Regulatory mechanism of HIF-1α and its role in liver diseases: a narrative review

Objective: To summarize the structure, regulatory mechanism, and target genes of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and to comprehensively expound its role in various chronic liver diseases, thus providing a new perspective on the treatment of various liver diseases. Background: Liver disease, especially chronic liver disease, is a long-standing public health problem; the mortality rate due to end-stage cirrhosis and liver cancer is high worldwide and continues to grow. Moreover, there is a lack of effective targeted therapy for most liver diseases, such as fatty liver, alcoholic liver disease (ALD), and advanced liver cancer, for which drug treatment approaches are extremely limited. As the liver is a highly aerobic organ, an insufficient oxygen supply can induce a series of diseases, and HIF proteins play an important role in these processes. Methods: Literature on HIF-1 alpha and its effects on various liver diseases were extensively searched, and the feasibility and challenges of targeting HIF-1 alpha to treat various chronic liver diseases were analyzed. Conclusions: HIF-1 alpha is widely involved in the occurrence, development, and prognosis of ALD, nonalcoholic fatty liver disease (NAFLD), acetaminophen (APAP)-induced liver injury (AILI), viral hepatitis, hepatocellular carcinoma ( HCC), and other liver diseases. HIF-1 alpha participates in complex signaling pathways, and its expression is regulated in many liver diseases. These results suggest the feasibility and clinical significance of targeting HIF-1 alpha to treat liver diseases.