TY - JOUR
T1 - Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease
AU - van Son, Koen C.
AU - Verschuren, Lars
AU - Hanemaaijer, Roeland
AU - Reeves, Helen
AU - Takkenberg, R. Bart
AU - Drenth, Joost P. H.
AU - Tushuizen, Maarten E.
AU - Holleboom, Adriaan G.
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - 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.
AB - 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.
KW - hepatic stellate cells
KW - hepatocarcinogenesis
KW - hepatocellular carcinoma
KW - immune surveillance
KW - liver sinusoidal endothelial cells
KW - macrophages
KW - non-alcoholic fatty liver disease
KW - non-alcoholic steatohepatitis
KW - non-parenchymal cells
UR - http://www.scopus.com/inward/record.url?scp=85149115656&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/cancers15041308
DO - https://doi.org/10.3390/cancers15041308
M3 - Review article
C2 - 36831649
SN - 2072-6694
VL - 15
JO - Cancers
JF - Cancers
IS - 4
M1 - 1308
ER -