Akshaya Srikanth Bhagavathula1, Benjamin Woolf2, Jamal Rahmani3, Kota Vidyasagar4, Wubshet Tesfaye5,6. 1. Department of Social and Clinical Pharmacy, Faculty of Pharmacy at Hradec Kralove, Charles University, Hradec Kralove, Czech Republic. 2. Department of Psychological Sciences, University of Bristol, Bristol, BS8 1TH, UK. 3. Department of Community Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 4. Department of Pharmaceutical Sciences, University College of Pharmaceutical Sciences, Hanamkonda, 506009, Telangana, India. 5. Health Research Institute, University of Canberra, Canberra, Australia. wubshet.tesfaye@sydney.edu.au. 6. Sydney Pharmacy School, The University of Sydney, Sydney, NSW, Australia. wubshet.tesfaye@sydney.edu.au.
Abstract
PURPOSE: Recent studies have suggested a lower risk of hepatocellular carcinoma (HCC) in patients receiving selective serotonin reuptake inhibitors (SSRIs). The current study aimed to provide an updated and comprehensive assessment of the association between SSRI use and development of HCC. METHODS: This is a systematic review and meta-analysis of all observational studies published until June 2021. We comprehensively searched PubMed/Medline, Web of Science, and Embase to identify studies comparing SSRIs use with control in relation to the risk of HCC. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between SSRI use and incident HCC risk using random-effects meta-analysis. A dose-response analysis was conducted to evaluate the HCC risk according to the defined daily dose (DDD) of SSRI use. RESULTS: Eight observational studies, comprising 1,051,096 participants and 22,316 incidences of HCC, examining the association between SSRIs use and HCC risk, were included in the systematic review (adjusted RR: 0.66; 95% CI: 0.56-0.79; P ≤ 0.001). In subgroup analysis, the magnitude of benefit associated with SSRIs was significantly higher in patients with hepatitis infection (RR: 0.70, 95% CI: 0.51-0.95) than the general population (Pheterogeneity = 0.700). The dose-response analysis indicated strong inverse association between cumulative DDD of SSRI and risk of HCC (coefficient: - 0.0030; P = 0.002; R2 = 0.78). CONCLUSIONS: The results of this review show that SSRI use was associated with a 34% lower risk of HCC, which tend to be dose dependent. Further prospective studies are warranted to confirm these observations across the spectrum of chronic liver disease and hepatitis infection.
PURPOSE: Recent studies have suggested a lower risk of hepatocellular carcinoma (HCC) in patients receiving selective serotonin reuptake inhibitors (SSRIs). The current study aimed to provide an updated and comprehensive assessment of the association between SSRI use and development of HCC. METHODS: This is a systematic review and meta-analysis of all observational studies published until June 2021. We comprehensively searched PubMed/Medline, Web of Science, and Embase to identify studies comparing SSRIs use with control in relation to the risk of HCC. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between SSRI use and incident HCC risk using random-effects meta-analysis. A dose-response analysis was conducted to evaluate the HCC risk according to the defined daily dose (DDD) of SSRI use. RESULTS: Eight observational studies, comprising 1,051,096 participants and 22,316 incidences of HCC, examining the association between SSRIs use and HCC risk, were included in the systematic review (adjusted RR: 0.66; 95% CI: 0.56-0.79; P ≤ 0.001). In subgroup analysis, the magnitude of benefit associated with SSRIs was significantly higher in patients with hepatitis infection (RR: 0.70, 95% CI: 0.51-0.95) than the general population (Pheterogeneity = 0.700). The dose-response analysis indicated strong inverse association between cumulative DDD of SSRI and risk of HCC (coefficient: - 0.0030; P = 0.002; R2 = 0.78). CONCLUSIONS: The results of this review show that SSRI use was associated with a 34% lower risk of HCC, which tend to be dose dependent. Further prospective studies are warranted to confirm these observations across the spectrum of chronic liver disease and hepatitis infection.