Tracey G. Simon, MD, MPH; Ann-Sofi Duberg, MD, PhD; Soo Aleman, MD, PhD; Hannes Hagstrom, MD, PhD; Long H. Nguyen, MD, MPH; Hamed Khalili, MD, MPH; Raymond T. Chung, MD; Jonas F. Ludvigsson, MD, PhD
Note: Dr. Ludvigsson had access to all data in the study and was responsible for the decision to submit the manuscript for publication.
Grant Support: Dr. Simon was supported by a North American Training Grant from the American College of Gastroenterology. Dr. Duberg was supported by a research ALF grant from Region Örebro County (OLL-683801). Dr. Hagstrom was supported by a Stockholm County Council clinical postdoctoral appointment. Dr. Khalili was supported by grant K23 DK099681 from the National Institutes of Health. Dr. Chung was supported by grant K24 DK078772 from the National Institutes of Health.
Disclosures: Dr. Duberg reports personal fees from AbbVie, Bristol-Myers Squibb, Gilead, Janssen, and MSD outside the submitted work. Dr. Aleman reports honoraria for lectures and expert group discussions from AbbVie, Bristol-Myers Squibb, Gilead, and MSD and grants from AbbVie and Gilead outside the submitted work. Dr. Chung reports grants from Gilead Sciences, MassBiologics, Merck, AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Synlogic, Roche, and Kaleido and personal fees from Alnylam outside the submitted work. Dr. Ludvigsson reports other support from Janssen outside the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-2753.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement: Study protocol: Available from Dr. Ludvigsson (e-mail, firstname.lastname@example.org). Statistical code and data set: Not available.
Corresponding Author: Jonas F. Ludvigsson, MD, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-17177 Stockholm, Sweden; e-mail, email@example.com.
Current Author Addresses: Drs. Simon and Chung: Massachusetts General Hospital, Liver Center, Division of Gastroenterology, 55 Fruit Street, Blake 4, Boston, MA 02114.
Dr. Duberg: Örebro University Hospital, Department of Infectious Diseases, School of Medical Sciences, Faculty of Medicine and Health, SE-701 85 Örebro, Sweden.
Dr. Aleman: Karolinska University Hospital, Huddinge, Division of Infection and Dermatology, 141 86 Stockholm, Sweden.
Dr. Hagstrom: Karolinska University Hospital, Huddinge, Center for Digestive Diseases, Hepatology Unit, 141 86 Stockholm, Sweden.
Dr. Nguyen: Massachusetts General Hospital, Division of Gastroenterology, 55 Fruit Street, Blake 4, Boston, MA 02114.
Dr. Khalili: Massachusetts General Hospital Crohns and Colitis Center, 165 Cambridge Street, 9th Floor, Boston, MA 02114.
Dr. Ludvigsson: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, PO Box 281, SE-17177 Stockholm, Sweden.
Author Contributions: Conception and design: T.G. Simon, R.T. Chung, J.F. Ludvigsson.
Analysis and interpretation of the data: T.G. Simon, A.S. Duberg, S. Aleman, H. Hagstrom, H. Khalili, R.T. Chung, J.F. Ludvigsson.
Drafting of the article: T.G. Simon, S. Aleman, H. Khalili, J.F. Ludvigsson.
Critical revision of the article for important intellectual content: T.G. Simon, A.S. Duberg, S. Aleman, H. Hagstrom, L.H. Nguyen, R.T. Chung, J.F. Ludvigsson.
Final approval of the article: T.G. Simon, A.S. Duberg, S. Aleman, H. Hagstrom, L.H. Nguyen, H. Khalili, R.T. Chung, J.F. Ludvigsson.
Provision of study materials or patients: A.S. Duberg, J.F. Ludvigsson.
Statistical expertise: T.G. Simon, L.H. Nguyen.
Obtaining of funding: J.F. Ludvigsson.
Administrative, technical, or logistic support: L.H. Nguyen, J.F. Ludvigsson.
Collection and assembly of data: T.G. Simon, A.S. Duberg, L.H. Nguyen, J.F. Ludvigsson.
Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown.
To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis.
Prospective propensity score (PS)–matched cohort.
Swedish registers, 2005 to 2013.
A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults.
Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs).
Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], −4.8 percentage points [95% CI, −6.2 to −3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, −1.2 percentage points [CI, −2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, −5.9 percentage points [CI, −7.6 to −4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, −7.9 percentage points [CI, −9.6 to −6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, −4.5 percentage points [CI, −6.0 to −3.0 percentage points]) statin users.
Lack of lipid, fibrosis, or HCC surveillance data.
In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC.
Simon TG, Duberg A, Aleman S, et al. Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population. Ann Intern Med. 2019;171:318–327. [Epub ahead of print 20 August 2019]. doi: https://doi.org/10.7326/M18-2753
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Published: Ann Intern Med. 2019;171(5):318-327.
Published at www.annals.org on 20 August 2019
Cardiology, Coronary Risk Factors, Dyslipidemia.
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