Antibodies to Liver-Specific Lipoprotein in Children with Chronic Liver Disease Due to “Autoimmune” Chronic Active Hepatitis, Cystic Fibrosis, and α1-Antitrypsin Deficiency

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Abstract
Antibodies to a liver-specific lipoprotein complex (LSP) were determined by radioimmunoassay in the sera of 65 children with possible chronic liver disease. Thirteen had “autoimmune” chronic active hepatitis (CAH), 21 α1-antitrypsin deficiency PiZ (α1-ATD), all having significant liver disease, while 10 of 31 children with cystic fibrosis (CF) had abnormal biochemical tests of liver function, six having cirrhosis. Sera from 12 (92%) of 13 untreated CAH patients contained detectable anti-LSP antibodies, the highest titres occurring in those with anti-liver/kidney microsomal or smooth muscle antibodies. Titre of anti-LSP antibodies correlated with piecemeal necrosis of periportal hepatocytes in liver biopsies, but not with standard biochemical tests of liver function or serum immunoglobulin concentrations. The incidence of LSP antibodies fell as liver damage improved with immunosuppressant therapy, being positive in 18 of 26 sera from children in whom the transaminases were still above normal, but positive in only two of 20 in whom transaminase values were within the normal range (2 = 16, p<0.001). Sera from two of 31 patients (6%) with CF contained anti-LSP antibodies as did sera from six of 21 patients with α1-ATD. Antibody concentrations were lower than in CAH, and in α1-ATD the presence of anti-LSP could not be correlated with the presence or absence of piecemeal necrosis on liver biopsy. Our data suggest that autoimmune mechanisms involving antibody to hepatocyte membrane components have a role in the pathogenesis of chronic liver disease in autoimmune CAH in children as in adults. Autoimmune mechanisms involving antibodies to LSP may perpetuate or potentiate liver damage in some patients with α1-ATD, but the precise pathogenic role and factors controlling it remain to be defined.