**7. Heterogeneity of NASH/NAFLD from the viewpoints of etiopathogenic backgrounds and their sensitivity to each treatment procedure.**

NAFLD, the most common chronic liver disease in the United States, European and Asian countries is an extremely heterogeneous disorder in its etiopathogenic backgrounds and clinical manifestations [95]. The pathogenesis of NAFLD is multifactorial and complicated; thus, several systemic alterations and individual variations have been implicated and discussed [96].

The primary insult of lipid excess is followed by variable contributions from pathogenic drivers, such as lipotoxicity and immune system response with activation; and modifiers, such as genetic susceptibilities, high calory diet, added small amount of alcohol, and dysbiosis. Although there are considerable heterogeneities in NAFLD progression and the development of NASH, only a subset of NAFLD develops into NASH, which is the most unsolved problem and mysterious issue.

Potential explanations for this variability include differences in etiopathogenic drivers [2], dynamic multiphasic progression, constitutional/genetic backgrounds, complicated diseases, biological reactions, metabolic responses, etc. [97].
