Effects of Statins on the Hepatic Decompensation, Mortality, Complications and Drug Safety in Liver Cirrhosis: A Systematic Review and Meta-Analysis
American Journal of Internal Medicine
Volume 6, Issue 5, September 2018, Pages: 108-120
Received: Jul. 13, 2018; Accepted: Jul. 26, 2018; Published: Aug. 31, 2018
Views 1198      Downloads 110
Xinxing Tantai, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Longbao Yang, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Zhongcao Wei, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Cailan Xiao, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Lirong Chen, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Jinhai Wang, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Na Liu, Division of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China
Article Tools
Follow on us
Background and Aim: Evidence indicates statins seem to improve outcomes in cirrhotic patients. Systematic review and meta-analysis are performed to evaluate the effect and safety of statins in the setting of cirrhosis. Methods: We searched PubMed, EMBASE, and the Cochrane Library from inception through January 2018 to identify comparative studies evaluating the role of statins in cirrhosis. Pooled risk estimates with 95% confidence intervals were calculated using a random effects model. Results: Eight studies (4 retrospective cohort studies and 4 randomized controlled trials) involving 3,966 cirrhotic patients were included. Statin use was associated with 56% lower risk of progression to decompensated cirrhosis (RR, 0.44; 95% CI, 0.36–0.54) and 47% lower risk of mortality (RR, 0.53; 95% CI, 0.47–0.61). Subgroup analyses showed that these results were generally consistent regardless of study design, etiology of cirrhosis, stage of cirrhosis, follow-up time, method of identifying cirrhosis. For initial variceal bleeding, pooled RR was 0.48 (0.35–0.67). For ascites, pooled RR was 0.66 (0.45–0.99). For portal hypertension, using statins could increase the HVPG response rate, pooled RR was 2.61(1.03–6.62). For hepatocellular carcinoma, pooled RR was 0.47(0.36–0.63). For any adverse event and serious adverse events, using statins was almost equivalent to nonusers, pooled RR was 1.06 (0.50-2.25) and 0.77 (0.31–1.95). Conclusions: Statin use may be associated with reduced risk of hepatic decompensation and mortality in cirrhosis with well tolerated. Additionally, statin use appears to decrease portal hypertension and reduce the risk of initial variceal bleeding, ascites and hepatocellular carcinoma. Further RCTs will be required to confirm our findings.
Statin, Liver Cirrhosis, Decompensation, Mortality, Meta-analysis
To cite this article
Xinxing Tantai, Longbao Yang, Zhongcao Wei, Cailan Xiao, Lirong Chen, Jinhai Wang, Na Liu, Effects of Statins on the Hepatic Decompensation, Mortality, Complications and Drug Safety in Liver Cirrhosis: A Systematic Review and Meta-Analysis, American Journal of Internal Medicine. Vol. 6, No. 5, 2018, pp. 108-120. doi: 10.11648/j.ajim.20180605.14
Copyright © 2018 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A et al. The Epidemiology of Cirrhosis in the United States: A Population-based Study. J Clin Gastroenterol 2015; 49:690-6.
D'Amico G, Pasta L, Morabito A, D'Amico M, Caltagirone M, Malizia G et al. Competing risks and prognostic stages of cirrhosis: a 25-year inception cohort study of 494 patients. Aliment Pharmacol Ther 2014; 39:1180-93.
D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol 2006; 44:217-31.
Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet 2014; 383:1749-61.
Tripathi D, Stanley AJ, Hayes PC, Patch D, Millson C, Mehrzad H et al. U.K. guidelines on the management of variceal haemorrhage in cirrhotic patients. Gut 2015; 64:1680-704.
Douglas I, Evans S, Smeeth L. Effect of statin treatment on short term mortality after pneumonia episode: cohort study. BMJ 2011; 342:d1642.
Palmer SC, Craig JC, Navaneethan SD, Tonelli M, Pellegrini F, Strippoli GF. Benefits and harms of statin therapy for persons with chronic kidney disease: a systematic review and meta-analysis. Ann Intern Med 2012; 157:263-75.
Marcella SW, David A, Ohman-Strickland PA, Carson J, Rhoads GG. Statin use and fatal prostate cancer: a matched case-control study. Cancer-Am Cancer Soc 2012; 118:4046-52.
Tsan YT, Lee CH, Wang JD, Chen PC. Statins and the risk of hepatocellular carcinoma in patients with hepatitis B virus infection. J Clin Oncol 2012; 30:623-30.
Voorneveld PW, Reimers MS, Bastiaannet E, Jacobs RJ, van Eijk R, Zanders M et al. Statin Use After Diagnosis of Colon Cancer and Patient Survival. Gastroenterology 2017; 153:470-9.
Marrone G, Maeso-Diaz R, Garcia-Cardena G, Abraldes JG, Garcia-Pagan JC, Bosch J et al. KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: behind the molecular mechanisms of statins. Gut 2015; 64:1434-43.
Abraldes JG, Rodriguez-Vilarrupla A, Graupera M, Zafra C, Garcia-Caldero H, Garcia-Pagan JC et al. Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4 cirrhotic rats. J Hepatol 2007; 46:1040-6.
Bang UC, Benfield T, Bendtsen F. Reduced risk of decompensation and death associated with use of statins in patients with alcoholic cirrhosis. A nationwide case-cohort study. Aliment Pharmacol Ther 2017; 46:673-80.
Chang FM, Wang YP, Lang HC, Tsai CF, Hou MC, Lee FY et al. Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study. Hepatology 2017; 66:896-907.
Parra JL, Reddy KR. Hepatotoxicity of hypolipidemic drugs. Clin Liver Dis 2003; 7:415-33.
Argo CK, Loria P, Caldwell SH, Lonardo A. Statins in liver disease: a molehill, an iceberg, or neither? Hepatology 2008; 48:662-9.
Chalasani N, Aljadhey H, Kesterson J, Murray MD, Hall SD. Patients with elevated liver enzymes are not at higher risk for statin hepatotoxicity. Gastroenterology 2004; 126:1287-92.
Pollo-Flores P, Soldan M, Santos UC, Kunz DG, Mattos DE, Da Silva AC et al. Three months of simvastatin therapy vs. placebo for severe portal hypertension in cirrhosis: A randomized controlled trial. Digest Liver Dis 2015; 47:957-63.
Lewis JH, Mortensen ME, Zweig S, Fusco MJ, Medoff JR, Belder R. Efficacy and safety of high-dose pravastatin in hypercholesterolemic patients with well-compensated chronic liver disease: Results of a prospective, randomized, double-blind, placebo-controlled, multicenter trial. Hepatology 2007; 46:1453-63.
Garcia-Tsao G, Abraldes JG, Berzigotti A, Bosch J. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology 2017; 65:310-35.
de Franchis R. Expanding consensus in portal hypertension: Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension. J Hepatol 2015; 63:743-52.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 2009; 151:W65-94.
Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000; 283:2008-12.
Scherer RW, Langenberg P, von Elm E. Full publication of results initially presented in abstracts. Cochrane Database Syst Rev 2007:R5.
Mohanty A, Tate JP, Garcia-Tsao G. Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C-Related Compensated Cirrhosis. Gastroenterology 2016; 150:430-40.
Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci 2014; 59:1958-65.
Abraldes JG, Albillos A, Banares R, Turnes J, Gonzalez R, Garcia-Pagan JC et al. Simvastatin lowers portal pressure in patients with cirrhosis and portal hypertension: a randomized controlled trial. Gastroenterology 2009; 136:1651-8.
Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J et al. Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients With Cirrhosis. Gastroenterology 2016; 150:1160-1170.
Bishnu S, Ahammed SM, Sarkar A, Hembram J, Chatterjee S, Das K et al. Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension: a proof-of-concept study. Eur J Gastroenterol Hepatol 2018; 30:54-9.
Kamal S, Khan MA, Seth A, Cholankeril G, Gupta D, Singh U et al. Beneficial Effects of Statins on the Rates of Hepatic Fibrosis, Hepatic Decompensation, and Mortality in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Am J Gastroenterol 2017; 112:1495-505.
Ma X, Sun D, Li C, Ying J, Yan Y. Statin use and virus-related cirrhosis: A systemic review and meta-analysis. Clin Res Hepatol Gastroenterol 2017; 41:533-42.
Kim RG, Loomba R, Prokop LJ, Singh S. Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2017; 15:1521-30.
Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology 2004; 127:S35-50.
Trebicka J, Hennenberg M, Laleman W, Shelest N, Biecker E, Schepke M et al. Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology 2007; 46:242-53.
Tsochatzis EA, Bosch J. Statins in cirrhosis-Ready for prime time. Hepatology 2017; 66:697-9.
Chalasani N. Statins and hepatotoxicity: focus on patients with fatty liver. Hepatology 2005; 41:690-5.
Vuppalanchi R, Teal E, Chalasani N. Patients with elevated baseline liver enzymes do not have higher frequency of hepatotoxicity from lovastatin than those with normal baseline liver enzymes. Am J Med Sci 2005; 329:62-5.
Khorashadi S, Hasson NK, Cheung RC. Incidence of statin hepatotoxicity in patients with hepatitis C. Clin Gastroenterol Hepatol 2006; 4:902-7, 806.
Wright AP, Adusumalli S, Corey KE. Statin therapy in patients with cirrhosis. Frontline Gastroenterol 2015; 6:255-61.
Joy TR, Hegele RA. Narrative review: statin-related myopathy. Ann Intern Med 2009; 150:858-68.
Science Publishing Group
1 Rockefeller Plaza,
10th and 11th Floors,
New York, NY 10020
Tel: (001)347-983-5186