Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease?

Table 1 Results of a meta-analysis of hepatocellular carcinoma and metabolic syndrome, type 2 diabetes mellitus and obesity in 2012

Ref.	Database	Results
Esposito et al[13]	43 articles, including 38940 cases of cancer	Metabolic syndrome was associated with liver cancer (relative risk 1.43, P < 0.0001), especially in Asian populations
Chen et al[14] (2012)	26 prospective studies, including 25337 primary liver cancer cases	Overweight subjects have an increased risk of primary liver cancer of 1.48 (95%CI: 1.31-1.67), and obese subjects of 1.83 (95%CI: 1.59-2.11)
Tanaka et al[15] (2012)	9 cohort studies on Japanese populations	Overweight/obese individuals had a relative risk of 1.74 (95%CI: 1.33-2.28) for developing liver cancer
Wang et al[16] (2012)	17 case-control studies and 32 cohort studies	Statistically significant increased risk of HCC prevalence among diabetic individuals (RR = 2.31, 95%CI: 1.87-2.84). The pooled risk estimate of 17 case-control studies (OR = 2.40, 95%CI: 1.85-3.11) was slightly higher than that of 25 cohort studies (RR = 2.23, 95%CI: 1.68-2.96). Metformin treatment was potentially protective. Long duration of diabetes and sulfonylureas or insulin treatment possibly increased HCC risk. Increased risk of HCC mortality (RR = 2.43, 95%CI: 1.66-3.55) for individuals with (vs without) diabetes
Wang et al[17] (2012)	25 cohort studies	Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs = 2.01, 95%CI: 1.61-2.51), compared with individuals without DM
		There was a statistically significant heterogeneity among these studies (Q = 136.68, P < 0.001, I(2) = 87.6%). Analyses sub-grouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR = 1.56; 95%CI: 1.30-1.87)

Table 2 Principal risk factors for developing hepatocellular carcinoma, epidemiological evidence

Risk factors for HCC	Incidence of HCC	Epidemiology
NAFLD	1%-2% overall[19]	The prevalence of NAFLD in the general population of Western countries is 20%-30%[20]
NASH	4%-27% overall[21]	About 2%-3% of the general population is estimated to have NASH[20]
HBV	3%-8% overall[22]	Two billion people worldwide have been exposed to HBV, and 400 million people have chronic HBV infection[24]
	0%-5% per year[23]
HCV	1%-7% overall[25]	About 150 million people worldwide are infected with HCV[28]
	2%-8% per year[26,27]
Alcohol	1%-2% per year in cirrhotics[29]	The WHO reports about two billion alcohol consumers worldwide and 76.3 million people with diagnosable alcohol use disorders[30]

HCC: Hepatocellular carcinoma; NAFLD: Non-alcoholic fatty liver disease; HCV: Hepatitis C virus; HBV: Hepatitis B virus; WHO: World Health Organization.