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.