The Liver–Heart Axis in Rheumatoid Arthritis: Associations of Liver Fibrosis, Organokines, Endothelin-1, and Cardiovascular Risk

Liver involvement is frequent in rheumatoid arthritis (RA) and may progress from steatosis to fibrosis, cirrhosis, or hepatocellular carcinoma. Liver fibrosis (LF) in RA is multifactorial, but the available data are limited and the impact of methotrexate (MTX) remains controversial. In this cross-sectional study, 51 RA patients (46 females; mean age of 48.8 ± 8.2 years; and a median disease duration of 12 years) were enrolled. LF was assessed using non-invasive indices (the aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) and liver stiffness measurement (LSM) using shear wave elastography. Serum endothelin-1 (ET-1) and selected organokines (namely myostatin, resistin, and osteoprotegerin) were quantified by the ELISA. Associations of the APRI, FIB-4, and LSM with organokines and endothelin-1 were analyzed using univariable and multivariable linear regression, whereas correlations with the RA-specific cardiovascular (CV) risk score (ERS-RA) and echocardiographic parameters of left ventricular diastolic dysfunction (LVDD) were assessed using Spearman’s rank correlation. Myostatin and resistin showed a significant positive and significant negative association with LSM, respectively, while FIB-4 was negatively correlated with lateral and medial e’ velocities and positively with the ERS-RA. MTX use, mean weekly dose, cumulative dose, and endothelin-1 were not associated with the APRI, FIB-4, LSM, or LVDD. These exploratory findings support the potential role of myostatin and resistin in LF-related phenotypes and suggest that FIB-4 may capture aspects of both hepatic and cardiovascular risk in RA. RA patients with elevated FIB-4 values may require echocardiographic assessment and comprehensive CV risk evaluation. In this cohort, MTX exposure and endothelin-1 were not associated with LF or LVDD.