Non-Alcoholic Fatty Liver Disease, Liver Stiffness, and Subclinical Cardiorenal and Neurological Involvement in Patients with Rheumatoid Arthritis: A Multicenter Multidisciplinary Study

Abstract

Introduction/Objectives: Rheumatoid arthritis (RA) is a systemic chronic inflammatory autoimmune disease characterized by long-standing inflammation and extraarticular manifestations. Non-alcoholic fatty liver disease (NAFLD) is common in metabolic and inflammatory conditions, and it may be involved in increased prevalence of cardiovascular, renal and neurological abnormalities. The present work aimed to assess the associations between fatty liver grades, liver stiffness and subclinical involvement of the cardiorenal and neurological systems in RA patients, as well as evaluating the possible role of liver stiffness as an indicator of multiple system abnormalities.

Methods: total of 180 subjects were selected and divided equally into three groups: Group 1 (control group) without NAFLD or RA; Group 2 with NAFLD but without RA; and Group 3 with both RA and NAFLD.

Clinical and laboratory assessments were conducted, alongside evaluations of liver, cardiovascular, renal, and neurological status.

Hepatic steatosis and liver stiffness were assessed using ultrasound and transient elastography, utilizing the Controlled Attenuation Parameter (CAP) and Liver Stiffness Measurement (LSM). Cardio-renal and neurological assessments were conducted using estimated glomerular filtration rate (eGFR), left ventricular ejection fraction (LVEF), the Neurological Symptom Score (NSS), the Neurological Deficit Score (NDS), and the Modified Neurological Deficit Score (MSDS). Analyses included inter-group comparisons, correlation analysis, and multivariable regression models adjusted for age, sex, and body mass index.

Results : The three study groups showed an upward trend in mean liver stiffness, with values ranging from 4.58 ± 0.63 kPa in the control group to 8.16 ± 1.39 in patients with NAFLD without RA, and 11.15 ± 2.71 in patients with both NAFLD and RA. Correlation analyses revealed positive associations between liver stiffness measurement (LSM) and inflammatory markers, the urinary albumin-to-creatinine ratio, and neurological assessment scores, as well as negative associations with eGFR and LVEF; however, these correlations did not remain consistent in the adjusted regression analyses. The results demonstrated a positive association between liver stiffness (LSM) and the MSDS score (regression coefficient B = 0.309, 95% CI: 0.274–0.344; p < 0.001); however, adjusted associations of liver stiffness with estimated glomerular filtration rate (eGFR) (p = 0.829), left ventricular ejection fraction (LVEF) (p = 0.264), the Neurological Symptom Score (NSS) (p = 0.424), and the Neurological Deficit Score (NDS) (p = 0.060) were not statistically significant.

Both the non-alcoholic fatty liver disease (NAFLD) grade and the Controlled Attenuation Parameter (CAP) were positively associated with the MSDS score, yet neither showed a statistically significant adjusted association with eGFR or LVEF.

Conclusions: Preliminary results indicate increased liver stiffness in patients with overlapping NAFLD and rheumatoid arthritis (RA) and suggest a role for liver markers in certain outcome measures. Unadjusted analyses of other parameters revealed relationships with renal and cardiac function metrics; however, these relationships were not confirmed in the final models presented. Liver stiffness may warrant further attention as an indicator of extrahepatic pathologies, despite questions regarding its independent association and potential role as an intermediate variable.