Detoxification State Fixation in Progressive Metabolic Liver Disease: A Conceptual Framework

Persistent hepatic de novo lipogenesis in progressive metabolic liver disease is not adequately explained by insulin resistance alone. We propose that sustained lipogenesis reflects fixation of an adaptive hepatic detoxification state that no longer resolves in an orderly manner. Chronic co-prioritization of lipogenesis and detoxification imposes redox burden, promotes oxidative stress, and supports inflammatory progression. This framework reframes disease persistence as failed state resolution and identifies restoration of reversibility as a testable therapeutic objective.