Giant cell hepatitis associated with autoimmune hemolytic anemia: More evidence for B-cell depletion therapy for a rare immune mediated disease of infancy

Abstract

Giant cell hepatitis associated with autoimmune hemolytic anemia (GCH-AHA) is a rare but severe disease of infancy defined by an acute liver injury, histologically characterized by a widespread giant cell transformation and by an autoimmune hemolysis. GCH-AHA is thought to be immune-mediated being however a distinct entity from juvenile autoimmune hepatitis. In particular, GCH-AHA displays a less favorable response to conventional immunosuppressive treatment compared to classical juvenile autoimmune hepatitis, carrying a higher risk of mortality. In fact, since his first description, conventional therapy with prednisone with azathioprine has been used as first line treatment, however with frequent relapses during tapering, as well as severe side effects related to its prolonged use at high doses in early age. Due to the frequent occurrence of relapse, several immunosuppressive drugs have been tried as second line therapy with doubtful success. In case of severe liver dysfunction and/or severe anemia, transitory remission has been achieved with intravenous immunoglobulins administration, however with temporary response. B-cell depletion treatment, mostly with chimeric anti-CD20 monoclonal antibody (rituximab; RTX) has been used since 2004 with encouraging results mostly in refractory cases as second-line therapy. In this issue, the report of a series of 20 children with GCH-AHA from Shanghai, China, confirms the previous treatment experiences of a greater efficacy in obtaining complete remission of RTX or RTX treatment regimens compared to conventional regimens, with a good safety. To date, published experience with this rare disease suggests that RTX should be considered the cornerstone of treatment for complicated or relapsing cases of GCH-AHA and given the increasing evidence on its efficacy and safety, RTX might be even an acceptable option as first line therapy beside conventional treatment, to drastically reduce the cumulative steroids exposure and its side effects.