Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 1;6(6):e2320222.
doi: 10.1001/jamanetworkopen.2023.20222.

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

Mara Sophie Vell  1 , Rohit Loomba  2 , Arunkumar Krishnan  3 , Kirk J Wangensteen  4   5 , Jonel Trebicka  6 , Kate Townsend Creasy  7 , Christian Trautwein  1 , Eleonora Scorletti  4 , Katharina Sophie Seeling  1 , Leonida Hehl  1 , Miriam Daphne Rendel  1 , Inuk Zandvakili  4 , Tang Li  8 , Jinbo Chen  8 , Marijana Vujkovic  4 , Saleh Alqahtani  9   10 , Daniel James Rader  4   11 , Kai Markus Schneider  1 , Carolin Victoria Schneider  1   4   11
Affiliations

Association of Statin Use With Risk of Liver Disease, Hepatocellular Carcinoma, and Liver-Related Mortality

Mara Sophie Vell et al. JAMA Netw Open. .

Abstract

Importance: Given the burden of chronic liver disease on the health care system, more information on the hepatoprotective association of statins in the general population is needed.

Objective: To examine whether regular statin use is associated with a reduction in liver disease, particularly hepatocellular carcinoma (HCC) and liver-related deaths, in the general population.

Design, setting, and participants: This cohort study used data from the UK Biobank (UKB) (individuals aged 37-73 years) collected from baseline (2006-2010) to the end of follow-up in May 2021, from the TriNetX cohort (individuals aged 18-90 years) enrolled from baseline (2011-2020) until end of follow-up in September 2022, and from the Penn Medicine Biobank (PMBB) (individuals aged 18-102 years) with ongoing enrollment starting in 2013 to the end of follow-up in December 2020. Individuals were matched using propensity score matching according to the following criteria: age, sex, body mass index, ethnicity, diabetes with or without insulin or biguanide use, hypertension, ischemic heart disease, dyslipidemia, aspirin use, and number of medications taken (UKB only). Data analysis was performed from April 2021 to April 2023.

Exposure: Regular statin use.

Main outcomes and measures: Primary outcomes were liver disease and HCC development as well as liver-associated death.

Results: A total of 1 785 491 individuals were evaluated after matching (aged 55 to 61 years on average, up to 56% men, and up to 49% women). A total of 581 cases of liver-associated death, 472 cases of incident HCC, and 98 497 new liver diseases were registered during the follow-up period. Individuals were aged 55-61 years on average, with a slightly higher proportion of men (up to 56%). In UKB individuals (n = 205 057) without previously diagnosed liver disease, statin users (n = 56 109) had a 15% lower hazard ratio (HR) for the association of developing a new liver disease (HR, 0.85; 95% CI, 0.78-0.92; P < .001). In addition, statin users demonstrated a 28% lower HR for the association with liver-related death (HR, 0.72; 95% CI, 0.59-0.88; P = .001) and a 42% lower HR for the development of HCC (HR, 0.58; 95% CI, 0.35-0.96; P = .04). In TriNetX individuals (n = 1 568 794), the HR for the association of HCC was reduced even further for statin users (HR, 0.26; 95% CI, 0.22-0.31; P = .003). The hepatoprotective association of statins was time and dose dependent, with a significant association in PMBB individuals (n = 11 640) for incident liver diseases after 1 year of statin use (HR, 0.76; 95% CI, 0.59-0.98; P = .03). Taking statins was particularly beneficial in men, individuals with diabetes, and individuals with a high Fibrosis-4 index at baseline. Carriers of the heterozygous minor allele of PNPLA3 rs738409 benefited from statin use and had a 69% lower HR for the association with HCC (UKB HR, 0.31; 95% CI, 0.11-0.85; P = .02).

Conclusions and relevance: This cohort study indicates substantial preventive associations of statins against liver disease, with an association with duration and dose of intake.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Loomba reported serving as a consultant for and/or receiving grants from Aardvark Therapeutics, Altimmune, Anylam/Regeneron, Amgen, Arrowhead Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb, CohBar, Eli Lilly, Galmed, Gilead, Glympse, Hightide, Inipharma, Intercept, Inventiva, Ionis, Janssen Inc, Madrigal, Metacrine Inc, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Merck, Pfizer, Sagimet, Theratechnologies, 89 bio, Terns Pharmaceuticals, Viking Therapeutics, Boehringer-Ingelheim, Galectin Therapeutics, Hanmi, and Sonic Incytes outside the submitted work and being a cofounder of LipoNexus Inc. No other disclosures were reported.

Figures

Figure.
Figure.. Flowchart of the UK Biobank, Penn Medicine Biobank (PMBB), and TriNetX Cohorts
C22.0 indicates hepatocellular carcinoma.
See this image and copyright information in PMC

References

    1. Mokdad AA, Lopez AD, Shahraz S, et al. . Liver cirrhosis mortality in 187 countries between 1980 and 2010: a systematic analysis. BMC Med. 2014;12(1):145. doi:10.1186/s12916-014-0145-y - DOI - PMC - PubMed
    1. Lozano R, Naghavi M, Foreman K, et al. . Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2095-2128. doi:10.1016/S0140-6736(12)61728-0 - DOI - PMC - PubMed
    1. Feldt M, Bjarnadottir O, Kimbung S, et al. . Statin-induced anti-proliferative effects via cyclin D1 and p27 in a window-of-opportunity breast cancer trial. J Transl Med. 2015;13(1):133. doi:10.1186/s12967-015-0486-0 - DOI - PMC - PubMed
    1. Sorrentino G, Ruggeri N, Specchia V, et al. . Metabolic control of YAP and TAZ by the mevalonate pathway. Nat Cell Biol. 2014;16(4):357-366. doi:10.1038/ncb2936 - DOI - PubMed
    1. Hao F, Xu Q, Wang J, et al. . Lipophilic statins inhibit YAP nuclear localization, co-activator activity and colony formation in pancreatic cancer cells and prevent the initial stages of pancreatic ductal adenocarcinoma in KrasG12D mice. PLoS One. 2019;14(5):e0216603. doi:10.1371/journal.pone.0216603 - DOI - PMC - PubMed

Publication types

MeSH terms

Substances