Background/Purpose: Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease characterized by chronic destructive arthritis and extra-articular involvement. Prior studies showed patients with RA had a high prevalence of NAFLD (35.2% in men with RA and 22.2% in women with RA). Lim et al. suggested that hydroxychloroquine (HCQ) may decrease the risk of NAFLD¹. The National Health Insurance Research Database (NHIRD) in Taiwan provided nationwide, population-based claim data to facilitate a longitudinal epidemiologic study.

The aim of the study was to assess the association between HCQ and incident NAFLD in a nationwide RA cohort.

Methods: Using the 2000–2020 NHIRD, we identified 41,791 newly-diagnosed RA patients from 2002 to 2020. After excluding patients with diagnoses of liver diseases (acute/subacute necrosis of liver, chronic liver disease, live abscess/sequelae of chronic liver disease, other disorders of liver, hepatitis B, hepatitis C, alcohol related disorders, alcoholic liver disease) on or before the RA diagnosis date (n = 16,223 patients) and patients with missing data of residence of insured amount (n = 4,110), we included 21,458 patients with RA. A time-varying multivariable Cox regression model was applied to estimate the adjusted hazard ratios (aHRs) with 95% confidence interval (CIs) for the association of NAFLD with the use of HCQ after adjusting potential confounders. Subgroup analyses were conducted based on age (≤50, >50 years) and sex.

Results: The mean ± standard deviation (SD) age was 51.9 ± 14.2 years, and the female-to-male ratio was 3.2. 399 (1.86%) patients developed NAFLD during a mean follow-up period of 8.4 years, with an incidence rate of 2.21 x 10^-3. Multivariable time-dependent Cox regression analyses showed that HCQ use was associated with a lower risk of NAFLD (aHR, 0.75; 95% CI, 0.60–0.93; p = 0.007). Other significant predictors for the risk of NAFLD included obesity (aHR, 4.63; 95% CI, 1.47–14.59; p = 0.009), defined daily dose (DDD) of NSAID (per incremental DDD: aHR, 1.03; 95% CI, 1.02–1.05; p < 0.001), prednisolone (Pd) equivalent dose > 5 mg/day (reference: without Pd use; aHR, 2.4; 95% CI, 1.86–3.10; p < 0.001) and Pd equivalent dose ≤5 mg/day (reference: without Pd use; aHR, 0.53; 95% CI, 0.40–0.72; p < 0.001). The association between HCQ and NALFD risk was consistent in patients aged ≤50 years and female patients with RA.

Conclusion: This study revealed that using HCQ was significantly associated with a lower risk of NAFLD, particularly in RA patients aged ≤50 years and in female RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/hydroxychloroquine-is-associated-with-a-decreased-risk-of-non-alcoholic-fatty-liver-disease-in-patients-with-rheumatoid-arthritis-a-population-based-cohort-study/