Daily Aspirin May Lower Risk for Fatty Liver Progression

Veronica Hackethal, MD

May 17, 2019

Taking daily aspirin may prevent progression of nonalcoholic fatty liver disease (NAFLD) to liver fibrosis and nonalcoholic steatopepatitis (NASH), according to a study published online May 8 in Clinical Gastroenterology and Hepatology.

"Our study was the first prospective study of its kind to demonstrate that aspirin is associated with less severe liver histology among patients with NAFLD, and that taking aspirin on a daily basis was associated with reduced risk of developing liver fibrosis over time," Tracey Simon, MD, from Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

Until now, only two cross-sectional studies have evaluated the issue in humans, although results from rodent studies have suggested that aspirin may prevent progression to fibrosis in NAFLD.

While findings from the new study may not have direct clinical implications right now, Simon said they have "a lot of potential" to impact patient care in coming years.

"If these findings are validated in further research I think this could be very important for future care of patients with fatty liver disease, for whom we don't have any good preventive drugs to slow the rate of progression to NASH and fibrosis," she said.

Simon stressed the importance of continued effort to identify drug targets and underlying modifiable risk factors to prevent NAFLD progression, as the incidence and prevalence of NAFLD are accelerating dramatically in the United States.

Currently, about 50 million Americans have NAFLD, which is caused by fat accumulation in the organ. Up to 25% of individuals with NAFLD progress to liver fibrosis and are at risk for cirrhosis, liver cancer, and death, according to the authors.

While evidence no longer supports the use of daily aspirin for primary prevention of cardiovascular disease, these results raise the question whether providers should prescribe aspirin to prevent progression to NASH in patients with NAFLD.

Simon said that it's too early to answer that question.

"To my mind, the most important thing that our study could do is promote further research into this area to try and better characterize the role of aspirin for preventing fibrosis progression or preventing the development of NASH. With further research perhaps such recommendations could come in the future, but we're not there quite yet," she said.

The prospective study included 361 adults with biopsy-confirmed NAFLD who were enrolled in the Massachusetts General Hospital NAFLD Repository between 2006 and 2015. Among participants, 151 were already taking daily aspirin at the start of the study, mostly (54%) for primary cardiovascular disease prevention. Median duration of aspirin use at enrolment was 2.5 years.

Researchers confirmed NAFLD diagnoses through blinded medical record review. A blinded pathologist also assessed baseline liver biopsies.

Researchers examined participants every 3-12 months, according to clinical standards of care. They monitored progression to fibrosis using three validated noninvasive indices of liver fibrosis (the Fibrosis-4, NAFLD fibrosis score, and aspartate aminotransferase-to-platelet ratio indices). Participants with cirrhosis had semiannual ultrasound screening for liver cancer.  

Median follow-up was 7.4 years, and all participants completed the study.

Researchers adjusted cross-sectional analyses for age, sex, race/ethnicity, body mass index, diabetes, hypertension, hyperlipidemia, smoking, coronary artery disease, and statin and metformin use. Longitudinal results analyses were adjusted for these variables as well as for biopsy year and number of follow-up visits.

At the start of the study, daily aspirin use was linked to 46% lower odds for prevalent fibrosis compared with nonregular aspirin use (adjusted odds ratio, 0.54; 95% confidence interval [CI], .31 - .82). Participants with longer duration of aspirin use at enrollment had significantly lower odds for fibrosis (P trend = .016). 

Among a subgroup of participants with early-stage NAFLD at enrollment (n = 317), 86 developed advanced fibrosis during the study.

Analyses over time of this subgroup showed that daily aspirin users had significantly lower cumulative incidence of advanced fibrosis (Gray P value < .001) and 37% lower odds developing advanced fibrosis compared with nonregular aspirin users (adjusted hazard ratio [aHR], 0.63; 95% CI, .43 - .85).

Participants with longer duration of daily aspirin use had significantly lower risk of developing fibrosis (P trend  =  .026). Risk decreased with increasing duration of daily aspirin use.

Risk for fibrosis decreased after at least 2 years of daily aspirin use (aHR, 0.64; 95% CI, 0.45 - 0.86), and was lowest after 4 or more years of daily use (aHR, 0.50; 95% CI, 0.35 - 0.73).

The authors mentioned several limitations. Participants self-reported aspirin use, but this bias may have been minimized medical record review and collecting data on aspirin use at follow-up visits. Most participants (about 79%) were white, and relatively few used certain classes of antidiabetic drugs. Also, researchers used noninvasive indices of liver fibrosis, which are not the gold standard. But findings were similar in analyses of patients with follow-up biopsies. Finally, patients with progressive fibrosis could have been advised to avoid aspirin, which could have biased results.

The authors have disclosed no relevant financial relationships.

Clin Gastroenterol Hepatol. Published online May 8, 2019. doi: 10.1016/j.cgh.2019.04.061 Abstract

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