Liver fat accumulation, or hepatic steatosis, is increasingly common and a frequent diagnosis in the medical field. Excess fat leads to liver fibrosis. There are two main types of fatty liver disease: alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Although similar in initial features, both involve similar progressive forms. Common mechanisms include alcoholic liver disease and NAFLD. This review explores similar downstream signaling events in AFLD and NAFLD, focusing on the gut microbiome. Downstream molecular events such as sirtuins, cytokeratins, and adipokines are considered. New therapeutic approaches are also presented. Keywords: Hepatic steatosis, Alcoholic liver disease, Nonalcoholic fatty liver disease, Microbiome, Adipokines, Cytokeratins, Sirtuins, Spleen, Patatin-like phospholipase domain-containing proteins, miRs The review discusses the nomenclature of fatty liver disease, including the new definitions of MAFLD and MASLD. It highlights the differences and similarities between AFLD and NAFLD, focusing on histopathological features. Both diseases share common molecular events, such as lipid metabolism alterations, redox imbalance, and adipokine involvement. The gut microbiome plays a key role in both diseases, with alterations in microbial composition contributing to liver damage. Sirtuins, particularly SIRT1, are important in regulating energy metabolism and inflammation. The spleen is also involved in lipid metabolism and immune function. Cytokeratins, such as K18, are associated with liver damage in both diseases. Sirtuins, including SIRT1 and SIRT4, are potential therapeutic targets. Genetic factors, such as PNPLA3 and TM6SF2, are also involved in the development of both diseases. miRNAs, such as miR-34a, miR-122, and miR-155, are implicated in the pathogenesis of NAFLD and ALD. The review also discusses the role of the gut microbiome in NAFLD, with alterations in microbial composition contributing to liver damage. The future directions include exploring the role of mTOR in NAFLD and the potential of n-3 PUFAs as a treatment for ALD. The review concludes that there are common molecular events between AFLD and NAFLD, and further research is needed to develop new therapeutic approaches.Liver fat accumulation, or hepatic steatosis, is increasingly common and a frequent diagnosis in the medical field. Excess fat leads to liver fibrosis. There are two main types of fatty liver disease: alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Although similar in initial features, both involve similar progressive forms. Common mechanisms include alcoholic liver disease and NAFLD. This review explores similar downstream signaling events in AFLD and NAFLD, focusing on the gut microbiome. Downstream molecular events such as sirtuins, cytokeratins, and adipokines are considered. New therapeutic approaches are also presented. Keywords: Hepatic steatosis, Alcoholic liver disease, Nonalcoholic fatty liver disease, Microbiome, Adipokines, Cytokeratins, Sirtuins, Spleen, Patatin-like phospholipase domain-containing proteins, miRs The review discusses the nomenclature of fatty liver disease, including the new definitions of MAFLD and MASLD. It highlights the differences and similarities between AFLD and NAFLD, focusing on histopathological features. Both diseases share common molecular events, such as lipid metabolism alterations, redox imbalance, and adipokine involvement. The gut microbiome plays a key role in both diseases, with alterations in microbial composition contributing to liver damage. Sirtuins, particularly SIRT1, are important in regulating energy metabolism and inflammation. The spleen is also involved in lipid metabolism and immune function. Cytokeratins, such as K18, are associated with liver damage in both diseases. Sirtuins, including SIRT1 and SIRT4, are potential therapeutic targets. Genetic factors, such as PNPLA3 and TM6SF2, are also involved in the development of both diseases. miRNAs, such as miR-34a, miR-122, and miR-155, are implicated in the pathogenesis of NAFLD and ALD. The review also discusses the role of the gut microbiome in NAFLD, with alterations in microbial composition contributing to liver damage. The future directions include exploring the role of mTOR in NAFLD and the potential of n-3 PUFAs as a treatment for ALD. The review concludes that there are common molecular events between AFLD and NAFLD, and further research is needed to develop new therapeutic approaches.