Skip to main content
Top
Published in: BMC Gastroenterology 1/2019

Open Access 01-12-2019 | Hepatic Encephalopathy | Research article

Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: a systematic review and meta-analysis

Authors: Yue Gu, Xueqin Yang, Hang Liang, Deli Li

Published in: BMC Gastroenterology | Issue 1/2019

Login to get access

Abstract

Background

Statin has been more and more widely used in chronic liver disease, however, existed studies have attained contradictory results. According to the present study, we aimed to test the efficacy and safety of statin via a meta-analysis.

Methods

Different databases were searched for full-text publication based on inclusion and exclusion criteria. For data-pooling, fixed-effect model was applied if heterogeneity wasn’t detected. Otherwise, random-effect model was adopted. Heterogeneity was detected by I squire (I2) test. All results of analysis were illustrated as forest plots. Publication bias was assessed using the Begg’s adjusted rank correlation test. Standard mean difference (SMD) was calculated in continuous variables. Pooled hazard ratio or odds ratio was calculated in catergorical variables.

Results

Seventeen clinical studies were finally included. Hepatic portal hemodynamic parameters were improved in statin users for a short-term response. For a long-term follow-up, statin treatment surprisingly decreased mortality rate (HR = 0.782, 95% CI: 0.718–0.846, I2 > 50%) and lower the occurrence of hepatocellular carcinoma (HR = 0.75, 95% CI: 0.64–0.86, I2 > 50%) in liver cirrhosis. Statin seemed not to decrease the risk of esophageal variceal bleeding and spontaneous bacterial peritonitis. However, statin was proved to decrease the risk of hepatic encephalopathy and ascites. Incidence of drug related adverse events didn’t increase in statin users. Dose-dependent effects of statin on hepatocellular carcinoma development, decompensated cirrhosis events occurrence, and liver cirrhosis progression.

Conclusion

Statin influenced parameters of hepatic portal vessel pressure in short-term treatment. Prognosis of liver cirrhosis benefited from statin treatment in long term follow-up. The efficacy and safety of statin in liver cirrhosis treatment is confirmed. To date, similar study is hardly seen before.
Appendix
Available only for authorised users
Literature
1.
go back to reference Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet (London, England). 2014;383(9930):1749–61.CrossRef Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet (London, England). 2014;383(9930):1749–61.CrossRef
2.
go back to reference 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(1):217–31.PubMedCrossRef 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(1):217–31.PubMedCrossRef
3.
go back to reference D'Amico G, Morabito A, D'Amico M, Pasta L, Malizia G, Rebora P, et al. Clinical states of cirrhosis and competing risks. J Hepatol. 2018;68(3):563–76.PubMedCrossRef D'Amico G, Morabito A, D'Amico M, Pasta L, Malizia G, Rebora P, et al. Clinical states of cirrhosis and competing risks. J Hepatol. 2018;68(3):563–76.PubMedCrossRef
4.
go back to reference Younossi Z, Henry L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology. 2016;150(8):1778–85.PubMedCrossRef Younossi Z, Henry L. Contribution of alcoholic and nonalcoholic fatty liver disease to the burden of liver-related morbidity and mortality. Gastroenterology. 2016;150(8):1778–85.PubMedCrossRef
5.
go back to reference Schuppan D, Afdhal NH, et al. Lancet (London, England). 2008;371(9615):838–51.CrossRef Schuppan D, Afdhal NH, et al. Lancet (London, England). 2008;371(9615):838–51.CrossRef
6.
go back to reference Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US preventive services task force. JAMA. 2016;316(19):2008–24.PubMedCrossRef Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: evidence report and systematic review for the US preventive services task force. JAMA. 2016;316(19):2008–24.PubMedCrossRef
8.
go back to reference Arab JP, Shah VH. Statins and portal hypertension: A tale of two models. Hepatology (Baltimore, Md). 2016;63(6):2044–7.CrossRef Arab JP, Shah VH. Statins and portal hypertension: A tale of two models. Hepatology (Baltimore, Md). 2016;63(6):2044–7.CrossRef
9.
go back to reference Meireles CZ, Pasarin M, Lozano JJ, Garcia-Caldero H, Gracia-Sancho J, Garcia-Pagan JC, et al. Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation. Shock (Augusta, Ga). 2017;47(3):370–7.CrossRef Meireles CZ, Pasarin M, Lozano JJ, Garcia-Caldero H, Gracia-Sancho J, Garcia-Pagan JC, et al. Simvastatin Attenuates Liver Injury in Rodents with Biliary Cirrhosis Submitted to Hemorrhage/Resuscitation. Shock (Augusta, Ga). 2017;47(3):370–7.CrossRef
10.
go back to reference Tripathi DM, Vilaseca M, Lafoz E, Garcia-Caldero H, Viegas Haute G, Fernandez-Iglesias A, et al. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension. Gastroenterology. 2018;155(5):1564–77.PubMedCrossRef Tripathi DM, Vilaseca M, Lafoz E, Garcia-Caldero H, Viegas Haute G, Fernandez-Iglesias A, et al. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension. Gastroenterology. 2018;155(5):1564–77.PubMedCrossRef
11.
go back to reference Vargas JI, Arrese M, Shah VH, Arab JP. Use of statins in patients with chronic liver disease and cirrhosis: current views and prospects. Curr Gastroenterol Rep. 2017;19(9):43.PubMedPubMedCentralCrossRef Vargas JI, Arrese M, Shah VH, Arab JP. Use of statins in patients with chronic liver disease and cirrhosis: current views and prospects. Curr Gastroenterol Rep. 2017;19(9):43.PubMedPubMedCentralCrossRef
12.
go back to reference 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(10):1495–505.PubMedCrossRef 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(10):1495–505.PubMedCrossRef
13.
go back to reference 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(10):1521–30.e8.PubMedPubMedCentralCrossRef 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(10):1521–30.e8.PubMedPubMedCentralCrossRef
14.
go back to reference Pose E, Trebicka J, Mookerjee RP, Angeli P, Gines P. Statins: old drugs as new therapy for liver diseases? J Hepatol. 2019;70(1):194–202.PubMedCrossRef Pose E, Trebicka J, Mookerjee RP, Angeli P, Gines P. Statins: old drugs as new therapy for liver diseases? J Hepatol. 2019;70(1):194–202.PubMedCrossRef
15.
go back to reference Kasia C, Scaglione SJ. Patients with chronic liver disease/cirrhosis should not take statin medications. Clin Liver Dis. 2019;13(4):106–10.CrossRef Kasia C, Scaglione SJ. Patients with chronic liver disease/cirrhosis should not take statin medications. Clin Liver Dis. 2019;13(4):106–10.CrossRef
16.
go back to reference Unger LW, Forstner B, Schneglberger S, Muckenhuber M, Eigenbauer E, Bauer D, et al. Guideline-conform statin use reduces overall mortality in patients with compensated liver disease. Sci Rep. 2019;9(1):11674.PubMedPubMedCentralCrossRef Unger LW, Forstner B, Schneglberger S, Muckenhuber M, Eigenbauer E, Bauer D, et al. Guideline-conform statin use reduces overall mortality in patients with compensated liver disease. Sci Rep. 2019;9(1):11674.PubMedPubMedCentralCrossRef
17.
go back to reference Patel SS, Guzman LA, Lin FP, Pence T, Reichman T, John B, et al. Utilization of aspirin and statin in management of coronary artery disease in patients with cirrhosis undergoing liver transplant evaluation. Liver Transpl. 2018;24(7):872–80.PubMedCrossRef Patel SS, Guzman LA, Lin FP, Pence T, Reichman T, John B, et al. Utilization of aspirin and statin in management of coronary artery disease in patients with cirrhosis undergoing liver transplant evaluation. Liver Transpl. 2018;24(7):872–80.PubMedCrossRef
18.
go back to reference Sigler MA, Congdon L, Edwards KL. An evidence-based review of statin use in patients with nonalcoholic fatty liver disease. Clin Med Insights Gastroenterol. 2018;11:1179552218787502.PubMedPubMedCentralCrossRef Sigler MA, Congdon L, Edwards KL. An evidence-based review of statin use in patients with nonalcoholic fatty liver disease. Clin Med Insights Gastroenterol. 2018;11:1179552218787502.PubMedPubMedCentralCrossRef
19.
go back to reference Wright AP, Adusumalli S, Corey KE. Statin therapy in patients with cirrhosis. Frontline Gastroenterol. 2015;6(4):255–61.PubMedCrossRef Wright AP, Adusumalli S, Corey KE. Statin therapy in patients with cirrhosis. Frontline Gastroenterol. 2015;6(4):255–61.PubMedCrossRef
21.
go back to reference 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. Gastroenterol. 2009;136(5):1651–8.CrossRef 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. Gastroenterol. 2009;136(5):1651–8.CrossRef
22.
go back to reference 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. Gastroenterol. 2016;150(5):1160–70.e3.CrossRef 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. Gastroenterol. 2016;150(5):1160–70.e3.CrossRef
23.
go back to reference 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(7):673–80.PubMedCrossRef 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(7):673–80.PubMedCrossRef
24.
go back to reference 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(1):54–9.PubMedCrossRef 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(1):54–9.PubMedCrossRef
25.
go back to reference 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 (Baltimore, Md). 2017;66(3):896–907.CrossRef 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 (Baltimore, Md). 2017;66(3):896–907.CrossRef
26.
go back to reference Elwan N, Salah R, Hamisa M, Shady E, Hawash N, Abd-Elsalam S. Evaluation of portal pressure by doppler ultrasound in patients with cirrhosis before and after simvastatin administration - a randomized controlled trial. F1000Research. 2018;7:256.PubMedPubMedCentralCrossRef Elwan N, Salah R, Hamisa M, Shady E, Hawash N, Abd-Elsalam S. Evaluation of portal pressure by doppler ultrasound in patients with cirrhosis before and after simvastatin administration - a randomized controlled trial. F1000Research. 2018;7:256.PubMedPubMedCentralCrossRef
27.
go back to reference Huang YW, Lee CL, Yang SS, Fu SC, Chen YY, Wang TC, et al. Statins reduce the risk of cirrhosis and its Decompensation in chronic hepatitis B patients: a Nationwide cohort study. Am J Gastroenterol. 2017;111(7):976.CrossRef Huang YW, Lee CL, Yang SS, Fu SC, Chen YY, Wang TC, et al. Statins reduce the risk of cirrhosis and its Decompensation in chronic hepatitis B patients: a Nationwide cohort study. Am J Gastroenterol. 2017;111(7):976.CrossRef
28.
go back to reference Kaplan DE, Serper MA, Mehta R, Fox R, John B, Aytaman A, et al. Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis. Gastroenterology. 2019;156(6):1693–706.e12.PubMedCrossRef Kaplan DE, Serper MA, Mehta R, Fox R, John B, Aytaman A, et al. Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis. Gastroenterology. 2019;156(6):1693–706.e12.PubMedCrossRef
29.
go back to reference Kim G, Jang SY, Nam CM, Kang ES. Statin use and the risk of hepatocellular carcinoma in patients at high risk: a nationwide nested case-control study. J Hepatol. 2018;68(3):476–84.PubMedCrossRef Kim G, Jang SY, Nam CM, Kang ES. Statin use and the risk of hepatocellular carcinoma in patients at high risk: a nationwide nested case-control study. J Hepatol. 2018;68(3):476–84.PubMedCrossRef
30.
go back to reference Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci. 2014;59(8):1958–65.PubMedCrossRef Kumar S, Grace ND, Qamar AA. Statin use in patients with cirrhosis: a retrospective cohort study. Dig Dis Sci. 2014;59(8):1958–65.PubMedCrossRef
31.
go back to reference 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(2):430–40.e1.PubMedCrossRef 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(2):430–40.e1.PubMedCrossRef
32.
go back to reference 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. Dig Liver Dis. 2015;47(11):957–63.PubMedCrossRef 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. Dig Liver Dis. 2015;47(11):957–63.PubMedCrossRef
33.
go back to reference Simon TG, Bonilla H, Yan P, Chung RT, Butt AA. Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. Hepatology (Baltimore, Md). 2016;64(1):47–57.CrossRef Simon TG, Bonilla H, Yan P, Chung RT, Butt AA. Atorvastatin and fluvastatin are associated with dose-dependent reductions in cirrhosis and hepatocellular carcinoma, among patients with hepatitis C virus: Results from ERCHIVES. Hepatology (Baltimore, Md). 2016;64(1):47–57.CrossRef
34.
go back to reference Simon TG, King LY, Zheng H, Chung RT. Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C. J Hepatol. 2015;62(1):18–23.PubMedCrossRef Simon TG, King LY, Zheng H, Chung RT. Statin use is associated with a reduced risk of fibrosis progression in chronic hepatitis C. J Hepatol. 2015;62(1):18–23.PubMedCrossRef
35.
go back to reference Wani ZA, Mohapatra S, Khan AA, Mohapatra A, Yatoo GN. Addition of simvastatin to carvedilol non responders: a new pharmacological therapy for treatment of portal hypertension. World J Hepatol. 2017;9(5):270–7.PubMedPubMedCentralCrossRef Wani ZA, Mohapatra S, Khan AA, Mohapatra A, Yatoo GN. Addition of simvastatin to carvedilol non responders: a new pharmacological therapy for treatment of portal hypertension. World J Hepatol. 2017;9(5):270–7.PubMedPubMedCentralCrossRef
36.
go back to reference Wong JC, Chan HL, Tse YK, Yip TC, Wong VW, Wong GL. Statins reduce the risk of liver decompensation and death in chronic viral hepatitis: a propensity score weighted landmark analysis. Aliment Pharmacol Ther. 2017;46(10):1001–10.PubMedCrossRef Wong JC, Chan HL, Tse YK, Yip TC, Wong VW, Wong GL. Statins reduce the risk of liver decompensation and death in chronic viral hepatitis: a propensity score weighted landmark analysis. Aliment Pharmacol Ther. 2017;46(10):1001–10.PubMedCrossRef
37.
go back to reference Yang YH, Chen WC, Tsan YT, Chen MJ, Shih WT, Tsai YH, et al. Statin use and the risk of cirrhosis development in patients with hepatitis C virus infection. J Hepatol. 2015;63(5):1111–7.PubMedCrossRef Yang YH, Chen WC, Tsan YT, Chen MJ, Shih WT, Tsai YH, et al. Statin use and the risk of cirrhosis development in patients with hepatitis C virus infection. J Hepatol. 2015;63(5):1111–7.PubMedCrossRef
38.
go back to reference Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ (Clinical research ed). 2015;350:g7647. Shamseer L, Moher D, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ (Clinical research ed). 2015;350:g7647.
39.
go back to reference Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet (London, England). 2019;393(10170):407–15.CrossRef Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet (London, England). 2019;393(10170):407–15.CrossRef
40.
go back to reference Wan S, Huang C, Zhu X. Systematic review with a meta-analysis: clinical effects of statins on the reduction of portal hypertension and variceal haemorrhage in cirrhotic patients. BMJ Open. 2019;9(7):e030038.PubMedPubMedCentralCrossRef Wan S, Huang C, Zhu X. Systematic review with a meta-analysis: clinical effects of statins on the reduction of portal hypertension and variceal haemorrhage in cirrhotic patients. BMJ Open. 2019;9(7):e030038.PubMedPubMedCentralCrossRef
41.
go back to reference Choi HD, Chae SM. Comparison of efficacy and safety of combination therapy with statins and omega-3 fatty acids versus statin monotherapy in patients with dyslipidemia: a systematic review and meta-analysis. Medicine. 2018;97(50):e13593.PubMedPubMedCentralCrossRef Choi HD, Chae SM. Comparison of efficacy and safety of combination therapy with statins and omega-3 fatty acids versus statin monotherapy in patients with dyslipidemia: a systematic review and meta-analysis. Medicine. 2018;97(50):e13593.PubMedPubMedCentralCrossRef
42.
go back to reference He Y, Li X, Gasevic D, Brunt E, McLachlan F, Millenson M, et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials. Ann Intern Med. 2018;169(8):543–53.PubMedCrossRef He Y, Li X, Gasevic D, Brunt E, McLachlan F, Millenson M, et al. Statins and multiple noncardiovascular outcomes: umbrella review of meta-analyses of observational studies and randomized controlled trials. Ann Intern Med. 2018;169(8):543–53.PubMedCrossRef
43.
go back to reference 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(5):533–42.PubMedCrossRef 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(5):533–42.PubMedCrossRef
44.
go back to reference Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6(4):390–9.PubMedCrossRef Naci H, Brugts J, Ades T. Comparative tolerability and harms of individual statins: a study-level network meta-analysis of 246 955 participants from 135 randomized, controlled trials. Circ Cardiovasc Qual Outcomes. 2013;6(4):390–9.PubMedCrossRef
45.
go back to reference Ascione A, Fontanella L, Imparato M, Rinaldi L, De Luca M. Mortality from cirrhosis and hepatocellular carcinoma in Western Europe over the last 40 years. Liver Int. 2017;37(8):1193–201.PubMedCrossRef Ascione A, Fontanella L, Imparato M, Rinaldi L, De Luca M. Mortality from cirrhosis and hepatocellular carcinoma in Western Europe over the last 40 years. Liver Int. 2017;37(8):1193–201.PubMedCrossRef
46.
go back to reference Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet (London, England). 2003;362(9399):1907–17.CrossRef Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet (London, England). 2003;362(9399):1907–17.CrossRef
47.
go back to reference Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–410.PubMedCrossRef Thompson PD, Panza G, Zaleski A, Taylor B. Statin-associated side effects. J Am Coll Cardiol. 2016;67(20):2395–410.PubMedCrossRef
48.
go back to reference Baspinar O, Bayram F, Korkmaz S, Aksu M, Kocer D, Dizdar OS, et al. The effects of statin treatment on adrenal and sexual function and nitric oxide levels in hypercholesterolemic male patients treated with a statin. J Clin Lipidol. 2016;10(6):1452–61.PubMedCrossRef Baspinar O, Bayram F, Korkmaz S, Aksu M, Kocer D, Dizdar OS, et al. The effects of statin treatment on adrenal and sexual function and nitric oxide levels in hypercholesterolemic male patients treated with a statin. J Clin Lipidol. 2016;10(6):1452–61.PubMedCrossRef
49.
go back to reference Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–37 37a-37d.PubMedCrossRef Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J. 2012;33(7):829–37 37a-37d.PubMedCrossRef
50.
go back to reference Vincenzo LM, Marcos P, Meireles CZ, Rosa M, Aina RV, Diana H, et al. Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction. Hepatology (Baltimore, Md). 2013;57(3):1172–81.CrossRef Vincenzo LM, Marcos P, Meireles CZ, Rosa M, Aina RV, Diana H, et al. Effects of simvastatin administration on rodents with lipopolysaccharide-induced liver microvascular dysfunction. Hepatology (Baltimore, Md). 2013;57(3):1172–81.CrossRef
51.
go back to reference Trocha M, Merwid-Lad A, Szuba A, Chlebda E, Piesniewska M, Sozanski T, et al. Effect of simvastatin on nitric oxide synthases (eNOS, iNOS) and arginine and its derivatives (ADMA, SDMA) in ischemia/reperfusion injury in rat liver. Pharmacol Rep. 2010;62(2):343–51.PubMedCrossRef Trocha M, Merwid-Lad A, Szuba A, Chlebda E, Piesniewska M, Sozanski T, et al. Effect of simvastatin on nitric oxide synthases (eNOS, iNOS) and arginine and its derivatives (ADMA, SDMA) in ischemia/reperfusion injury in rat liver. Pharmacol Rep. 2010;62(2):343–51.PubMedCrossRef
52.
go back to reference Zafra C, Abraldes JG, Turnes J, Berzigotti A, Fernandez M, Garca-Pagan JC, et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004;126(3):749–55.PubMedCrossRef Zafra C, Abraldes JG, Turnes J, Berzigotti A, Fernandez M, Garca-Pagan JC, et al. Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis. Gastroenterology. 2004;126(3):749–55.PubMedCrossRef
53.
go back to reference Costa S, Reina-Couto M, Albino-Teixeira A, Sousa T. Statins and oxidative stress in chronic heart failure. Rev Port Cardiol. 2016;35(1):41–57.PubMedCrossRef Costa S, Reina-Couto M, Albino-Teixeira A, Sousa T. Statins and oxidative stress in chronic heart failure. Rev Port Cardiol. 2016;35(1):41–57.PubMedCrossRef
54.
go back to reference Lee SH, Choi NY, Yu HJ, Park J, Choi H, Lee KY, et al. Atorvastatin protects NSC-34 motor neurons against oxidative stress by activating PI3K, ERK and free radical scavenging. Mol Neurobiol. 2016;53(1):695–705.PubMedCrossRef Lee SH, Choi NY, Yu HJ, Park J, Choi H, Lee KY, et al. Atorvastatin protects NSC-34 motor neurons against oxidative stress by activating PI3K, ERK and free radical scavenging. Mol Neurobiol. 2016;53(1):695–705.PubMedCrossRef
55.
go back to reference Athyros VG, Alexandrides TK, Bilianou H, Cholongitas E, Doumas M, Ganotakis ES, et al. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An expert panel statement. Metab Clin Exp. 2017;71:17–32.PubMedCrossRef Athyros VG, Alexandrides TK, Bilianou H, Cholongitas E, Doumas M, Ganotakis ES, et al. The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An expert panel statement. Metab Clin Exp. 2017;71:17–32.PubMedCrossRef
56.
go back to reference Schierwagen R, Uschner FE, Magdaleno F, Klein S, Trebicka J. Rationale for the use of statins in liver disease. Am J Physiol Gastrointest Liver Physiol. 2017;312(5):G407–g12.PubMedCrossRef Schierwagen R, Uschner FE, Magdaleno F, Klein S, Trebicka J. Rationale for the use of statins in liver disease. Am J Physiol Gastrointest Liver Physiol. 2017;312(5):G407–g12.PubMedCrossRef
57.
go back to reference Chen Z, Yu R, Xiong Y, Du F, Zhu S. A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease. Lipids Health Dis. 2017;16(1):203.PubMedPubMedCentralCrossRef Chen Z, Yu R, Xiong Y, Du F, Zhu S. A vicious circle between insulin resistance and inflammation in nonalcoholic fatty liver disease. Lipids Health Dis. 2017;16(1):203.PubMedPubMedCentralCrossRef
58.
go back to reference Franceschini L, Realdon S, Marcolongo M, Mirandola S, Bortoletto G, Alberti A. Reciprocal interference between insulin and interferon-alpha signaling in hepatic cells: a vicious circle of clinical significance? Hepatology (Baltimore, Md). 2011;54(2):484–94.CrossRef Franceschini L, Realdon S, Marcolongo M, Mirandola S, Bortoletto G, Alberti A. Reciprocal interference between insulin and interferon-alpha signaling in hepatic cells: a vicious circle of clinical significance? Hepatology (Baltimore, Md). 2011;54(2):484–94.CrossRef
59.
go back to reference Zhao TY, Su LP, Ma CY, Zhai XH, Duan ZJ, Zhu Y, et al. IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats. BMC Gastroenterol. 2015;15:77.PubMedPubMedCentralCrossRef Zhao TY, Su LP, Ma CY, Zhai XH, Duan ZJ, Zhu Y, et al. IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats. BMC Gastroenterol. 2015;15:77.PubMedPubMedCentralCrossRef
60.
go back to reference Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5):S35–50.PubMedCrossRef Fattovich G, Stroffolini T, Zagni I, Donato F. Hepatocellular carcinoma in cirrhosis: incidence and risk factors. Gastroenterology. 2004;127(5):S35–50.PubMedCrossRef
61.
go back to reference Barbarash O, Gruzdeva O, Uchasova E, Belik E, Dyleva Y, Karetnikova V. Dose-dependent effects of atorvastatin on myocardial infarction. Drug Des Devel Ther. 2015;9:3361–8.PubMedPubMedCentral Barbarash O, Gruzdeva O, Uchasova E, Belik E, Dyleva Y, Karetnikova V. Dose-dependent effects of atorvastatin on myocardial infarction. Drug Des Devel Ther. 2015;9:3361–8.PubMedPubMedCentral
62.
go back to reference Henein M, Granasen G, Wiklund U, Schmermund A, Guerci A, Erbel R, et al. High dose and long-term statin therapy accelerate coronary artery calcification. Int J Cardiol. 2015;184:581–6.PubMedCrossRef Henein M, Granasen G, Wiklund U, Schmermund A, Guerci A, Erbel R, et al. High dose and long-term statin therapy accelerate coronary artery calcification. Int J Cardiol. 2015;184:581–6.PubMedCrossRef
Metadata
Title
Comprehensive evaluation of effects and safety of statin on the progression of liver cirrhosis: a systematic review and meta-analysis
Authors
Yue Gu
Xueqin Yang
Hang Liang
Deli Li
Publication date
01-12-2019

Other articles of this Issue 1/2019

BMC Gastroenterology 1/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.