Autophagy is a conserved catabolic process that eliminates dysfunctional cytosolic biomolecules through vacuole-mediated sequestration and lysosomal degradation. Although the molecular mechanisms that regulate autophagy are not fully understood, recent work indicates that dysfunctional/impaired autophagic functions are associated with the development and progression of nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease (AFLD), and hepatocellular carcinoma (HCC). Autophagy prevents NAFLD and AFLD progression through enhanced lipid catabolism and decreasing hepatic steatosis, which is characterized by the accumulation of triglycerides and increased inflammation. However, as both diseases progress, autophagy can become impaired leading to exacerbation of both pathological conditions and progression into HCC. Due to the significance of impaired autophagy in these diseases, there is increased interest in studying pathways and targets involved in maintaining efficient autophagic functions as potential therapeutic targets. In this review, we summarize how impaired autophagy affects liver function and contributes to NAFLD, AFLD, and HCC progression. We will also explore how recent discoveries could provide novel therapeutic opportunities to effectively treat these diseases.

Cadmium (Cd) is a toxic pollutant that is associated with several severe human diseases. Cd can be easily absorbed in significant quantities from air contamination/industrial pollution, cigarette smoke, food, and water and primarily affects the liver, kidney, and lungs. Toxic effects of Cd include hepatotoxicity, nephrotoxicity, pulmonary toxicity, and the development of various human cancers. Cd is also involved in the development and progression of fatty liver diseases and hepatocellular carcinoma. Cd affects liver function via modulation of cell survival/proliferation, differentiation, and apoptosis. Moreover, Cd dysregulates hepatic autophagy, an endogenous catabolic process that detoxifies damaged cell organelles or dysfunctional cytosolic proteins through vacuole-mediated sequestration and lysosomal degradation. In this article, we review recent developments and findings regarding the role of Cd in the modulation of hepatotoxicity, autophagic function, and liver diseases at the molecular level.