Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia

Melendez, Hector Vilca; Rela, Mohamed; Baker, Alastair; Ball, Colin; Portmann, B; Mieli‐Vergani, Giorgina; Heaton, Nigel

doi:10.1136/adc.77.3.249

Cited by 54 publications

(66 citation statements)

References 5 publications

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“…2 Response to standard immunosuppressive therapy is inadequate in most patients, and liver transplantation is complicated by a high rate of recurrence. 2,[10][11][12] The 4 cases presented here share a severe course of the disease with an incomplete response to both standard and aggressive immunosuppression.…”

Section: Discussionmentioning

confidence: 89%

“…Relapses after liver transplant are probably secondary to the lack of action of calcineurin inhibitors on humoral immunity. 10,11 A role of elevated serum B lymphocyte stimulator levels in inducing relapses has been hypothesized for rheumatoid arthritis and would be interesting to study in GCH-AHA. 16 Although the pathogenesis of relapses is not clear, the need for repeated injections of anti-CD20 to treat (and perhaps to prevent) relapses is clinically evident.…”

Section: Discussionmentioning

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: 89%

Section: Discussionmentioning

confidence: 99%

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

Paganelli¹,

Patey

Bass

et al. 2014

Pediatrics

View full text Add to dashboard Cite

show abstract

“…The liver biopsy in both of these patients showed characteristics giant cell transformation of the hepatocytes. It is thus possible that the syndrome described by Bernard et al and other researchers [1][2][3][4] is part of spectrum of manifestation of autoimmune hepatitis and not a distinct syndrome by itself.…”

Section: Discussionmentioning

confidence: 91%

“…Autoimmune hemolytic anemia associated with GCH is a rare entity [1][2][3][4]. Positive direct Coombs test is the only sign of autoimmunity in these patients.…”

Section: Discussionmentioning

confidence: 99%