Hepatic Control of Immunometabolism in ARDs
A Nature Reviews Rheumatology review argues that the liver is an upstream player in autoimmune rheumatic disease and not only a bystander. Hepatocytes make β2-glycoprotein I, paraoxonase-1 (PON1), complement, CRP, hepcidin and most circulating antioxidants, and they process nutrients, drugs, toxins and gut microbial products. In lupus-prone mice, hepatic mitochondrial oxidative stress and mTOR activation come before autoantibodies, and loss of PON1 may let β2GPI become an immunogenic antigen in lupus and antiphospholipid syndrome. The review also covers lupus hepatitis versus autoimmune hepatitis, MASLD in rheumatic disease, how disease-modifying drugs affect the liver, when to biopsy, and liver-directed treatments, most of which are still experimental.