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

Table 2 Genetic risk factors for nonalcoholic fatty liver disease-associated hepatocellular carcinoma

Risk factors	Reported evidence	Ref.
PNPLA3	Carriage of rs738409 GG polymorphism is associated with 5.1–6.4-fold increased risk of HCC in NAFLD patients	[51-53,60]
	PNPLA3 G variant (GG vs CG vs CC) was not significantly associated with the risk of cardiovascular events extrahepatic cancers or overall death, but was associated with HCC (HR: 2.66) and liver-related death (HR: 2.42)
	Used for developing polygenic risk scores
TM6SF2	TM6SF2 minor allele carriage (rs58542926 C>T) was associated with advanced fibrosis/cirrhosis and HCC (OR, 2.8) in NAFLD patients	[54,55,60]
	Combined assessment with PNPLA3 and HSD17B13 variants were useful for risk stratification of NAFLD-HCC
	Used for developing polygenic risk scores
MBOAT7	MBOAT7 rs641738 C>T variants were associated with higher risk of HCC in NAFLD patients (OR, 1.65–2.10)	[56,60]
	Used for developing polygenic risk scores
TLR5	TLR5 rs5744174 TT genotype was a risk factor of HCC in patients with steatohepatitis-related cirrhosis (OR, 1.9)	[57]
STAT6	STAT6 rs167769 CC genotype was inversely associated with the risk of HCC in NASH patients (OR, 0.015)	[58]
YAP1	Carriage of YAP1 rs11225163 C allele was inversely associated with the risk of HCC in NASH patients (OR, 0.047)	[58]
HSD17B13	Combined assessment with PNPLA3 and TM6SF2 variants were useful for risk stratification of NAFLD-HCC	[55]
DYSF	DYSF rs17007417 T allele carriage was associated with increased risk of HCC in NAFLD patients (OR, 2.74)	[59]
GCKR	GCKR rs1260326 T allele carriage was associated with increased risk of HCC in NAFLD patients (OR, 1.38)	[59,60]
	Used for developing polygenic risk scores

PNPLA3: Patatin-like phospholipase domain 3; HCC: Hepatocellular carcinoma; NAFLD: Nonalcoholic fatty liver disease; HR: Hazard ratio; TM6SF2: Transmembrane 6 superfamily member 2; HSD17B13: 7-beta-Hydroxysteroid dehydrogenase 13; OR: Odds ratio; MBOAT7: Membrane-bound O-acyl-transferase domain-containing 7; TLR5: Toll-like receptor 5; STAT6: Signal transducer activator of transcription 6; NASH: Nonalcoholic steatohepatitis; YAP1: Yes-associated protein 1; DYSF: Dystrophy-associated fer-1-like protein; GCKR: Glucokinase regulator.