Drug-induced liver injury (DILI) is a global health concern and one of the leading causes for the withdrawal of drugs from the market. DILI can exacerbate chronic liver injury to acute or chronic liver failure. The mitogen-activated protein kinase (MAPK) signaling cascade is the most conserved pathway that regulates key physiological processes, including cell proliferation, differentiation, inflammation, stress responses, and apoptosis. MAPK pathways such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 are activated by growth factors, cytokines and oxidative stress-related signaling. Increasing evidence indicates that drug metabolism-induced reactive oxygen species (ROS) can activate MAPK pathways such as ERK, JNK, and p38 MAPK in hepatocytes. Activation of MAPK through phosphorylation contributes to necrosis and apoptosis, mitochondrial toxicity, oxidative stress, inflammation, and impaired autophagy. MAPK activation can also stimulate nuclear factor-κB (NF-κB)-mediated inflammatory signaling, thereby amplifying liver injury. While the role of MAPK signaling in acetaminophen-induced hepatotoxicity is well established, emerging studies indicate that several classes of drugs can also trigger MAPK-mediated liver injury. In this context, the present review aimed to summarize the current understanding of MAPK signaling pathways involved in the pathogenesis of DILI, emphasis the roles of ERK, JNK, and p38 pathways in mediating oxidative stress, inflammation, and hepatocyte death. Understanding these mechanisms may help identify potential therapeutic targets and guide future clinical strategies for the prevention and management of DILI.

Hepatocellular carcinoma (HCC) is a common and lethal malignancy, with an increasing incidence globally, which is partially attributed to the rising prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). Complex metabolic rearrangements occur in MASLD-related HCC (MASLD-HCC) to promote the initiation and development of cancer. Nevertheless, comprehensive understanding of the metabolic transformations during the progression from MASLD to HCC remains limited. In this review, we introduce recent advances characterizing the metabolic changes in MASLD-HCC, thereby offering potential directions and clues for further studies.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with high morbidity and mortality worldwide. Its etiology is complex, involving multiple aspects such as viral infection, dietary exposure, chemical pollution, lifestyle and endogenous factors. This review conducted a comprehensive search in databases such as PubMed and Scopus using keywords including "hepatocellular carcinoma", "environmental factors", "epidemiological trends", and "prevention and treatment strategies". Relevant papers, including clinical case reports, reviews, and basic research, were included. This study systematically reviewed the mechanisms and epidemiological characteristics of external environmental factors such as viral infection, aflatoxin, arsenic, vinyl chloride, per- and polyfluoroalkyl substances, microplastics, oral contraceptives, nitrite, and microcystin-leucine arginine in the occurrence of HCC; internal environmental factors such as genetic susceptibility, diabetes, obesity, metabolic dysfunction-associated steatotic liver disease, metabolic syndrome, gut microbiota, and sex hormones; other factors such as alcohol consumption, smoking, insufficient sleep, lack of exercise and aging. A variety of preventive and intervention measures have been proposed, including hepatitis B vaccination, reduction of aflatoxin and alcohol exposure, tobacco control, antioxidant supplementation, regular rest and exercise. The prevention and control of HCC should range from infectious disease prevention and control to metabolic disease management and environmental governance, combined with individualized risk assessment and precise prevention strategies.