Hepatocellular Carcinoma in Non-alcoholic Fatty Liver Disease:Current Progresses and Challenges

The rising global prevalence of metabolic diseases has increased the prevalence of non-alcoholic fatty liver disease(NAFLD),leading to an increase in cases of NAFLD-related hepatocellular carcinoma(HCC).To provide an updated literature review detailing epidemiology,risk factors,pathogenic pathways,and treatment strategies linked to NAFLD-related HCC,we conducted a literature search on PubMed from its inception to December 31,2021.About 25%of the global population suffers from NAFLD.The annual incidence of HCC among NAFLD patients is approximately 1.8 per 1,000 person-years.Older age,male sex,metabolic comorbidities,unhealthy lifestyle habits(such as smoking and alcohol consumption),physical inactivity,genetic susceptibility,liver fibrosis,and degree of cirrhosis in NAFLD patients are important risk factors for NAFLD-related HCC.Therefore,low-calorie diet,moderate-intensity exercise,treatment of metabolic comorbidities,and cessation of smoking and alcohol are the main measures to prevent NAFLD-related HCC.In addition,all patients with advanced NAFLD-related fibrosis or cirrhosis should be screened for HCC.Immune suppression disorders and changes in the liver microenvironment may be the main pathogenesis of NAFLD-related HCC.Hepatic resection,liver transplantation,ablation,transarterial chemoembolization,radiotherapy,targeted drugs,and immune checkpoint inhibitors are used to treat NAFLD-related HCC.Lenvatinib treatment may lead to better overall survival,while immune checkpoint inhibitors may lead to worse overall survival.Given the specific risk factors for NAFLD-related HCC,primary prevention is key.Moreover,the same treatment may differ substantially in efficacy against NAFLD-related HCC than against HCC of other etiologies.