David E Kaplan1, Marina A Serper2, Rajni Mehta3, Rena Fox4, Binu John5, Ayse Aytaman6, Michelle Baytarian7, Kristel Hunt8, Jeffrey Albrecht9, Basile Njei3, Tamar H Taddei3. 1. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: dakaplan@pennmedicine.upenn.edu. 2. Corporal Michael J. Crescenz VA Medical Center, Philadelphia, Pennsylvania; Division of Gastroenterology and Hepatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 3. VA Connecticut Healthcare System, West Haven, Connecticut. 4. San Francisco VA Medical Center, San Francisco, California. 5. Hunter Holmes McGuire VA Medical Center, Richmond, Virginia. 6. VA New York Harbor Health Care System, Brooklyn, New York. 7. Boston VA Healthcare System, Boston, Massachusetts. 8. James J. Peters VA Medical Center, Bronx, New York. 9. Minneapolis VA Medical Center, Minneapolis, Minnesota.
Abstract
BACKGROUND & AIMS: Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. RESULTS: In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. CONCLUSIONS: In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.
BACKGROUND & AIMS: Concerns related to hepatotoxicity frequently lead to discontinuation or non-initiation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase therapy in patients with cirrhosis despite data supporting statin use. We investigated the independent effects of hyperlipidemia and statin exposure on mortality, hepatic decompensation, and hepatocellular carcinoma development in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients with newly diagnosed cirrhosis from January 1, 2008 through June 30, 2016 in the Veterans Health Administration. Subjects were divided into 2 cohorts: 21,921 patients with prior statin exposure (existing users) and 51,023 statin-naïve individuals, of whom 8794 subsequently initiated statin therapy (new initiators) and 44,269 did not (non-initiators). Multivariable Cox proportional hazard models with inverse probability weighting were constructed to assess the effects of time-updating lipid profiles and cumulative exposure to statins on survival and hepatic decompensation. Statin-naïve new initiators were propensity matched with non-initiators to simulate a randomized controlled trial of statin use in cirrhosis. RESULTS: In statin-naïve subjects, every 10-mg/dL increase in baseline total cholesterol was associated with a 3.6% decrease in mortality. In existing users, each year of continued statin exposure was associated with a hazard ratio of 0.920 (95% confidence interval 0.0.897-0.943) for mortality. After risk-set matching, each year of statin exposure among new initiators was associated with a hazard ratio of 0.913 (95% confidence interval 0.890-0.937) for mortality. CONCLUSIONS: In a retrospective cohort study of veterans with a new diagnosis of cirrhosis, we associated hypercholesterolemia with well-preserved hepatic function and decreased mortality. Nonetheless, each cumulative year of statin exposure was associated with an independent 8.0%-8.7% decrease of mortality of patients with cirrhosis of Child-Turcotte-Pugh classes A and B.
Authors: Tracey G Simon; Ann-Sofi Duberg; Soo Aleman; Hannes Hagstrom; Long H Nguyen; Hamed Khalili; Raymond T Chung; Jonas F Ludvigsson Journal: Ann Intern Med Date: 2019-08-20 Impact factor: 25.391
Authors: Marina Serper; David E Kaplan; Justine Shults; Peter P Reese; Lauren A Beste; Tamar H Taddei; Rachel M Werner Journal: Hepatology Date: 2019-06-26 Impact factor: 17.425
Authors: Wenshu Tang; Jingying Zhou; Weiqin Yang; Yu Feng; Haoran Wu; Myth T S Mok; Lingyun Zhang; Zhixian Liang; Xiaoyu Liu; Zhewen Xiong; Xuezhen Zeng; Jing Wang; Jiahuan Lu; Jingqing Li; Hanyong Sun; Xiaoyu Tian; Philip Chun Yeung; Yong Hou; Heung Man Lee; Candice C H Lam; Howard H W Leung; Anthony W H Chan; Ka Fai To; John Wong; Paul B S Lai; Kelvin K C Ng; Simon K H Wong; Vincent W S Wong; Alice P S Kong; Joseph J Y Sung; Alfred S L Cheng Journal: Cell Mol Immunol Date: 2022-05-20 Impact factor: 22.096
Authors: Marina Serper; Ethan M Weinberg; Jordana B Cohen; Peter P Reese; Tamar H Taddei; David E Kaplan Journal: Hepatology Date: 2020-11-09 Impact factor: 17.425
Authors: Binu V John; Kaley Schwartz; Cynthia Levy; Bassam Dahman; Yangyang Deng; Paul Martin; Tamar H Taddei; David E Kaplan Journal: Hepatol Commun Date: 2021-05-06