Are selective serotonin reuptake inhibitors associated with hepatocellular carcinoma in patients with hepatitis C?
OBJECTIVE
Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients with chronic hepatitis C virus (HCV) infection. Research suggests that serotonin promotes the development and growth of hepatocellular carcinoma (HCC). We tested the hypothesis whether exposure to SSRIs is associated with an increased risk of HCC in HCV patients.


METHODS
Patients who entered the United States Veterans Affairs (VA) Hepatitis C Clinical Case Registry in 2000 to 2009 were analyzed. During the 8 years of follow-up, 36,192 patients filled at least 1 SSRI prescription. Cases of HCC were identified by diagnosis codes (ICD-9 155.0). Multivariable Cox regression analyses estimated adjusted HCC hazard ratios (HRs) for SSRI-exposed versus SSRI-unexposed subjects and categories of average SSRI doses.


RESULTS
The annual incidence of HCC in the VA registry cohort of 109,736 patients was 0.5% and significantly greater in the 8% with cirrhosis at baseline (HR = 5.2; 95% CI, 4.7-5.7). There was no evidence for significant interactions between the effect of SSRI-exposure and cirrhosis. Baseline characteristics of the exposed (n = 36,192) and unexposed (n = 73,544) subjects were similar. The median (interquartile range [IQR]) follow-up period after SSRI-exposure began was 44 (20-74) months with 18 (3-49) months between the first and last prescription. The median average SSRI dose during follow-up expressed as a fraction of initial recommended doses for depression was 0.94 (IQR, 0.5 to 1.3). The risk of HCC was not significantly increased after SSRI exposure (HR = 0.96; 95% CI, 0.87-1.05) or with increasing SSRI doses.


CONCLUSIONS
Analysis of a large cohort of HCV patients did not support the hypothesis that SSRIs increase the risk of developing HCC.
Departments of Medicine and Psychiatry, Veterans Health System Minneapolis and the University of Minnesota Medical School.
Christine
C
Pocha
Astrid
A
Knott
Thomas S
TS
Rector
Eric
E
Dieperink
D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000453:epidemiology; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012042:Registries / Q000706:statistics & numerical data*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs / Q000706:statistics & numerical data
D017367:Selective Serotonin Reuptake Inhibitors