The Emerging Factors and Treatment Options for NAFLD-Related Hepatocellular Carcinoma

SIMPLE SUMMARY: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease, and it is an increasing factor in the cause of hepatocellular carcinoma (HCC). The incidence of NAFLD has increased in recent decades, accompanied by an increase in the prevalence of other metabolic diseases, such as obesity and type 2 diabetes. However, current treatment options are limited. Both genetic factors and non-genetic factors impact the initiation and progression of NAFLD-related HCC. The early diagnosis of liver cancer predicts curative treatment and longer survival. Some key molecules play pivotal roles in the initiation and progression of NAFLD-related HCC, which can be targeted to impede HCC development. In this review, we summarize some key factors and important molecules in NAFLD-related HCC development, the latest progress in HCC diagnosis and treatment options, and some current clinical trials for NAFLD treatment. ABSTRACT: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, followed by cholangiocarcinoma (CCA). HCC is the third most common cause of cancer death worldwide, and its incidence is rising, associated with an increased prevalence of obesity and nonalcoholic fatty liver disease (NAFLD). However, current treatment options are limited. Genetic factors and epigenetic factors, influenced by age and environment, significantly impact the initiation and progression of NAFLD-related HCC. In addition, both transcriptional factors and post-transcriptional modification are critically important for the development of HCC in the fatty liver under inflammatory and fibrotic conditions. The early diagnosis of liver cancer predicts curative treatment and longer survival. However, clinical HCC cases are commonly found in a very late stage due to the asymptomatic nature of the early stage of NAFLD-related HCC. The development of diagnostic methods and novel biomarkers, as well as the combined evaluation algorithm and artificial intelligence, support the early and precise diagnosis of NAFLD-related HCC, and timely monitoring during its progression. Treatment options for HCC and NAFLD-related HCC include immunotherapy, CAR T cell therapy, peptide treatment, bariatric surgery, anti-fibrotic treatment, and so on. Overall, the incidence of NAFLD-related HCC is increasing, and a better understanding of the underlying mechanism implicated in the progression of NAFLD-related HCC is essential for improving treatment and prognosis.