When AL amyloidosis meets the liver: integrating clinical insight and current understanding

Light chain (AL) amyloidosis is a plasma cell-derived protein misfolding disorder in which structurally unstable monoclonal light chains aggregate into amyloid fibrils and deposit in target organs. Beyond simple disease burden, emerging evidence indicates that intrinsic light chain sequence and clonal properties actively shape organ tropism and clinical phenotypes. Hepatic involvement represents a distinctive but under-recognized manifestation, characterized by marked hepatomegaly and disproportionate alkaline phosphatase elevation, often preceding overt hepatocellular dysfunction. While usually occurring within multiorgan disease, hepatic-predominant presentations show enrichment of kappa-restricted clones, suggesting selective deposition driven by light chain biophysical features. Advances in plasma cell-directed therapies have transformed survival; however, delayed hepatic recovery despite rapid hematologic remission highlights dissociation between clonal suppression and amyloid clearance. Understanding how clonal biology governs organ-specific deposition and response kinetics may enable improved risk stratification and the development of mechanism-based strategies to accelerate organ recovery and optimize long-term outcomes.