Commentary
Significant progress has been made over the past decade in our understanding of NASH pathogenesis, but gaps remain in our mechanistic knowledge of the precise metabolic triggers for disease worsening.
Many factors associated with dysregulated systemic metabolism have been implicated in some way with the progression from hepatic steatosis to NASH, including altered lipid metabolism, mitochondrial dysfunction, alterations in gut microbiome, oxidative stress, inflammatory cytokines, immune response, and others; however, it remains unclear which combination of these mechanisms are the key drivers of the disease.
This review by KK. Bence et al. focuses on early metabolic events in the establishment of NAFL and initial stages of NASH.
Similar to other metabolic diseases, the progression to more serious pathologic states is likely driven by several risk factors and manifests slightly differently in each individual depending on genetic risk, presence of other metabolic comorbidities (obesity and/or diabetes), lifestyle, diet, and environment.
As we learn more about the importance of interorgan communication in driving NASH pathogenesis, it is clear that this is a disease of altered systemic metabolism rather than a liver disease in isolation.