The Gut–Liver IgA Axis in Liver Disease: From Mucosal Immunity to Hepatic Inflammation and Cancer

Immunoglobulin A (IgA) connects mucosal defense with hepatic immune regulation, but its effects vary by anatomical compartment, antibody properties, and responding cell type. This narrative review synthesizes experimental and clinical evidence on the gut–liver IgA axis in alcohol-associated liver disease, metabolic dysfunction-associated steatotic liver disease and steatohepatitis, and hepatocellular carcinoma. We distinguish IgA-producing cells from secreted antibodies and IgA-responsive cells and examine antibody production, cellular trafficking, hepatic clearance, and biliary export. Experimental studies demonstrate the protective effects of mucosal IgA delivery and the context-dependent contributions of IgA-associated responses to inflammation, fibrosis, and impaired antitumor immunity. Human studies identify tissue and prognostic associations but do not establish a common intestinal source of pathogenic hepatic IgA. Collectively, these findings provide a rationale for investigating disease-specific, compartment-directed approaches targeting antibody production, cellular trafficking, protective export, or local effector responses. Clinical translation requires validation of causal mechanisms and intervention-specific biomarkers, as well as evidence of improved liver outcomes while preserving mucosal protection.