Table 5.

Associations between “Cancer Risk”, “Inflammation”, and “Metabolic Syndrome” in HCC.

Author(s) Publication Year Level of Evidence	Biomarkers Assessed	Conditions Assessed	Findings
Pocha et al., 2019 [72] level I	DAMP mTOR NF-kβ PAMOs ROS SCGA TLR TMA TNF-α VEGF	ALD BMI HBV HCV IR MetS NAFLD	In diabetic patients, heavy alcohol use of greater than 80 g/day increased the risk of HCC from 2.4 to 9.9. Obesity also had a synergistically effect.
Gutiérrez-Cuevas 2022 [73] level I		MetS Obesity Insulin resistance T2DM	NASH and HCC were closely associated with obesity and diabetes, including metabolic syndrome and NAFLD.
Montesi et al., 2013 [74] level I	ChREBP FFA G6PC GCKR GLP-1 LDL LPL MAP-K PI3-K	Hyperinsulinemia Insulin resistance NAFLD Obesity T2DM	Insulin resistance (reduced flux of PI3-K) was followed by compensatory hyperinsulinemia, as stimulus for carcinogenesis, along the MAP-K pathway and adaptive mechanisms chronically maintained in an obesiogenic environment favored oxidative stress and inflammation, improving the immune responses and increasing the carcinogenic potential.
Nakatsuka and Tateishi 2023 [75] level I	AKT HCV IGF-1 IL-6 NF-kβ PI3K mTOR ROS TNF-α	Chronic inflammation DNA damage Hepatocarcinogenesis, hyperinsulinemia IR Obesity Oxidative stress NAFLD Steatosis T2DM	More than 50% of cases of NAFLD-caused HCC, with a strong association with MetS and T2DM, may be due to its unique nature of increasing lipotoxicity-mediated chronic inflammation.
Phoolchund and Khakoo 2024 [76] level I	Genetic polymorphisms ROS	Inflammation MASDL MASH NAFLD Obesity	MASLD-HCC could develop at an earlier phase of fibrosis.

Abbreviations: ALD: alcohol-related liver disease; ChREBP: carbohydrate response element binding; DAMP: damage-associated molecular patterns; GCKR: glucokinase regulatory protein; G6PC: glucose 6-phosphatase; HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HCV: hepatitis C virus; IGF-1: insulin-like growth factor-1; IR: insulin resistance; MASDL: metabolic dysfunction-associated steatotic liver disease; MASH: metabolic dysfunction associated steatohepatitis; MetS: metabolic syndrome; NAFLD: non-alcoholic fatty liver disease; NASH: non-alcoholic steatohepatitis; PI3-K: phosphatidyl-inositol-3-kinase; ROS: reactive oxygen species; TMA: trimethylamine; T2DM: type 2 diabetes mellitus; TNF-α: tumor necrosis factor-α; TLR: toll-like receptor.