Antirheumatic drugs and the risk of nonalcoholic fatty liver disease in patients with rheumatoid arthritis: A nationwide, population-based cohort study

Objectives

To assess the association between antirheumatic drugs and of the risk of nonalcoholic fatty liver disease (NAFLD) in a nationwide rheumatoid arthritis (RA) cohort.

Methods

Using claim data from the 2000–2020 National Health Insurance Research Database, we identified 21 457 incident patients with RA from 2002 to 2020 without prior liver diseases. A time-varying multivariable Cox regression model was applied to estimate for the association of NAFLD with the use of antirheumatic drugs after adjusting potential confounders, show as adjusted hazard ratios (aHRs) with 95% confidence interval (CIs). Subgroup analyses were conducted based on age-, sex-, and obesity-related comorbidities.

Results

Multivariable time-dependent Cox regression analyses showed that defined daily dose (DDD) of NSAID (aHR, 1.03; 95% CI: 1.02–1.05) and prednisolone equivalent dose >5 mg/day (aHR, 2.39; 95% CI: 1.85–3.09) were risk factors of NAFLD in patients with RA, while prednisolone equivalent dose ≤5 mg/day (aHR of 0.53; 95% CI: 0.40–0.71) and HCQ use (aHR of 0.75; 95% CI: 0.60–0.93) were associated with a decreased risk of NAFLD. In addition, a history of hospitalizations, number of outpatient visits, age, male, and leflunomide use were associated with the development of NAFLD in some subgroups.

Conclusion

This study reveals that NSAID use and prednisolone equivalent dose >5 mg/day were associated with an increased risk of NAFLD in patients with RA, while the use of HCQ and prednisolone equivalent dose ≤5 mg/day decreased the risk of NAFLD.