Spotlight on statins and chronic liver disease

Recent studies found associations between statin use and decreased risks of severe liver disease and mortality in patients with chronic liver disease.

Two recent studies linked statin use to improved outcomes in patients with chronic liver disease.

The first study found that statin use is associated with a decreased risk of developing severe liver disease in patients with noncirrhotic chronic liver disease. Researchers used liver histopathology data in a nationwide Swedish cohort to identify 3,862 individuals who had noncirrhotic chronic liver disease and statin exposure, defined as a statin prescription filled for 30 or more cumulative daily doses. They matched statin users with 3,862 nonusers with chronic liver disease through direct 1:1 matching followed by propensity score matching. The primary outcome was incident severe liver disease, defined as a composite of cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation/liver-related mortality. Follow-up time accrued from statin exposure or corresponding nonstatin drug prescription and ended with the first record of cirrhosis, HCC, death or liver transplantation, emigration, or end of follow-up on Dec. 31, 2019. Results were published April 28 by Clinical Gastroenterology and Hepatology.

Overall, 45.3% of chronic liver disease patients had nonalcoholic fatty liver disease (NAFLD), 21.9% had alcohol-related liver disease, 17.7% had viral hepatitis, and 15.1% had autoimmune hepatitis. During follow-up, 234 (6.1%) of statin users versus 276 (7.1%) of nonusers developed severe liver disease. Statin use was associated with a decreased risk of developing severe liver disease (hazard ratio [HR], 0.60; 95% CI, 0.48 to 0.74). Statistically significantly lower rates of severe liver disease were seen in patients with alcohol-related liver disease (HR, 0.30; 95% CI, 0.19 to 0.49) and NAFLD (HR, 0.68; 95% CI, 0.45 to 1.00), but not in those with viral hepatitis (HR, 0.76; 95% CI, 0.51 to 1.14) or autoimmune hepatitis (HR, 0.88; 95% CI, 0.48 to 1.58). Statin use was associated with a protective effect in both prefibrosis and fibrosis stages of liver disease. In addition, statin use was associated with lower rates of progression to cirrhosis (HR, 0.62; 95% CI, 0.49 to 0.78), HCC (HR, 0.44; 95% CI, 0.27 to 0.71), and liver-related mortality (HR, 0.55; 95% CI, 0.36 to 0.82). Limitations of the study include the possibility of unmeasured confounding and the inability to account for patient adherence to or discontinuation of statins, the authors noted.

The second study found that higher statin intensity was associated with a reduced risk of death in patients with chronic liver disease and atherosclerotic cardiovascular disease (ASCVD). Researchers conducted the retrospective cohort study using the National Health Information System Database that represents the nationwide population in South Korea. They included adult patients with chronic liver disease and any records of viral hepatitis or liver cirrhosis from 2011 to 2020. They then included patients with ASCVD who underwent coronary intervention or coronary artery bypass graft surgery and assessed statin exposure and intensity during the 30 days after the date of the initial revascularization procedure. The primary outcome was all-cause mortality. Results were published April 17 by the Journal of the American Heart Association.

A total of 10,442 patients were included, 4,927 (47.2%) who were prescribed high-intensity statins and 5,515 (52.8%) who were prescribed low- or moderate-intensity statins during the exposure assessment period. The average follow-up period for all-cause mortality was 2.35 person-years. The cumulative incidence of all-cause mortality in high-intensity users was significantly lower compared with that in low- or moderate-intensity users. Among 731 all-cause deaths, 445 (60.9%) occurred in low- or moderate-intensity statin users (incidence rate, 34.18 per 1,000 person-years; 95% CI, 31.13 to 37.52) and 286 (39.1%) occurred in high-intensity statin users (incidence rate, 26.24 per 1,000 person-years; 95% CI, 23.36 to 29.46). Compared with low- or moderate-intensity statin use, high-intensity use was associated with a decreased risk of all-cause mortality in an unadjusted model (HR, 0.76; 95% CI, 0.65 to 0.88), although the association weakened in a fully adjusted model (HR, 0.84; 95% CI, 0.72 to 0.98). The study did not clearly address the status or condition of chronic liver disease and may have been affected by residual and unmeasured confounders, among other limitations, the authors noted.