Giant Cell Hepatitis and Autoimmune Hemolytic Anemia Successfully Treated With Rituximab

Miloh, Tamir; Manwani, Deepa; Morotti, Raffaella; Emre, Sukru; Shneider, Benjamin L.; Kerkar, Nanda

doi:10.1097/mpg.0b013e31802e9739

Cited by 28 publications

(47 citation statements)

References 13 publications

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“…13 Its use in treating GCH-AHA has been empirically tried in 5 children. 2,3,5,6 In 2 of these patients, the effect of rituximab was shown to be temporary. 2,5 Except for patient 1, all patients presented here showed several relapses of both anemia and the liver condition over the years after the first series of injections.…”

Section: Discussionmentioning

confidence: 99%

“…[2][3][4][5][6] Empirical use of rituximab has been reported to treat GCH-AHA, with diverse results. 2,3,5,6 Coombs-positive AHA is well known to result from the activation of complement cascade on the red cell surface secondary to immunoglobulin G (IgG) binding. 7 We recently showed that hepatocyte injury in GCH-AHA is complement mediated and that the portal inflammatory infiltrate is constituted mainly of macrophages and neutrophils, both suggesting B cell-mediated autoimmunity as the predominant mechanism of disease.…”

mentioning

confidence: 99%

“…2 Treatment strategies include steroids, azathioprine, mycophenolate mofetil (MMF), calcineurin inhibitors, sirolimus, intravenous immunoglobulin (IVIg), cyclophosphamide, and splenectomy. [2][3][4][5][6] Empirical use of rituximab has been reported to treat GCH-AHA, with diverse results. 2,3,5,6 Coombs-positive AHA is well known to result from the activation of complement cascade on the red cell surface secondary to immunoglobulin G (IgG) binding.…”

mentioning

confidence: 99%

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Anti-CD20 Treatment of Giant Cell Hepatitis With Autoimmune Hemolytic Anemia

Paganelli¹,

Patey

Bass

et al. 2014

Pediatrics

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Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare autoimmune disease of infancy characterized by severe liver disease associated with Coombs-positive hemolytic anemia. We recently showed that GCH-AHA is probably caused by a humoral immune mechanism. Such data support the use of rituximab, an anti-CD-20 monoclonal antibody specifically targeting B lymphocytes, as a treatment for GCH-AHA. We describe here the detailed clinical evolution of 4 children with GCH-AHA who showed a complete response to rituximab. All patients shared a severe course of the disease with poor control on standard and aggressive immunosuppression. Rituximab was well tolerated, and no side effects or infections were registered. Several doses were needed to induce remission, and 5 to 11 additional maintenance injections were necessary in the 2 more severe cases. Weaning from corticosteroids was achieved in all subjects. A steroid-sparing effect was noted in the 3 children who started rituximab early in the course of the disease. Overall, we show here that there is a strong rationale for treating GCH-AHA with rituximab. Early treatment could reduce the use of corticosteroids. Nevertheless, short-term steroids should be initially associated with rituximab to account for autoantibodies' half-life. Repeated injections are needed to treat and prevent relapses, but the best frequency and duration of treatment remain to be defined. Dr Paganelli conceptualized and designed the study, collected the data at one site, drafted the initial manuscript, and revised the manuscript; Dr Patey reviewed liver biopsies, provided the images, and revised the manuscript; Dr Bass collected the data at one site and revised the manuscript; Dr Alvarez conceptualized the study and critically reviewed the manuscript; and all authors approved the final manuscript as submitted. Giant cell hepatitis with autoimmune hemolytic anemia (GCH-AHA) is a rare disease affecting infants and young children, characterized by progressive liver disease with giant cell transformation associated with Coombs-positive hemolytic anemia. 1,2 Although autoantibodies are typically negative, Coombs positivity and the response to immunosuppressive treatment suggest that GCH-AHA is an autoimmune disease. Nevertheless, it is more difficult to control than autoimmune hepatitis (especially at onset), with only 70% of long-term survival with the native liver despite aggressive immunosuppression. 2 Treatment strategies include steroids, azathioprine, mycophenolate mofetil (MMF), calcineurin inhibitors, sirolimus, intravenous immunoglobulin (IVIg), cyclophosphamide, and splenectomy. [2][3][4][5][6] Empirical use of rituximab has been reported to treat GCH-AHA, with diverse results. 2,3,5,6 Coombs-positive AHA is well known to result from the activation of complement cascade on the red cell surface secondary to immunoglobulin G (IgG) binding. 7 We recently showed that hepatocyte injury in GCH-AHA is complement mediated and that the portal inflammatory infiltrate is constitut...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Anti-CD20 Treatment of Giant Cell Hepatitis With Autoimmune Hemolytic Anemia

Paganelli¹,

Patey

Bass

et al. 2014

Pediatrics

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“…This pathological entity is rare [1,2] . 27 cases have been reported in pediatric reviews [2,[4][5][6] . In 2011, an Italian pediatrician's team reported the biggest series of cases of this pathology.…”

Section: Discussionmentioning

confidence: 99%

“…Only 27 cases have been reported in pediatric reviews [2][3][4][5][6] . It usually presents as a severe hepatitis, jaundice and fever that begins about 1 year of age and is associated with AHA with a positive direct Coombs' test [3] .…”

Section: Introductionmentioning

confidence: 99%

Giant cell hepatitis with autoimmune hemolytic anemia in a nine month old infant

Bouguila¹,

Mabrouk²,

Tilouche³

et al. 2013

WJH

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Giant cell hepatitis (GCH) with autoimmune hemolytic anemia is a rare entity, limited to young children, with an unknown pathogenesis. We report the case of 9-mo old who presented with fever, diarrhea and jaundice four days before hospitalization. Physical examination found pallor, jaundice and hepatosplenomegaly. The laboratory workup showed serum total bilirubin at 101 μmol/L, conjugated bilirubin at 84 μmol/L, hemolytic anemia, thrombocytopenia and immunoglobulin G (IgG) and anti-C3d positive direct Coombs' test. The antinuclear, anti-smooth muscle and liver kidney microsomes 1 non-organ specific autoantibodies, antiendomisium antibodies were negative. Serological assays for viral hepatitis B and C, cytomegalovirus, herpes simplex and Epstein Barr virus were negative. The association of acute liver failure, Evan's syndrome, positive direct Coomb's test of mixed type (IgG and C3) and the absence of organ and non-organ specific autoantibodies suggested the diagnosis of GCH. The diagnosis was confirmed by a needle liver biopsy. The patient was treated by corticosteroids, immunomodulatory therapy and azathioprine but died with septicemia.

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