Study Calls for Greater Focus on Hepatic Health in Patients with RA, PsA

Miriam Ruiz Ponce

Credit: Miriam Ruiz Ponce on LinkedIn

Findings from a recent study are calling attention to the importance of monitoring hepatic health in patients with inflammatory arthritis, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA).¹

Results showed more than half of patients with inflammatory arthritis had steatosis despite having low disease activity, no obesity, and mostly normal biochemical, lipid, and metabolic parameters as well as levels of hepatic enzymes. Additionally, no significant differences in the presence of steatosis were observed based on methotrexate use and dosage.¹

“Liver damage is recognized as an extra-articular manifestation of psoriatic arthritis and rheumatoid arthritis, but the factors contributing to non-alcoholic fatty liver disease in the context of inflammatory arthritis have not been fully elucidated,” Miriam Ruiz Ponce, pre-doctoral researcher in biomedicine at the Maimonides Institute for Scientific Research of Cordoba in Spain, and colleagues wrote, describing the controversy around the potential hepatotoxic effects of methotrexate.¹

Liver damage is common in patients with RA and PsA, suspected to be driven at least partially by the use of potentially hepatotoxic drugs such as non-steroidal anti-inflammatory drugs and methotrexate. However, other factors contributing to the development of liver disease in these patients are not well understood.^2,3

To explore the factors contributing to NAFLD in patients with inflammatory arthritis, investigators conducted a cross-sectional study in a cohort of 108 patients without obesity. Of the total study population, 57 patients had RA and 51 had PsA.¹

Investigators assessed clinical and laboratory parameters, liver disease biomarkers, and several indexes to evaluate the probability of developing steatosis and/or hepatic fibrosis. These included the hepatic steatosis index; the fatty liver index; the triglyceride-glucose index; the fibrosis-4 score; and the aspartate-to-platelet ratio index. Investigators performed a transition hepatic elastography using FibroScan to assess the degree of hepatic stiffness or fibrosis, along with CAP to determine and quantify the percentage of fat infiltration in the liver.¹

Among the cohort, 57 participants were receiving methotrexate (n = 33 in the RA group, n = 25 in the PsA group) and were divided into 2 groups based on cumulative methotrexate doses: non-hepatotoxic risk group (<1.5g) and hepatotoxic risk group (>1.5g). Investigators retrospectively calculated the cumulative doses from the beginning of the treatment until the day of blood collection, calculating the total milligrams administered per week during the treatment period.¹

Investigators noted patients with RA had low disease activity (Disease Activity Score-28 [DAS28], 2.85 ± 1.35) and a disease duration of 4.63 ± 4.84 years, while patients with PsA also exhibited low disease activity (Disease Activity index in PSoriatic Arthritis [DAPSA], 11.38 ± 7.43) and a disease duration of 9.60 ± 6.63 years.¹

Among the entire cohort, FibroScan and CAP measurements revealed 51.9% of participants had steatosis and 7.5% showed hepatic fibrosis despite the absence of obesity. Based on ROC curve analysis, investigators noted the fatty liver index was the most accurate index for identifying a greater percentage of patients with steatosis (AUC, 0.733; P = .0003).¹

Among patients with PsA, 47.10% had steatosis and 11.80% had hepatic fibrosis. Patients with PsA and steatosis showed significantly elevated levels of CRP but had abnormal levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT).¹

Among patients with RA, 56.40% had steatosis and 3.60% had hepatic fibrosis. Patients with RA and steatosis showed significantly elevated levels of ACPAs, RF, and triglycerides, but investigators observed normal levels of AST, ALT, and ALP.¹

Of note, no significant differences were found in the profiles of inflammatory, metabolic, and liver disease biomarkers, FibroScan, and CAP values, or the prevalence of steatosis and fibrosis between the 2 hepatotoxic risk groups due to methotrexate use.¹

“These findings emphasize the need for comprehensive hepatic evaluation and follow-up in inflammatory arthritis patients with no obesity and low disease activity,” investigators concluded.¹ “High cumulative doses of methotrexate do not appear to influence the presence of steatosis compared to low cumulative doses.”

References

1. ^{Ruiz-Ponce M, Cuesta-López L, López Montilla MD, et al. CLINICAL ASPECTS OF HEPATIC STEATOSIS AND FIBROSIS IN NON-OBESE PATIENTS WITH RHEUMATOID ARTHRITIS AND PSORIATIC ARTHRITIS: EFFECTS OF CUMULATIVE DOSES OF METHOTREXATE. EULAR. doi:10.1136/annrheumdis-2024-eular.2891}
2. ^{Radovanović-Dinić B, Tešić-Rajković S, Zivkovic V, Grgov S. Clinical connection between rheumatoid arthritis and liver damage. Rheumatol Int. 2018;38(5):715-724. doi:10.1007/s00296-018-4021-5}
3. ^{Arthritis Foundation. How Can Psoriasis and Psoriatic Arthritis Affect Your Health? Accessed June 26, 2024. https://www.arthritis.org/diseases/more-about/psoriasis-and-psa-affect-your-health}