Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease

Abstract

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.

Keywords: Anti-fibrotic; Anti-inflammatory; Chronic Liver Disease; Prevention.

Figure 1.. Cumulative incidence of advanced fibrosis¹ with long-term daily aspirin use², among patients with baseline early-stage NAFLD* (n=317)

Abbreviations: NAFLD, nonalcoholic fatty liver disease; No., number ¹Incident advanced fibrosis was defined by the first recorded Fibrosis-4 (FIB-4) score > 2.67 or NAFLD Fibrosis Score (NFS) > 0.67, or aspartate aminotransferase-to-platelet ratio index (APRI) > 1.0 during study follow-up. Follow-up measurements of each index score was obtained at least annually in all included participants. ²Daily aspirin use was ascertained and verified by trained study staff at enrollment and at each clinical visit. Non-regular aspirin use was defined as less than daily use or non-use of aspirin. This variable was prospectively-updated during study follow-up and modeled as a time-varying exposure.. *Early-stage NAFLD defined as baseline fibrosis stage 0-2 on enrollment liver biopsy, confirmed by a blinded pathologist.