Individualized hepatocellular carcinoma risk: The challenges for designing successful chemoprevention strategies

Table 1 Risk factors for hepatocellular carcinoma

Viral	Environmental	Host related
HIV	Alcohol exposure	Age
HBV	Metabolic syndrome	Male sex
HCV		Genetics

HIV: Human immunodeficiency virus; HBV: Hepatitis B virus; HCV: Hepatitis C virus.

Table 2 Genetic associations with hepatocellular carcinoma at genome wide association studies level

Study	Patients	n	SNP locus	Strength	Comment
Kumar et al[85]	CHC	1730	MICA	OR 1.3	This study considers HCV-negative individuals as the controls, hence it isn’t useful in distinguishing HCC high risk population among HCV-related cirrhotic patients
	HCV neg	8376
	CHC-HCC	2115
Miki et al[86]	CHC	2390	DEPDC5	OR 2.2	Given the relatively small number of cases in the GWAS phase, the statistical power to detect an effect caused by this SNP was only 50%, compared to the 80% recommended to detect an association of the expected effect size
	CHC-HCC	922
Zhang et al[88]	CHB	1790	KIF1b	0.6	Confounding non-genetic HCC risk factors cannot be ruled out in multivariate analysis
	CHB-HCC	2317
Chan et al[89]	CHB	825	DLC1	1.3	Factors of selection bias cannot be excluded because 11.6% of the “genotyping cohort” had > 60 g alcohol consumption per day, secondly because 16.5% of the controls received antiviral treatment before enrolment
	CHB-HCC	595
Clifford et al[123]	HCC1	386	MHC II	p1 × 10-13	The viral infection status of controls was not ascertained with the consequence that there might be hypothetical cases with chronic liver disease
	Cirrhosis2	86
	Controls3	787

¹89% HBV or HCV viral infection;

²76% HBV or HCV viral infection;

³Not known viral status. CHC: Chronic hepatitis C; CHB: Chronic hepatitis B; GWAS: Genome-wide association study; HCC: Hepatocellular carcinoma; HCV: Hepatitis C virus; SNP: Single nucleotide polymorphism.