Statins and Angiotensin‐Converting Enzyme Inhibitors are Associated with Reduced Mortality and Morbidity in Chronic Liver Disease

Abstract

Liver fibrosis is a common response to many chronic liver diseases. The aim of our study was to explore whether pharmacotherapy for concurrent diseases affects overall mortality, liver-related mortality and liver-related morbidity in patients with chronic liver disease. We performed a register-based cohort study of all patients with a first-time diagnosis of chronic liver disease between 2005 and 2012 in Sweden (n = 70 546). Data from the Patient Register, the Prescribed Drug Register and the Death Certificate Register were linked. We studied whether the use of statins, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and antibiotics affected the risk of total mortality, liver-specific mortality and morbidity. We found a reduction in mortality risk for statin users (n = 11,245) with hazard ratios from 0.57 (95% CI: 0.32-0.99) for patients with autoimmune hepatitis to 0.84 (95% CI: 0.75-0.95) for patients with alcoholic liver disease. There was a significantly reduced liver-related mortality for patients with alcoholic liver disease who used angiotensin-converting enzyme inhibitors, 0.85 (95% CI: 0.65-0.96). There were increased overall mortality risks for antibiotic users (n = 44,572), with hazard ratios up to 1.67 (95% CI, 1.55-1.80) for viral hepatitis. Statin use was associated with decreased risks of liver-specific mortality and morbidity, and reduced total mortality foremost among patients with alcoholic liver disease. Angiotensin -converting enzyme inhibitors was associated with reduced liver-related mortality among patients with alcoholic liver disease.

Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis

“…This was most notable among statin-naïve new initiators, the group most often studied in population-level cohorts of the effect of statins on survival in cirrhosis or chronic liver disease. 15,[17][18][19]45 We examined 2 distinct statin-exposed cohorts, existing users and new initiators, to assess the magnitude of decrease of mortality associated with each year of cumulative statin exposure, finding highly consistent effect sizes (HR 0.913-0.920) after adjusting for hyperlipidemia. These estimates suggest a much more modest impact of statin exposure than previous retrospective studies (HR 0.45 in meta-analysis).…”

“…46 We postulate that the primary reasons for this difference include (1) adjustment for hyperlipidemia in our models and (2) treatment of statin exposure as a time-dependent covariate 47 rather than solely as a dichotomized variable with 28-to 90-day exposure windows as in previous studies. 15,[17][18][19] The use of dichotomized exposure variables cannot account for the impact of long-term cumulative statin exposure, which could decrease systemic inflammation and fibrosis. 47 A third potential reason for the smaller estimate of effect size in the present study is the use of comprehensive propensity matching using time-updated covariates, 48 which was highly effective in risk-set matching new initiators with non-initiators.…”

“…11,12 Multiple, mostly retrospective, studies have demonstrated that statins are not only safe for use, but that patients with HCV and HBV infection and cirrhosis exposed to statins have lower risks of liver cancer (hazard ratio [HR] w0.42), infections, decompensation (HR w0.55), and death. [13][14][15][16][17][18][19] Despite these potential benefits, statins remain underused in patients with cirrhosis owing to concerns for liver-related toxicity. 20 Prior studies investigating the impact of statins on health outcomes in cirrhosis have certain limitations.…”

Update on New Aspects of the Renin-Angiotensin System in Hepatic Fibrosis and Portal Hypertension: Implications for Novel Therapeutic Options

“…The patients with no hypertension included in the Group 3 showed the lowest mean fibrosis score supporting the theory that hypertension and activation of RAS contributes to fibrosis progression. Another registerbased cohort study of patients (n = 70,546) with a first-time diagnosis of chronic liver disease between 2005 and 2012 in Sweden revealed a marked reduction in liver-related mortality among patients with alcoholic liver disease who received ACE inhibitors [53].…”

Reversing Epigenetic Alterations Caused by Alcohol: A Promising Therapeutic Direction for Alcoholic Liver Disease

“…Statins are widely used in the treatment of hyperlipemia and coronary artery disease, which are also closely related to lipid metabolism, oxidative stress, and inflammation (Chen et al., ; Zheng et al., ). A recent study has reported that statins are associated with reduced total mortality among patients with ALD (Stokkeland et al., ). However, the underlying mechanism is unknown.…”