Seronegative autoimmune hepatitis in children : A real diagnostic challenge.

BACKGROUND AND AIM: Classical autoimmune hepatitis (AIH) is characterized by the presence of conventional autoantibodies (anti-smooth muscle, antinuclear and anti-liver-kidney-microsomal antibodies). The absence of such autoantibodies in some patients does not preclude AIH diagnosis or the need for its treatment. This group of patients was termed seronegative AIH. Whether non-conventional autoantibodies can identify this group of patients is still elusive. We aimed to study the prevalence of seronegativity of conventional autoantibodies and the occurrence of non-conventional autoantibodies in children with AIH. METHODS: In this study, 55 children with AIH were investigated for non-conventional autoantibodies (anti-neutrophil cytoplasmic antibodies, antibodies to soluble liver antigen, anti-tissue transglutaminase and antiplatelet antibodies). All the patients received immunosuppressive therapy and were assessed for treatment response. RESULTS: Of the patients 44 had classical AIH (type 1, 70.09%, type 2, 9.09%) and 20% were seronegative. The four studied non-conventional autoantibodies occurred in four patients, one for each. All non-conventional autoantibodies were exclusively associated with type 1 AIH. The clinical profile, ultrasonographic findings, liver biochemistry and histopathological findings were comparable in the classical and seronegative AIH. The majority of patients with classical (72.7%) and seronegative (54.5%) AIH were treatment responders. CONCLUSION: Seronegative AIH represents a substantial percentage of pediatric patients diagnosed with AIH. They were even negative for non-conventional autoantibodies. Furthermore, apart from autoantibodies, seronegative AIH is almost indistinguishable from the classical AIH and the majority of patients were treatment responders. This favorable response to immunosuppression deserves sustainable efforts for considering such a diagnosis and start therapy to halt disease progression is worthwhile.

Serological markers of autoimmunity in children with hepatitis A: relation to acute and fulminant presentation.

OBJECTIVES: Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH. METHODS: The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins. RESULTS: Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups. CONCLUSION: Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.