Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis

OBJECTIVE: Antibodies to soluble liver antigen/liver-pancreas are highly specific markers of type 1 autoimmune hepatitis that have been associated with relapse. Our aim was to determine if these antibodies are reflective of a genetic predisposition for recrudescent disease. METHODS: One hundred forty-four white North American patients were evaluated by an enzyme immunoassay and by Western blot using recombinant soluble liver antigen/liver-pancreas; 122 were assessed for class II human leukocyte antigens (HLAs). RESULTS: Twenty-two patients (15%) had antibodies to soluble liver antigen/liver-pancreas. These patients were indistinguishable from seronegative patients by clinical, laboratory, and histological features at presentation. Patients with antibodies to soluble liver antigen/liver pancreas had HLA DR3 (79% vs 50%, p = 0.02) more commonly and HLA DR4 less often (16% vs 47%, p = 0.02) than patients with smooth muscle antibodies and/or antinuclear antibodies. Seropositivity was associated with DRB1*0301 and seronegativity was associated with DRB1*0401. Relapse after drug withdrawal occurred in all patients with antibodies to soluble liver antigen/liver-pancreas and at a higher frequency than in patients with conventional antibodies (100% vs 78%, p = 0.05). CONCLUSIONS: Antibodies to soluble liver antigen/liver pancreas are associated with HLA DR3 and the susceptibility allele, DRB1*0301. Antibodies to soluble liver antigen/liver-pancreas may be surrogate markers of a genetic propensity for recrudescent disease or the target autoantigen. They may be complementary to antinuclear antibodies and smooth muscle antibodies in diagnosis and management.