title: Nonsteroidal anti-inflammatory drug use, chronic liver disease, and hepatocellular carcinoma.
abstract: BACKGROUND
  Nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce chronic inflammation and risk of many cancers, but their effect on risk of hepatocellular carcinoma (HCC) and death due to chronic liver disease (CLD) has not been investigated.
  
  
  METHODS
  We analyzed prospective data on 300504 men and women aged 50 to 71 years in the National Institutes of Health-AARP Diet and Health Study cohort and linked self-reported aspirin and nonaspirin NSAID use with registry-confirmed diagnoses of HCC (n=250) and death due to CLD (n=428, excluding HCC). We calculated hazard rate ratios (RRs) and their two-sided 95% confidence intervals (CIs) using Cox proportional hazard regression models with adjustment for age, sex, race/ethnicity, cigarette smoking, alcohol consumption, diabetes, and body mass index. All tests of statistical significance were two-sided.
  
  
  RESULTS
  Aspirin users had statistically significant reduced risks of incidence of HCC (RR = 0.59; 95% CI = 0.45 to 0.77) and mortality due to CLD (RR = 0.55; 95% CI = 0.45 to 0.67) compared to those who did not use aspirin. In contrast, users of nonaspirin NSAIDs had a reduced risk of mortality due to CLD (RR = 0.74; 95% CI= 0.61 to 0.90) but did not have lower risk of incidence of HCC (RR = 1.08; 95% CI = 0.84 to 1.39) compared to those who did not use nonaspirin NSAIDs. The risk estimates did not vary in statistical significance by frequency (monthly, weekly, daily) of aspirin use, but the reduced risk of mortality due to CLD was statistically significant only among monthly users of nonaspirin NSAIDs compared to non-users.
  
  
  CONCLUSIONS
  Aspirin use was associated with reduced risk of developing HCC and of death due to CLD whereas nonaspirin NSAID use was only associated with reduced risk of death due to CLD.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Blvd, EPS 5032, Rockville, MD 20852, USA. vikrant.sahasrabuddhe@nih.gov
authors.forename: Vikrant V
authors.initials: VV
authors.lastname: Sahasrabuddhe
authors.forename: Munira Z
authors.initials: MZ
authors.lastname: Gunja
authors.forename: Barry I
authors.initials: BI
authors.lastname: Graubard
authors.forename: Britton
authors.initials: B
authors.lastname: Trabert
authors.forename: Lauren M
authors.initials: LM
authors.lastname: Schwartz
authors.forename: Yikyung
authors.initials: Y
authors.lastname: Park
authors.forename: Albert R
authors.initials: AR
authors.lastname: Hollenbeck
authors.forename: Neal D
authors.initials: ND
authors.lastname: Freedman
authors.forename: Katherine A
authors.initials: KA
authors.lastname: McGlynn
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D001241:Aspirin / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology* / Q000401:mortality; D002908:Chronic Disease; D015897:Comorbidity; D051545:Cyclooxygenase 1 / Q000187:drug effects; D051546:Cyclooxygenase 2; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage; D005260:Female; D006801:Humans; D015994:Incidence; D008107:Liver Diseases / Q000453:epidemiology* / Q000401:mortality; D008113:Liver Neoplasms / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D001241:Aspirin