title: Statins and Reduced Risk of Liver Cancer: Evidence for Confounding.
abstract: A negative association of statin use with liver cancer risk has been reported frequently. We added laboratory measurements, to our knowledge not included in previous investigations, to a case-control analysis of 2877 case patients and 142 850 matched control subjects enrolled in Kaiser Permanente Northern California. Addressing confounding by indication by restricting subjects to those with elevated cholesterol greatly attenuated the negative association; eg, the multivariable-adjusted odds ratio (OR) rose from 0.41 (95% confidence interval [CI] = 0.35 to 0.49) to 0.87 (95% CI = 0.55 to 1.39) for receipt of 18 or more prescriptions. Confounding by contraindication was addressed by controlling for degree of abnormality of liver function tests, alanine or aspartate transaminase, measured within one year of the elevated cholesterol and strongly related to risk. The negative association of statins disappeared for all numbers of prescriptions received, with an odds ratio of 1.21 (95% CI = 0.53 to 2.75) for 18 or more prescriptions. Findings cast doubt on the causality of the frequently observed preventive association.
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA (GDF, NA, BF, LAH); Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (GDF, LAH). gdf@dor.kaiser.org.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Friedman
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA (GDF, NA, BF, LAH); Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (GDF, LAH).
authors.forename: Ninah
authors.initials: N
authors.lastname: Achacoso
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA (GDF, NA, BF, LAH); Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (GDF, LAH).
authors.forename: Bruce
authors.initials: B
authors.lastname: Fireman
authors.affiliation: Division of Research, Kaiser Permanente Medical Care Program, Oakland, CA (GDF, NA, BF, LAH); Department of Health Research and Policy, Stanford University School of Medicine, Stanford, CA (GDF, LAH).
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy; D008113:Liver Neoplasms / Q000453:epidemiology*; D016017:Odds Ratio; D065840:Protective Factors
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase