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

Table 1 Clinical risk factors for nonalcoholic fatty liver disease-associated hepatocellular carcinoma

Risk factors	Reported evidence	Ref.
Liver fibrosis	The annual incidence rate of HCC in NAFLD patients with cirrhosis was more than 10 times higher than in those without	[15,22,24,25]
	Non-invasive fibrosis markers (e.g., FIB-4 index, M2BPGi, and shear wave velocity in VTQ) also had significant associations with the risk of NAFLD-HCC
Diabetes	Associated with increased risk of HCC in NAFLD patients (hazard ratio: 2.2–4.2)	[22,26,27]
Hypertension	May be an independent risk factor for NAFLD-HCC	[29]
Dyslipidemia	May be an independent risk factor for NAFLD-HCC	[29]
Age	Increased age was an independent risk factor for HCC in patients with NASH-related cirrhosis	[15,34]
	NAFLD patients aged ≥ 65 had 1.83 times higher risk of HCC than those aged < 65
Male sex	Male patients with NASH-related cirrhosis had 4.34 times higher risk of HCC than female patients	[34]
Ethnicity	Hispanic ethnicity was associated with 1.59 times higher risk of HCC in NAFLD patients compared to white ethnicity (however, there have been conflicting results)	[15]
Mild alcohol intake	Associated with increased risk of HCC in NAFLD patients (hazard ratio: 3.6–4.8)	[38,39]
Elevated liver enzymes	Associated with increased risk of HCC in NAFLD patients (hazard ratio: 2.1–8.2)	[41-43]

HCC: Hepatocellular carcinoma; NAFLD: Nonalcoholic fatty liver disease; FIB-4: Fibrosis-4; M2BPGi: Mac-2-binding protein glycosylation isomer; VTQ: Virtual touch quantification; NASH: Nonalcoholic steatohepatitis.