Fig. 1

Multiple metabolic dysfunctions contribute to the progression of non-alcoholic fatty liver disease (NAFLD). a NAFLD is defined as intrahepatic triglyceride content exceeding 5.5% within hepatocytes and has a sophisticated clinicopathological classification system [8]. Gradually, excessive lipid levels could overwhelm the capacity to deal with inflammation and hepatocyte ballooning due to lipotoxicity, which are characteristic of non-alcoholic steatohepatitis (NASH). Progressively, hepatic stellate cells are actively responsible for inflammation and hepatocyte death. This results in fibrosis through the generation of fibrogenic myofibroblasts [221], and 22% of patients develop cirrhosis [4]. Finally, patients with severe cirrhosis patients progress to hepatocellular carcinoma (HCC). b Available evidence indicates that multiple metabolic dysfunctions, such as obesity, type 2 diabetes mellitus (T2DM) and dysfunction of the gut microbiota, are the main risk factors for the progression of NAFLD [3]