Hepatokines and adipokines in NASH-related hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) is increasing in industrialized societies; this is likely secondary to the increasing burden of non-alcoholic fatty liver disease (NAFLD) and the metabolic syndrome. Cumulative studies suggest that NAFLD-related HCC may also develop in non-cirrhotic livers. However, the prognosis and survival of NAFLD-associated HCC does not differ from HCC with virus related etiologies. Thus, research has increasingly focused on NAFLD-related risk factors to better understand the biology of hepatocarcinogenesis and to develop new diagnostic, preventive, and therapeutic strategies. One important aspect thereof is the role of hepatokines and adipokines in NASH-related HCC, and their possible impact on novel screening and diagnostic approaches as well as potential therapeutic options. In this review, we compile current data supporting hepatokines and adipokines as potential markers for disease progression in NAFLD or as early markers for NAFLD-associated HCC. Increased serum concentrations of ANGPTL1, 2, and 8, FGF2, 19, and 21, apelin, chemerin, leptin, and visfatin have been found in NAFLD-associated HCC or were associated with poor prognosis. Reduction of ANGPTL4, hepassocin, and adiponectin serum concentrations were associated with HCC in NAFLD. While much work has to be done to elucidate mechanisms and interactions underlying alterations of hepatokines and adipokines in NAFLD-associated HCC, current data support possible utility of these factors for detection or even as therapeutic targets in NAFLD-associated HCC.