Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease: From Epidemiology to Diagnostic Approach.

Abstract

Simple SummaryNon-alcoholic fatty liver disease (NAFLD) is expected to become the leading cause of hepatocellular carcinoma (HCC) in the near future. In this article, we review the current knowledge about the epidemiology, risk factors, pathogenesis, clinical presentation and diagnostic approach to HCC in NAFLD. Knowledge of these facts is of great importance to improve the early identification of patients that are at risk, allowing for early detection of HCC and, thus, an improvement in clinical outcomes. This is especially important given that around 30% of NAFLD-related HCCs develop in a non-cirrhotic liver. The presence of diabetes, male sex, older age and Hispanic race, in addition to liver cirrhosis, are the most important risk factors for HCC in this setting. In summarising the current knowledge of genetic susceptibility, metabolic derangements and immunological mechanisms involved in the pathogenesis of NAFLD-related HCC, we illustrate the need for further research on this intriguing topic.Non-alcoholic fatty liver disease (NAFLD) is becoming the leading cause of liver morbidity worldwide and, as such, represents the pathogenic background for the increasing incidence of hepatocellular carcinoma (HCC). The annual incidence of NAFLD-related HCC is expected to increase by 45–130% by 2030. Diabetes mellitus is the most important risk factor for HCC development in NAFLD, with the risk further increased when associated with other metabolic traits, such as obesity, arterial hypertension and dyslipidemia. The highest risk of HCC exists in patients with advanced fibrosis or cirrhosis, although 20–50% of HCC cases arise in NAFLD patients with an absence of cirrhosis. This calls for further investigation of the pathogenic mechanisms that are involved in hepatocarcinogenesis, including genetics, metabolomics, the influence of the gut microbiota and immunological responses. Early identification of patients with or at risk of NAFLD is of utmost importance to improve outcomes. As NAFLD is highly prevalent in the community, the identification of cases should rely upon simple demographic and clinical characteristics. Once identified, these patients should then be evaluated for the presence of advanced fibrosis or cirrhosis and subsequently enter HCC surveillance programs if appropriate. A significant problem is the early recognition of non-cirrhotic NAFLD patients who will develop HCC, where new biomarkers and scores are potential solutions to tackle this issue.