Protracted, but not acute, hepatitis a virus infection is strongly associated with HLA-DRB1*1301, a marker for pediatric autoimmune hepatitis

HLA alleles are known to be associated with susceptibility to develop autoi mmune hepatitis (AH), and hepatitis A virus (HAV) infection is postulated a s a putative trigger for AH. We investigated whether HLA may influence the outcome of the HAV infection by studying 67 children with self-limited and 39 children with protracted forms of this infection. HLA typing of the unco mplicated forms showed no significant increase of any HLA class I or II all eles, In contrast, DRB1*1301 was present in 46.1% of the children with prot racted forms (vs. 9.8% in healthy controls; relative risk [RR]: 7.6; chi (2 ) 33.3; P = 2 x 10(-9)). In uncomplicated hepatitis, 45% developed anti-smo oth muscle antibody (SMA)/actin antibodies, but only 1 child had detectable antibodies after 3 months of infection onset. In contrast, after 1 year, 6 9% of the patients suffering protracted forms had titers of anti-SMA/actin antibodies that ranged between 1:40 and 1:160. Within their follow-up, 2 pa tients developed a Hashimoto's thyroiditis, but the remaining patients show ed no signs of developing autoimmune hepatitis. We conclude that the DRB1*1 301 haplotype is strongly associated with the protracted forms of HAV infec tion and suggest that the infection allows a sustained release of liver sel f-antigens, However, other still-unknown susceptibility genes are required for the full development of pediatric AH.