Hydroxychloroquine treatment for rheumatoid arthritis may reduce risk of non-alcoholic fatty liver disease

Treating patients with rheumatoid arthritis (RA) with the drug hydroxychloroquine (HCQ) may reduce the risk of non-alcoholic fatty liver disease (NAFLD), which is particularly common in women over 50, according to new findings. younger.1

The findings were presented at the 2023 American College of Rheumatology (ACR) Annual Meeting. The study was led by Hsin-Hua Chen, MD, PhD, and her collaborators at the Veterans General Hospital in Taichung, Taiwan.

RA is a systemic autoimmune inflammatory disease characterized by persistent inflammation of patients’ joints, leading to damage and loss of function. The condition may also affect body organs such as the heart, eyes, and lungs.

Although NAFLD is not a common complication of RA, approximately 35% of men and 22% of women with RA have this disease. It is understood that approximately 75% of overweight people and 90% of severely obese people will develop non-alcoholic fatty liver disease.3

While these statistics about the disease are well known, this study may be noteworthy for rheumatologists given that there are currently no U.S. Food and Drug Administration (FDA)-approved treatments for NAFLD.

For the study, the researchers drew data from Taiwan’s National Health Insurance Research Database on more than 21,000 people between 2000 and 2020, based on previous indications of HCQ’s ability to reduce risk.

The average age of the patients in the database was 51.9 years, and the female-to-male ratio was 3 to 2. We used time-varying, multivariable Cox regression models as a method to estimate adjusted hazard ratio estimates.

Overall, the researchers reported that 399 subjects (1.86% of the total) were found to have NAFLD over an 8-year period. Interestingly, use of HCQ was shown to be associated with a much lower risk of developing NAFLD, the team noted. This is especially true in women under 50 years old.

The team also noted other risk factors for the development of NAFLD, including higher prednisone doses, obesity and nonsteroidal anti-inflammatory drugs (NSAIDs). They also found that less traditional variables, such as patients with diabetes or higher cholesterol levels, were less common in this RA group.

Because the study relied on claims data, Chen advised caution and recommended regular liver function tests and increasing the frequency with which RA patients take potentially hepatotoxic drugs.2

“The mechanism by which HCQ reduces the risk of NAFLD may be its ability to increase adiponectin levels,” Chen said in a statement. “Estrogen has been reported to inhibit adiponectin production, and estrogen is inversely related to adiponectin levels. Therefore, the effect of HCQ in reducing the risk of NAFLD may be more pronounced in premenopausal women.”

Chen and colleagues do acknowledge that a major limitation of their study may be the inclusion of claims data, which does not protect against possible confounding bias.

“Only a double-blind randomized controlled trial can confirm the effectiveness of hydroxychloroquine in preventing or treating NAFLD,” Chen concluded in the statement.

Chen’s admission is another sign that patients will ultimately need FDA-approved treatments for NAFLD. At the same time, organizations such as the American Liver Foundation have launched projects such as “Think Liver Think Life” for patients to raise people’s awareness of the need for early screening for NAFLD.3

Some have speculated that the lack of treatment may be related to the association with alcohol, despite the existence of various liver diseases, and that this link may even affect NAFLD patients.

FDA approval of a drug in the near future may draw further attention to this disease and the patients who still face NAFLD.

The research explored here was funded by Taichung Veterans Hospital and Taichung Veterans General Hospital, Chiayi Branch.

  1. Chen H, CHEN D. Hydroxychloroquine is associated with reduced risk of non-alcoholic fatty liver disease in patients with rheumatoid arthritis: a population-based cohort study (Abstract). Arthritis Rheumatism. 2023;75(Supplement 9). https://acrabstracts.org/abstract/hydroxychloroquine-is-linked-with-a-decreased-risk-of-non-lingual-fatty-liver-disease-in-patients-with-rheumatoid-arthritis-a-population -Based on cohort study/. Accessed: November 10, 2023.
  2. Hydroxychloroquine may reduce the risk of non-alcoholic fatty liver disease in patients with rheumatoid arthritis, study finds. American College of Rheumatology. November 7, 2023. Accessed: November 10, 2023. https://rheumatology.org/press-releases/study-finds-hcq-lowers-risk-of-nonanol-fatty-liver-disease-in-ra-patient.
  3. Walter K. Hope is coming for people with often-neglected fatty liver disease. HCPLive. March 29, 2023. Accessed: November 10, 2023. https://www.hcplive.com/view/often-neglected-hope-fatty-liver-disease-patient.

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