC in patients with alcohol use disorder (AUD). Patients and methods: We conducted a retrospective population-based cohort study using Taiwan's National Health Insurance Research Database (NHIRD) from 1997 to 2013 and enrolled patients with newly diagnosed AUD. After propensity scores matching at a ratio 1:4, total of 4945 SSRI users and 19,785 non-SSRI users were included in the matched cohort. Patients were followed up from the 365th day after the date of first exposure to SSRIs to occurrence of HCC, the date of death, or the end of 2013. Cox proportional hazard regressions were performed to evaluate hazard ratio (HRs) for HCC in SSRI-exposed patients compared with unexposed patients. Results: In the main study cohort, SSRI use was associated with significant lower risk of HCC compared to the non-SSRI users after adjusting for age, sex, income, urbanization, alcoholic fatty liver, alcoholic hepatitis and diabetes (adjusted hazard ratio [aHR] = 0.31, 95 % CI = 0.24−0.39). The negative association of SSRI use and HCC was replicated in the matched cohort (aHR = 0.58, 95 % CI = 0.44−0.77). The effect of SSRI use on HCC was dose-related in both cohorts (p for trend < 0.0001). Conclusions: This study showed that SSRIs use was associated with a reduction risk of HCC among AUD patients in a cumulative dose effect manner.