Should Giant Cell Hepatitis With Autoimmune Haemolythic Anaemia Be Considered a Paediatric Autoimmune Liver Disease?

Abstract

Reply: We thank Dr Nastasio et al for their informative letter on giant cell hepatitis with Coombs positive haemolytic anaemia (GCH-AHA) (1). When we were commissioned by the ESPGHAN Hepatology Committee to write the Position Statement on Paediatric Autoimmune Liver Disease (2), we did consider the possibility of including GCH-AHA (3) and neonatal haemochromatosis (4), rare conditions with a possible autoimmune component to their pathogeneses. We decided not to include them for the following reasons. The major aim of the Position Statement was to formulate a diagnostic and management protocol for juvenile autoimmune liver disease on the basis of what available in the literature on conditions recapitulating classical autoimmune hepatitis, that is, sharing in common serological (positivity for anti-nuclear, anti-smooth muscle, anti-liver kidney microsomal type 1, anti-liver cytosol type 1, and/or anti soluble liver antigen) and histological (interface hepatitis, rosette formation, multilobular collapse) features. These conditions, which include autoimmune hepatitis, autoimmune sclerosing cholangitis (overlap between autoimmune hepatitis and sclerosing cholangitis) and autoimmune hepatitis after liver transplant, are not as rare as hitherto believed in the course of childhood, and, though sharing several laboratory and clinical features, differ in terms of diagnostic criteria, management, and outcome, prompting the need for a Position Statement. GCH-AHA, which most likely has an autoimmune component to its pathogenesis, is a rare disease affecting almost exclusively infants and is associated to a number of immune mediated disorders, as noted in Dr Nastasio's letter (5), raising the question as to whether the underlying problem in these children is immune dysregulation (6). The typical histological features of GCH-AHA are diffuse giant cell transformation of hepatocytes and inflammation, different from those of classical autoimmune hepatitis, rarely posing problems in regards to differential diagnosis between the 2 conditions. GCH-AHA does respond, at least partially, to immunosuppression and relapses frequently when treatment is withdrawn (5). B-cell–mediated immunity appears to be involved in both liver and systemic damage, as anti-B cell monoclonal antibodies (rituximab) are to date the most effective treatment for this condition (7), though not in all patients (8). In conclusion, we do agree that GCH-AHA has a strong immune/autoimmune component to its pathogenesis, but it differs from the more common and classical autoimmune liver diseases of childhood and adolescence. Multi-centre collaboration for a better characterisation of this serious disorder is warranted to understand its pathogenesis and devise more effective treatment.