Influence of genes, sex, age and environment on the onset of autoimmune hepatitis

Table 1 Clinical and biochemical characteristics of type 1 and type 2 autoimmune hepatitis

	Characteristics
Type 1 AIH	Anti-SMA, anti-ANA and/or anti-SLA
	Mean age of onset: 10 yr old
	Female:Male ratio 3:1
	Higher incidence
	Frequently associated with IBD and sclerosing cholangitis
Type 2 AIH	Anti-LKM1 and/or anti-LC1
	Mean age of onset: 6.5 yr old
	Female:Male ratio 9:1
	Associated with HLA DR3, DR7 and DQB1*0201
	More severe disease
	More likely to be resistant to treatment

Table 2 Specific susceptibility genes in type 1 and type 2 autoimmune hepatitis

Genes	Population	Type of AIH	Linkage disequilibrium	References
MHC genes
HLA-A1-B8	North-America, Europe	1	Yes	[1415]
HLA-DRB1*0301	North-America, UK, Spain, Argentina	1 and 2	Yes	[141525]
HLA-DRB1*0401	North-America, Europe		ND	[1415]
HLA-DRB1*0404	Mexico	1	ND	[18]
HLA-DRB1*0405	Argentina, Japan	1	-	[1920]
HLA-DRB1*1301	North-America, Europe, Brazil, Argentina	1	Yes	[1621]
HLA-DRB1-07	Germany, Brazil, UK	2	Yes	[2324]
HLA-DRB3*01	Brazil			[2223]
HLA-DQB1*0201	North-America, Europe	2	Yes	[16]
HLA-DQB1*0603	North-America, Europe	2	Yes	[16]
Non-MHC genes
IgA	Europe	1		[2829]
C4A	Europe, North-America	1 and 2	Yes	[3031]
CTLA4	North-America, Europe	1	Yes	[3536]
Fas	Japan, North-America	1	ND	[3738]
Vitamin D receptor	Germany	1 and 2	ND	[39]
TNFa*2	North-America, UK	1	Yes	[4344]

ND: Non-determined.

Table 3 Putative candidate viruses as triggering event in autoimmune hepatitis

Putative virus as AIH trigger event	Evidences	References
Hepatitis A virus	Case reports	[94–96]
Hepatitis B virus	Case reports	[9798]
Hepatitis C virus	Specific AIH autoantibodies	[87–89]
	Cross-Reactivity at T and B-cell level	[90–92]
Epstein-Barr virus	Case reports	[66–69]
Human herpes virus 6	Sequence similarities	[99]
Herpes simplex virus	Sequence similarities	[102]
	Cross-reactivity at B-cell level	[102]