Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain.
Rheumatology service/Department of Medical and Surgical Sciences, Maimonides Institute for Research in Biomedicine of Cordoba (IMIBIC)/ /University of Cordoba/ Reina Sofia University Hospital, Córdoba, Spain.
Eur J Intern Med. 2023 Dec;118:49-58. doi: 10.1016/j.ejim.2023.08.002. Epub 2023 Aug 4.
The aim of this study was to explore the impact of arthritis on liver function using different approaches in vivo and in vitro.
A cross-sectional study was performed on 330 non-obese/non-T2DM subjects: 180 RA patients, 50 NAFLD non-RA patients, and 100 healthy donors (HDs). A longitudinal study was conducted on 50 RA patients treated with methotrexate for six months. Clinical and laboratory parameters and markers of liver disease were collected. Mechanistic studies were carried out in both the CIA mouse model and hepatocytes treated with anti-citrullinated protein antibodies (ACPAs).
RA patients have an increased risk of suffering from liver disease independent of obesity or T2DM. This risk was associated with factors such as insulin resistance, autoantibodies, inflammation, and component C3. Methotrexate treatment for six months was associated with liver abnormalities in those newly-diagnosed patients having CV risk factors. ACPAs induced a defective hepatocyte function, promoting IR and inflammation. The induction of arthritis in mice caused the infiltration of immune cells in the liver and increased inflammatory, apoptotic, and fibrotic processes.
RA patients may experience mild to moderate liver inflammation due to the infiltration of T, B cells, and macrophages, and the action of ACPAs. This is independent of obesity or diabetes and linked to systemic inflammation, and disease activity levels. The negative effects of methotrexate on liver function could be restricted to the concomitant presence of cardiovascular risk factors.
本研究旨在通过体内和体外不同方法探讨关节炎对肝功能的影响。
对 330 例非肥胖/非 T2DM 受试者进行横断面研究：180 例 RA 患者、50 例非 RA 的 NAFLD 患者和 100 例健康供体（HDs）。对 50 例接受甲氨蝶呤治疗 6 个月的 RA 患者进行纵向研究。收集临床和实验室参数以及肝病标志物。在 CIA 小鼠模型和用抗瓜氨酸化蛋白抗体（ACPAs）处理的肝细胞中进行了机制研究。
RA 患者患肝病的风险增加，与肥胖或 T2DM 无关。这种风险与胰岛素抵抗、自身抗体、炎症和补体 C3 等因素有关。新诊断的伴有心血管危险因素的患者接受甲氨蝶呤治疗 6 个月后，出现肝异常。ACPAs 诱导肝细胞功能缺陷，促进 IR 和炎症。在小鼠中诱导关节炎导致免疫细胞浸润肝脏，并增加炎症、凋亡和纤维化过程。
RA 患者可能会出现轻度至中度肝脏炎症，原因是 T、B 细胞和巨噬细胞的浸润以及 ACPAs 的作用。这与肥胖或糖尿病无关，与全身炎症和疾病活动水平有关。甲氨蝶呤对肝功能的负面影响可能仅限于同时存在心血管危险因素。
