Nadim Mahmud1, Sara Chapin2, David S Goldberg3, K Rajender Reddy4, Tamar H Taddei5, David E Kaplan6. 1. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA; Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Leonard David Institute of Health Economics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. Electronic address: nadim@pennmedicine.upenn.edu. 2. Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA. 4. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 5. Division of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA; VA Connecticut Healthcare System, West Haven, CT, USA. 6. Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Abstract
BACKGROUNDS & AIMS: There is a need to identify therapies that prevent the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into 3 groups based on statin exposure (statin naïve, existing statin user, and new statin initiator). Cox proportional hazards regression models with inverse probability treatment weighting and marginal structural models were utilized to comprehensively address potential confounding in estimating the association between time-updated statin exposure and first occurrence of high-grade ACLF. RESULTS: The cohort included 84,963 patients, of whom 26.9% were on a statin at baseline. A total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF over a median follow-up time of 51.6 months (IQR 27.5-81.4). Time-updated statin use was associated with a significant reduction in the hazard of developing ACLF (hazard ratio [HR] 0.62, 95% CI 0.59-0.65, p <0.001). Increasing doses of statin were associated with progressively reduced hazard of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p <0.001 for <20 mg vs. 0 mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p <0.001 for >20 mg vs. 0 mg statin exposure). Furthermore, every additional 5 months of statin exposure was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92, p <0.001). CONCLUSIONS: In this large, retrospective, cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF. LAY SUMMARY: Statin therapy has been shown to have numerous beneficial effects in patients with chronic liver disease. This study demonstrated a strong association between statin therapy and a reduced risk of acute-on-chronic liver failure development in patients with cirrhosis. The results of this study support the promising role that statins may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.
BACKGROUNDS & AIMS: There is a need to identify therapies that prevent the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis. METHODS: We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into 3 groups based on statin exposure (statin naïve, existing statin user, and new statin initiator). Cox proportional hazards regression models with inverse probability treatment weighting and marginal structural models were utilized to comprehensively address potential confounding in estimating the association between time-updated statin exposure and first occurrence of high-grade ACLF. RESULTS: The cohort included 84,963 patients, of whom 26.9% were on a statin at baseline. A total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF over a median follow-up time of 51.6 months (IQR 27.5-81.4). Time-updated statin use was associated with a significant reduction in the hazard of developing ACLF (hazard ratio [HR] 0.62, 95% CI 0.59-0.65, p <0.001). Increasing doses of statin were associated with progressively reduced hazard of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p <0.001 for <20 mg vs. 0 mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p <0.001 for >20 mg vs. 0 mg statin exposure). Furthermore, every additional 5 months of statin exposure was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92, p <0.001). CONCLUSIONS: In this large, retrospective, cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF. LAY SUMMARY: Statin therapy has been shown to have numerous beneficial effects in patients with chronic liver disease. This study demonstrated a strong association between statin therapy and a reduced risk of acute-on-chronic liver failure development in patients with cirrhosis. The results of this study support the promising role that statins may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.
Authors: Javier Fernández; Juan Acevedo; Reiner Wiest; Thierry Gustot; Alex Amoros; Carme Deulofeu; Enric Reverter; Javier Martínez; Faouzi Saliba; Rajiv Jalan; Tania Welzel; Marco Pavesi; María Hernández-Tejero; Pere Ginès; Vicente Arroyo Journal: Gut Date: 2017-08-28 Impact factor: 23.059
Authors: Elisa Pose; Laura Napoleone; Ahmed Amin; Daniela Campion; César Jimenez; Salvatore Piano; Olivier Roux; Frank Erhard Uschner; Koos de Wit; Giacomo Zaccherini; Carlo Alessandria; Paolo Angeli; Mauro Bernardi; Ulrich Beuers; Paolo Caraceni; François Durand; Rajeshwar P Mookerjee; Jonel Trebicka; Victor Vargas; Raúl J Andrade; Marta Carol; Judit Pich; Juan Ferrero; Gema Domenech; Marta Llopis; Ferran Torres; Patrick S Kamath; Juan G Abraldes; Elsa Solà; Pere Ginès Journal: Lancet Gastroenterol Hepatol Date: 2019-10-10