FIGURE 4.

Metabolite pathway alterations involved in chronic DILI with fibrosis. A typical feature was that the synthesis of primary bile acids and histidine metabolites, and a series of metabolites related to lipids (e.g., ether lipid and sphingolipid) were significantly increased. This accumulation of lipid metabolisms persisted from the development of nonsignificant fibrosis to significant fibrosis to advanced fibrosis. In advanced fibrosis, metabolites of the fatty acid and pentose phosphate pathways were accumulated while the glycerophospholipid metabolites were found to decrease.