Interaction of IFNL3 with insulin resistance, steatosis and lipid metabolism in chronic hepatitis C virus infection

Table 1 Summary of the IFNL3 polymorphisms identified by genome-wide association studies

GWAS	Total population	IFNL3 SNP	Wild (responder) type/non-responder allele
Suppiah et al[3]	848	rs80999172	T/G
Tanaka et al[4]	314	rs8099917	T/G
		rs12980275	A/G
Rauch et al[5]	914	rs8099917	T/G
Ge et al[8]	1137	rs129798601	C/T

¹rs12979860 and

²rs8099917 single nucleotide polymorphisms (SNPs) are strongly associated with clearance and commonly used in clinical practice. GWAS: Genome-wide association studies.

Table 2 IFNL3 polymorphisms and steatosis in chronic hepatitis C

No. of patients	Study design	HCV genotype	IFNL3 SNP	Results	Ethnicity	Ref.
1604	Retrospective	HCV-1	rs12979860	CC genotype associated with higher pretreatment LDL-C levels and less frequent hepatic steatosis	Caucasians	46
145180	Retrospective analysis of two Independent cohorts: (1) (antifibrotic) Study cohort; (2) Duke cohort	HCV-1	rs12979860	CC genotype associated with less hepatic steatosis	122 (84.1%) Caucasians130 (72.2%) Caucasians	47
434	multi-center, Retrospective	HCV-1	rs12979860	CC genotype associated with less frequent hepatic steatosis	Caucasians	48
202	Prospective	HCV-1: 181 (89.6%)	rs12979860	CC genotype associated with less frequent hepatic steatosis	Caucasians	49
		HCV-4: 21 (10.4%)
153	Retrospective	HCV-1b	rs8099917	TT genotype associated with less hepatic steatosis (vesicular and clear cell changes)	Japanese	50
626	Retrospective analysis of the Swiss Hepatitis C Cohort Study	Non-HCV-3	rs12980275	G associated with less hepatic steatosis only in non-HCV-3	Caucasians	51
122	Retrospective	HCV-1b	rs8099917	No association with hepatic steatosis	Japanese Mongolian	52
445	Retrospective	HCV-1: 303 (68.1%)	rs12979860	No association with hepatic steatosis	Caucasian	53
		HCV-2: 13 (2.9%)
		HCV-3: 82 (18.4%)
		HCV-4: 47 (10.6%)

HCV: Hepatitis C virus; LDL-C: Low-density lipoprotein cholesterol.

Table 3 IFNL3 polymorphisms and insulin resistance in chronic hepatitis C

Cohorts size	Study design	HCV genotype	IFNL3 SNP	% IR	HOMA-IR	Results	Ethnicity	Ref.
434	Multi-center, retrospective	HCV-1 (n = 434)	rs12979860	50%	> 3	CC genotype associated with reduced IR	Caucasians	48
202	Prospective	HCV-1 (n = 181)	rs12979860	32.20% (65/202)	≥ 3	CC genotype associated with reduced IR	Caucasians	49
		HCV-4 (n = 21)
328	Retrospective	HCV-1 (n = 328)	rs8099917	50% (84/168) in TT genotype vs 69.7% (53/76) in TG/GG genotype	≥ 2.45 in TT genotype vs≥ 1.55 in TG/GG genotype	No differences in IFNL3 genotype distribution according to HOMA-IR	Japanese	57
240	Retrospective	HCV-1 (n = 188)	rs12979860	46% (89/193)	≥ 2	No differences in HOMA-IR levels according to IFNL3 genotypes	Caucasians	59
		HCV-2 (n = 3)
		HCV- (n = 30)
		HCV-4 (n = 19)

HCV: Hepatitis C virus; IR: Insulin resistance.