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

Abstract

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.

Effect of COVID-19 Pandemic on Hepatocellular Carcinoma Diagnosis: Results from a Tertiary Care Center in North-West Italy

“…In our study, the prevalence of cirrhotic patients was slightly higher than that expected from the literature data (about 80% [23]), but compatible with a cohort in which HCV is still the main cause [24], despite a progressive increase in NAFLD as a cause (or a contributing cause) of HCC (from 17% to about 40%). This figure reflects the prediction that NAFLD will be the leading cause of HCC over the next decade [25], but it appears to have even worsened perhaps due to social restrictions and home confinement that limited physical activity; furthermore, we may have been more sensitive to reporting NAFLD as a contributing cause: in fact, its increase is not proportional to the decrease in viral infection, but is added to them. Our work presents some limitations, mainly that it is a retrospective, with limited sample size, and single-center study, which limits the applicability of our results: a validation of our results in a multicenter setting is mandatory.…”

Fine-tuning of regulatory T cells is indispensable for the metabolic steatosis-related hepatocellular carcinoma: A review

“…Chronic hepatic diseases, such as ALD and NAFLD, are emerging as the foremost cause of liver cancer and morbidity worldwide. It has been estimated that the prevalence of NAFLD-associated HCC will drastically increase (up to 45%-130%) in a decade (Grgurevic et al, 2021). The progression of hepatic diseases largely depends on several factors, such as ROS, oxidative stress, lipotoxicity, IR and gut microbiota.…”

Risk factors and diagnostic biomarkers for nonalcoholic fatty liver disease-associated hepatocellular carcinoma: Current evidence and future perspectives

“…Several studies have demonstrated that (mostly type 2) diabetes mellitus is associated with an increased risk of HCC development in NAFLD patients. The hazard ratio for HCC in diabetic patients has been reported to be around 2.2–4.2[ 22 , 26 , 27 ] (Table 1 ). In a nationwide Japanese study, the annual incidence of HCC was only 0.11% in diabetes patients overall.…”