Effects of Hypercholesterolemia and Statin Exposure on Survival in a Large National Cohort of Patients With Cirrhosis.
Kaplan David E,Serper Marina A,Mehta Rajni,Fox Rena,John Binu,Aytaman Ayse,Baytarian Michelle,Hunt Kristel,Albrecht Jeffrey,Njei Basile,Taddei Tamar H,
Gastroenterology
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.
10.1053/j.gastro.2019.01.026
Statins: Old drugs as new therapy for liver diseases?
Pose Elisa,Trebicka Jonel,Mookerjee Rajeshwar P,Angeli Paolo,Ginès Pere
Journal of hepatology
In addition to lowering cholesterol levels, statins have pleiotropic effects, particularly anti-inflammatory, antiangiogenic, and antifibrotic, that may be beneficial in some chronic inflammatory conditions. Statins have only recently been investigated as a potential treatment option in chronic liver diseases because of concerns related to their safety in patients with impaired liver function. A number of experimental studies in animal models of liver diseases have shown that statins decrease hepatic inflammation, fibrogenesis and portal pressure. In addition, retrospective cohort studies in large populations of patients with cirrhosis and pre-cirrhotic conditions have shown that treatment with statins, with the purpose of decreasing high cholesterol levels, was associated with a reduced risk of disease progression, hepatic decompensation, hepatocellular carcinoma development, and death. These beneficial effects persisted after adjustment for disease severity and other potential confounders. Finally, a few randomised controlled trials have shown that treatment with simvastatin decreases portal pressure (two studies) and mortality (one study). Statin treatment was generally well tolerated but a few patients developed severe side effects, particularly rhabdomyolysis. Despite these promising beneficial effects, further randomised controlled trials in large series of patients with hard clinical endpoints should be performed before statins can be recommended for use in clinical practice.
10.1016/j.jhep.2018.07.019
Lipophilic Statins and Risk for Hepatocellular Carcinoma and Death in Patients With Chronic Viral Hepatitis: Results From a Nationwide Swedish Population.
Simon Tracey G,Duberg Ann-Sofi,Aleman Soo,Hagstrom Hannes,Nguyen Long H,Khalili Hamed,Chung Raymond T,Ludvigsson Jonas F
Annals of internal medicine
Background:Whether statin type influences hepatocellular carcinoma (HCC) incidence or mortality in chronic hepatitis B or C virus infection is unknown. Objective:To assess the relationship between lipophilic or hydrophilic statin use and HCC incidence and mortality in a nationwide population with viral hepatitis. Design:Prospective propensity score (PS)-matched cohort. Setting:Swedish registers, 2005 to 2013. Participants:A PS-matched cohort of 16 668 adults (8334 who initiated statin use [6554 lipophilic and 1780 hydrophilic] and 8334 nonusers) among 63 279 eligible adults. Measurements:Time to incident HCC, ascertained from validated registers. Statin use was defined from filled prescriptions as 30 or more cumulative defined daily doses (cDDDs). Results:Compared with matched nonusers, 10-year HCC risk was significantly lower among lipophilic statin users (8.1% vs. 3.3%; absolute risk difference [RD], -4.8 percentage points [95% CI, -6.2 to -3.3 percentage points]; adjusted subdistribution hazard ratio [aHR], 0.56 [CI, 0.41 to 0.79]) but not hydrophilic statin users (8.0% vs. 6.8%; RD, -1.2 percentage points [CI, -2.6 to 0.4 percentage points]; aHR, 0.95 [CI, 0.86 to 1.08]). The inverse association between lipophilic statins and HCC risk seemed to be dose-dependent. Compared with nonusers, 10-year HCC risk was lowest with 600 or more lipophilic statin cDDDs (8.4% vs. 2.5%; RD, -5.9 percentage points [CI, -7.6 to -4.2 percentage points]; aHR, 0.41 [CI, 0.32 to 0.61]), and 10-year mortality was significantly lower among both lipophilic (15.2% vs. 7.3%; RD, -7.9 percentage points [CI, -9.6 to -6.2 percentage points]) and hydrophilic (16.0% vs. 11.5%; RD, -4.5 percentage points [CI, -6.0 to -3.0 percentage points]) statin users. Limitation:Lack of lipid, fibrosis, or HCC surveillance data. Conclusion:In a nationwide viral hepatitis cohort, lipophilic statins were associated with significantly reduced HCC incidence and mortality. An association between hydrophilic statins and reduced risk for HCC was not found. Further research is needed to determine whether lipophilic statin therapy is feasible for prevention of HCC. Primary Funding Source:None.
10.7326/M18-2753
Statin Use and Risk of Cirrhosis and Related Complications in Patients With Chronic Liver Diseases: A Systematic Review and Meta-analysis.
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
BACKGROUND & AIMS:Statins have been variably shown to decrease risk and complications of chronic liver diseases (CLDs). We performed a systematic review and meta-analysis to evaluate the association between statins and risk of cirrhosis and related complications in patients with CLDs. METHODS:Through a systematic literature search up to March 2017, we identified 13 studies (3 randomized trials, 10 cohort studies) in adults with CLDs, reporting the association between statin use and risk of development of cirrhosis, decompensated cirrhosis, improvements in portal hypertension, or mortality. Pooled relative risk (RR) estimates with 95% confidence interval (CIs) were calculated using random effects model. Grading of Recommendations Assessment, Development and Evaluation criteria were used to assess quality of evidence. RESULTS:Among 121,058 patients with CLDs (84.5% with hepatitis C), 46% were exposed to statins. In patients with cirrhosis, statin use was associated with 46% lower risk of hepatic decompensation (4 studies; RR, 0.54; 95% CI, 0.46-0.62; I = 0%; moderate-quality evidence), and 46% lower mortality (5 studies; RR, 0.54; 95% CI, 0.47-0.61; I = 10%; moderate-quality evidence). In patients with CLD without cirrhosis, statin use was associated with a nonsignificant (58% lower) risk of development of cirrhosis or fibrosis progression (5 studies; RR, 0.42; 95% CI, 0.16-1.11; I = 99%; very-low-quality evidence). In 3 randomized controlled trials, statin use was associated with 27% lower risk of variceal bleeding or progression of portal hypertension (hazard ratio, 0.73; 95% CI, 0.59-0.91; I = 0%; moderate-quality evidence). CONCLUSIONS:Based on a systematic review and meta-analysis, statin use is probably associated with lower risk of hepatic decompensation and mortality, and might reduce portal hypertension, in patients with CLDs. Prospective observational studies and randomized controlled trials are needed to confirm this observation.
10.1016/j.cgh.2017.04.039
Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study.
Chang Fu-Ming,Wang Yen-Po,Lang Hui-Chu,Tsai Chia-Fen,Hou Ming-Chih,Lee Fa-Yauh,Lu Ching-Liang
Hepatology (Baltimore, Md.)
Statin use decreases the risk of decompensation and mortality in patients with cirrhosis due to hepatitis C virus (HCV). Whether this beneficial effect can be extended to cirrhosis in the general population or cirrhosis due to other causes, such as hepatitis B virus (HBV) infection or alcohol, remains unknown. Statin use also decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV and HCV infection. It is unclear whether the effect can be observed in patients with pre-existing cirrhosis. The goal of this study was to determine the effect of statin use on rates of decompensation, mortality, and HCC in HBV-, HCV-, and alcohol-related cirrhosis. Patients with cirrhosis were identified from a representative cohort of Taiwan National Health Insurance beneficiaries from 2000 to 2013. Statin users, defined as having a cumulative defined daily dose (cDDD) ≥28, were selected and served as the case cohort. Statin nonusers (<28 cDDD) were matched through propensity scores. The association between statin use and risk of decompensation, mortality, and HCC were estimated. A total of 1350 patients with cirrhosis were enrolled. Among patients with cirrhosis, statin use decreased the risk of decompensation, mortality, and HCC in a dose-dependent manner (P for trend <0.0001, <0.0001, and 0.009, respectively). Regression analysis revealed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.25-0.62) or HCV infection (HR, 0.51; 95% CI, 0.29-0.93). The lowered risk of decompensation was of borderline significance among statin users with alcohol-related cirrhosis (HR, 0.69; 95% CI, 0.45-1.07). CONCLUSION:Statin use decreases the decompensation rate in both HBV- and HCV-related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol-related cirrhosis. (Hepatology 2017;66:896-907).
10.1002/hep.29172
Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C-Related Compensated Cirrhosis.
Mohanty Arpan,Tate Janet P,Garcia-Tsao Guadalupe
Gastroenterology
BACKGROUND & AIMS:Statins decrease portal pressure in patients with cirrhosis and increase survival times of patients who have bled from varices. However, statins can be hepatotoxic. It is important to determine whether long-term statin use will be beneficial or detrimental for patients with cirrhosis because physicians are reluctant to prescribe statins to patients with liver disease. We investigated the effects of statins on decompensation and survival times in patients with compensated cirrhosis. METHODS:We performed a retrospective cohort using the Veteran Affairs Clinical Case Registry, which contains nationwide data from veterans infected with the hepatitis C virus (HCV). We identified patients with compensated cirrhosis from January 1996 through December 2009. Statin use was according to filled prescriptions. Cirrhosis and decompensation were determined from International Classification of Diseases, 9th revision codes, using a validated algorithm. RESULTS:Among 40,512 patients with HCV compensated cirrhosis (98% male; median age, 56 y), 2802 statin users were identified. We developed a propensity score model using variables associated with statin prescription, and new statin users were matched with up to 5 nonusers; 685 statin users were matched with 2062 nonusers. Discrimination of the propensity score model was 0.92. Statin users had a lower risk of decompensation (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.39-0.77) and death (HR, 0.56; 95% CI, 0.46-0.69), compared with nonusers. Findings persisted after adjustment for age, FIB-4 index score, serum level of albumin, model for end-stage liver disease and Child-Turcotte-Pugh scores (HR for decompensation, 0.55; 95% CI, 0.39-0.78), and death (HR, 0.55; 95% CI, 0.45-0.68). CONCLUSIONS:Based on data from the Veteran Affairs Clinical Case Registry, statin use among patients with HCV and compensated cirrhosis is associated with a more than 40% lower risk of cirrhosis decompensation and death. Although statins cannot yet be recommended widely for these patients, their use should not be avoided.
10.1053/j.gastro.2015.10.007