Exposure to environmental pollutants is intimately linked to the onset and progression of chronic liver disease; however, its quantitative contribution to disease burden remains inadequately defined. Although most existing studies concentrate on individual toxicants or discrete signaling pathways, they often fail to elucidate the dynamic transition from early adaptive responses to chronic pathological transformation. Synthesizing current evidence, this review integrates multilevel mechanisms to construct a conceptual framework for continuous pathological progression. We define environmental hepatotoxicity as a dynamic continuum encompassing sequential stages, from adaptive imbalance to chronic pathological advancement. Within this framework, distinct environmental exposures exert dominant effects at specific stages, dictated by their unique molecular response profiles. Individual heterogeneity modulates the trajectory of chronic progression by altering stress tolerance thresholds and systemic homeostatic remodeling. Building on this model, we propose a stage-oriented intervention paradigm that shifts strategically from augmenting adaptive capacity to arresting injury amplification and ultimately reconstructing systemic homeostasis. This framework provides a theoretical scaffold for integrating exposomics with mechanistic research; nevertheless, clinical translation hinges on quantifying low-dose exposure thresholds, identifying dominant factors in combined exposures, and developing stage-specific biomarkers.
Wen et al. (Fri,) studied this question.