Hydroxychloroquine use predicts lower risk for fatty liver disease in rheumatoid arthritis
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SAN DIEGO — Patients with rheumatoid arthritis who receive hydroxychloroquine demonstrate a lower risk for nonalcoholic fatty liver disease, according to data presented at ACR Convergence 2023.
“We all know that rheumatoid arthritis is an autoimmune rheumatic disease that affects many joints,” Hsin-Hua Chen, MD, PhD, of Taichung Veterans General Hospital, in Taichung City, Tawain, said at a press conference during the meeting. “However, several diseases are also associated with rheumatoid arthritis, such as interstitial lung disease or cardiovascular disease. In recent years, we know that nonalcoholic fatty liver disease is also an important issue, and prior studies show that about 35% and 22% of male and female rheumatoid arthritis patients are also affected by nonalcoholic fatty liver disease.
“[A previous small study] found that in patients with rheumatoid arthritis, the use of hydroxychloroquine is associated with a decrease of nonalcoholic fatty liver disease,” he added.
To examine the link between hydroxychloroquine and nonalcoholic fatty liver disease in patients with RA, Chen and colleagues analyzed data from the 2000 to 2020 National Health Insurance Research Database (NHIRD) in Taiwan. The researchers identified a total of 41,791 patients who had been recently diagnosed with RA from 2002 to 2020. After excluding those with current or prior liver diseases as of the RA diagnosis date, as well as those with missing data, Chen and colleagues included 21,458 patients with RA in the final analysis.
The researchers used a time-varying multivariable Cox regression model to calculate the adjusted HRs for the link between nonalcoholic fatty liver disease and hydroxychloroquine treatment, adjusting for confounders. Subgroup assessments based on age and sex were also performed. Among the patients included in the final analysis, the mean age was 51.9 years and the female-to-male ratio was 3:2.
In all, 1.86% of the included patients ultimately developed nonalcoholic fatty liver disease during a mean follow-up period of 8.4 years. According to the researchers, hydroxychloroquine treatment was associated with a lower risk for nonalcoholic fatty liver disease (aHR = 0.75; 95% CI, 0.6-0.93). This was consistent in patients aged 50 years and younger and those with female sex.
Additional significant predictors for nonalcoholic fatty liver disease risk included obesity (aHR = 4.63; 95% CI, 1.47-14.59), defined daily dose (DDD) of NSAIDs (aHR = 1.03 per incremental DDD; 95% CI, 1.02-1.05), a prednisolone equivalent dose of more than 5 mg per day, vs. those who did not use prednisolone (aHR = 2.4; 95% CI, 1.86-3.10), and a prednisolone equivalent dose 5 mg per day or less, vs. without prednisolone use (aHR = 0.53; 95% CI, 0.4-0.72).
“Further study is needed to make sure what the underlying mechanism is,” Chen said. “However, currently we can try to use hydroxychloroquine maybe in patients with a higher risk for fatty liver disease, such as those who are obese. We can also try to do further clinical trials by using hydroxychloroquine to see whether it really benefits nonalcoholic fatty liver disease in patients with RA.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
Hydroxychloroquine is an amazing drug. Discovered fortuitously to be effective in rheumatoid arthritis and lupus, it has been found to have multiple beneficial effects in various diseases. Hydroxychloroquine safeguards against thrombotic events, enhances lipid profiles, regulates glucose and prevents renal damage in lupus studies. This collective effect suggests a lowered cardiovascular risk, particularly significant for patients with systemic lupus erythematosus who already face an independent risk factor.
Moreover, hydroxychloroquine has been associated with increased survival rates in SLE. Additionally, the drug demonstrates safety and efficacy in pregnant patients, reducing flares and decreasing the risk for cardiac neonatal lupus.
Now, it appears that hydroxychloroquine lowers the risk for non-alcoholic fatty liver disease (NAFLD), which has a high prevalence in patients with RA. NAFLD and non-alcoholic steatohepatitis have been conditions in which we have no FDA-approved pharmacologic treatment. We recommend a Mediterranean diet but have few other suggestions other than weight loss. The discovery of a lower incidence of NAFLD with hydroxychloroquine in this big-data analysis certainly warrants further study.
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Chen H. Abstract 0396. Presented at: ACR Convergence 2023; Nov. 10-15, 2023; San Diego.
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