Taking daily aspirin may help keep nonalcoholic fatty liver disease (NAFLD) from progressing to liver fibrosis and nonalcoholic steatohepatitis (NASH), suggest the results of a prospective study of 361 adults.
Previously, preclinical evidence had linked aspirin to fibrogenesis prevention in fatty liver disease, but this is the first report of a prospective study to do so. Daily aspirin use “was associated with less severe histologic features of NAFLD (nonalcoholic fatty liver disease) at study enrollment and with significantly lower risk for advanced fibrosis over time in a duration-dependent manner,” wrote Tracey G. Simon, MD, MPH, and her associates. Their report is in.
The study comprised 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. At baseline, 151 individuals were already on daily aspirin, usually to reduce the primary (54%) or secondary (30%) risk of cardiovascular disease. Median duration of aspirin use was 2.5 years. After a median 7.4 years of follow-up (which was similar between aspirin users and nonusers), daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% confidence interval, 0.37-0.89) and fibrosis (aOR, 0.54; 95% CI, 0.31-0.82).
The researchers did not find a similar protective effect for nonsteroidal anti-inflammatory drugs (NSAIDs) other than aspirin (adjusted hazard ratio for advanced fibrosis, 0.93; 95% CI, 0.81–1.05). This might be because of differences between how aspirin and nonaspirin NSAIDs affect COX isoforms – aspirin does so irreversibly, while other NSAIDs have a reversible effect, they added. “Nonaspirin NSAIDs also disrupt the intestinal barrier, increasing delivery of proinflammatory cytokines to the liver,” they wrote. “Finally, aspirin uniquely modulates bioactive lipids by stimulating the biosynthesis of pro-resolving mediators and inhibiting proinflammatory lipids, which in turn may prevent progressive liver damage.”
In this study, a single blinded hepatopathologist interpreted baseline liver biopsy specimens, and patients were followed every 3-6 months with clinical examinations and serial calculations of, , and scores. All patients were followed for at least a year. Patients were classified as users of nonaspirin NSAIDs if they reported using an NSAID besides aspirin at least twice weekly, or if they had been prescribed drugs such as ibuprofen, naproxen, ketoprofen, diclofenac, or indomethacin.
In a longitudinal analysis of the 317 patients who had early-stage (F0-2) fibrosis at baseline, 86 developed new-onset advanced fibrosis over a median of 3,692 person-years, the researchers said. In all, 26 individuals developed hepatic decompensation and 18 patients died, including eight from liver-related causes. Importantly, the link between aspirin and decreased risk of fibrosis progression seemed to depend on duration of use (adjusted P trend = .026), with the greatest benefit seen with 4 years or more of use (aHR, 0.50; 95% CI, 0.35-0.73). Although subgroup analyses were limited by lack of power, daily aspirin use was associated with a 36% lower odds of incident advanced fibrosis among the 72 study participants who had paired biopsy samples, even after accounting for the effect of age, sex, baseline fibrosis stage, and time between biopsies (aOR, 0.64; 95% CI, 0.50-0.80).
“Our findings add to the growing literature supporting the potential hepatoprotective effects of aspirin in NAFLD,” the researchers concluded. “Research to uncover the mechanisms by which aspirin might prevent fibrogenesis could help develop urgently needed antifibrotic therapies for NAFLD.”
Funders included the National Institutes of Health and the AASLD Foundation. The investigators reported having no conflicts of interest.
SOURCE: Simon TG et al. .