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HIF-1 activates glycolysis-related genes, including pyruvate dehydrogenase kinase 1 (PDK1), increasing the conversion of glucose to pyruvate and subsequently to lactate by inactivating PDH, which is considered critical for metabolic adaptation to hypoxia [74] [Figure 1F]

56 It has also been reported that in fulminant hepatic failure, toxic substances released from the necrotic hepatic remnant and lack of detoxification of substances from the gut inhibit or delay liver regeneration and the recovery of hepatic function including aminotransferase production

prolonged overactivation may promote oncogenic pathways or, as seen in clinical trials with bardoxolone methyl, adverse renal outcomes (Pergola et al., 2021)

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