Original article
Pancreas, biliary tract, and liver
Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease

https://doi.org/10.1016/j.cgh.2019.04.061Get rights and content

Background & Aims

There are few data from prospective studies on the effects of aspirin on fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

Methods

We performed a prospective cohort study of 361 adults with biopsy-confirmed NAFLD, from 2006 through 2015, examined every 3–12 months for incident advanced fibrosis defined using serial measurements of validated indices (the Fibrosis-4, NAFLD fibrosis score, and aspartate aminotransferase to platelet ratio indices). Histologic analyses of liver biopsies collected at baseline were performed by a blinded pathologist. Information collected at baseline and at each examination included frequency and duration of aspirin and nonsteroidal anti-inflammatory drug (NSAID) use. Using multivariable-adjusted logistic regression, we estimated the association of aspirin use with prevalent steatohepatitis (NASH) and fibrosis. Using multivariable-adjusted Cox proportional hazards modeling, we estimated the association between aspirin use and risk for fibrosis progression.

Results

At enrollment, 151 subjects used aspirin daily. Compared with non-regular use, daily aspirin use was associated with significantly lower odds of NASH (adjusted odds ratio, 0.68; 95% CI, 0.37–0.89) and fibrosis (adjusted odds ratio, 0.54; 95% CI, 0.31–0.82). Among individuals with baseline F0–F2 fibrosis (n = 317), 86 developed advanced fibrosis over 3692 person-years. Daily aspirin users had significantly lower risk for developing incident advanced fibrosis vs non-regular users (adjusted hazard ratio [aHR], 0.63; 95% CI, 0.43–0.85). This relationship appeared to be duration dependent (adjusted P trend=.026), with the greatest benefit found with at least 4 years or more of aspirin use (aHR, 0.50; 95% CI, 0.35–0.73). Conversely, use of nonaspirin NSAIDs was not associated with risk for advanced fibrosis (aHR, 0.93; 95% CI, 0.81–1.05).

Conclusions

In a prospective study of patients with biopsy-proven NAFLD, daily aspirin use was associated with less severe histologic features of NAFLD and NASH, and lower risk for progression to advanced fibrosis with time.

Section snippets

Study Population

The Massachusetts General Hospital NAFLD Repository is a prospective cohort study of adults older than the age of 18 years with biopsy-confirmed NAFLD. All subjects were referred for clinically indicated liver biopsy from community clinics. More than 90% of biopsies were obtained for persistent unexplained elevation of aminotransferases and/or abnormal hepatic imaging suggesting steatosis and/or fibrosis. This study was approved by the Massachusetts General Hospital Institutional Review Board,

Results

Table 1 describes the baseline characteristics of the full study cohort (n = 361). Compared with non-regular users, daily aspirin users were significantly older (mean, 60 ± 9 years vs 48 ± 14 years; P < .0001) and more likely to have diabetes (46% vs 39%, P = .001), coronary artery disease (21% vs 9%, P < .0001), and to be former smokers (39% vs 25%, P = .011). Mean baseline NFS, APRI, and FIB-4 scores were similar between groups (all P > .05). Among daily aspirin users, the median duration of

Discussion

In a well-phenotyped, prospective population with biopsy-proven NAFLD, daily aspirin use was inversely associated with NAFLD histologic severity and with risk for developing incident advanced fibrosis. Importantly, these findings were consistent in women and men and among patients with paired liver biopsies. We also found this inverse relationship to be duration-dependent, such that risk for developing advanced fibrosis was significantly reduced after at least 2 years of daily aspirin use. In

References (30)

  • Y.H. Paik et al.

    Celecoxib induces hepatic stellate cell apoptosis through inhibition of Akt activation and suppresses hepatic fibrosis in rats

    Gut

    (2009)
  • Z.G. Jiang et al.

    Aspirin use is associated with lower indices of liver fibrosis among adults in the United States

    Aliment Pharmacol Ther

    (2016)
  • R.K. Sterling et al.

    Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection

    Hepatology

    (2006)
  • G. Xiao et al.

    Comparison of laboratory tests, ultrasound, or magnetic resonance elastography to detect fibrosis in patients with nonalcoholic fatty liver disease: a meta-analysis

    Hepatology

    (2017)
  • Z.H. Lin et al.

    Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: an updated meta-analysis

    Hepatology

    (2011)
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    Conflicts of interest The authors disclose no conflicts.

    Funding Supported by NIH grant K24DK078772 (R.T.C.), NIH grant K23DK099422 (K.E.C.), NIH grant K24DK098311 (A.T.C.), NCI grant R01 CA137178 (A.T.C.), NIH grant 5P30DK046200-25 (T.G.S.), and NIH grant K23DK122104 (T.G.S.). Dr Chung is a Kevin and Polly Maroni MGH Research Scholar. Dr Chan is a Stuart and Suzanne Steele MGH Research Scholar. T.S. is supported by a Clinical and Translational Research Award by the AASLD Foundation. R.M. is supported by a Pinnacle Research Award from the AASLD Foundation.

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