Search

Simple Summary: The incidence of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Compared to HCC caused by other chronic liver diseases, NAFLD-related HCC is often detected later, because it more commonly arises before cirrhosis has occurred. Because of this late diagnosis, NAFLD-related HCC is often more advanced at time of diagnosis, resulting in fewer curative treatment options. Most research in the pathogenesis of HCC has focused on the disease processes in hepatocytes, the most abundant type of liver cells. However, other cell types, such as cells of the immune system and cells that regulate connective tissue formation, also play an important role in the development of NAFLD-related HCC, both by contributing to the development of HCC itself and by interfering with the immune system's ability to attack cancer cells. In this paper, we review the role of different cell types in the development of NAFLD-related HCC. Hepatocellular carcinoma (HCC) in the setting of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis and even in the pre-cirrhotic state is increasing in incidence. NAFLD-related HCC has a poor clinical outcome as it is often advanced at diagnosis due to late diagnosis and systemic treatment response is poor due to reduced immune surveillance. Much of the focus of molecular research has been on the pathological changes in hepatocytes; however, immune cells, hepatic stellate cells, liver sinusoidal endothelial cells and the extracellular matrix may play important roles in the pathogenesis of NAFLD-related HCC as well. Here, we review the role of non-parenchymal cells in the liver in the pathogenesis of HCC in the context of NAFLD-NASH, with a particular focus on the innate and the adaptive immune system, fibrogenesis and angiogenesis. We review the key roles of macrophages, hepatic stellate cells (HSCs), T cells, natural killer (NK) cells, NKT cells and liver sinusoidal endothelial cells (LSECs) and the role of the extracellular matrix in hepatocarcinogenesis within the steatotic milieu. [ABSTRACT FROM AUTHOR]

Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains. [ABSTRACT FROM AUTHOR]