Abstract: Objective To summarize the research progress in the adaptive response of hepatocytes against intrinsic drug-induced liver injury so as to provide a safe medication regimen for drugs with potential hepatotoxicity. Methods By searching databases for related literature published as of January 10, 2025, the mechanism by which adaptive response of hepatocytes helped alleviate intrinsic drug-induced liver injury was studied in terms of drug metabolism, mitochondrial stress response and hepatocyte proliferation. Results Drug-induced liver injury coincided with the activation of adaptive response that was believed to maintain liver homeostasis and mitigate intrinsic drug-induced liver injury by increasing detoxification metabolism, reducing toxic metabolism, promoting mitophagia, enhancing the antioxidant system, promoting hepatocyte proliferation, and regulating functional gene expressions in surviving hepatocytes. Conclusion The mechanism of adaptive response is complex and plays an important role in endogenous protection against intrinsic drug-induced liver injury. The study of adaptive response can provide a clinically safe and rational regimen for potentially hepatotoxic drugs and facilitate the treatment and prevention of intrinsic drug-induced liver injury.

Key words: Intrinsic Drug-Induced Liver Injury, Adaptive Response, Drug Metabolizing Enzymes, Mitochondrial Stress Response, Liver Regeneration