Parvovirus Associated Fulminant Hepatic Failure and Aplastic Anemia Treated Successfully With Liver and Bone Marrow Transplantation. A Report of Two Cases

Bathla, Lokesh; Grant, Wendy J.; Mercer, David F.; Vargas, Luciano; Gebhart, Catherine L.; Langnas, Alan Norman

doi:10.1111/ajt.12857

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…An increasing spectrum of clinical manifestation of B19V infection has been described ( Bathla et al 2014 ), including hepatitis, which is commonly caused by hepatotropic viruses (A-E) ( Hatakka et al 2011 , Rauff et al 2011 , Huang et al 2012 ). On the basis of its DNA detection in the liver of patients with acute liver failure (ALF) associated with BM aplasia and in the serum of patients with ALF of unknown aetiology, B19V has been implicated as an aetiological agent for ALF-associated aplastic anaemia ( Aoyagi et al 1987 , Langnas et al 1995 , Bernuau et al 1999 , Abe et al 2007 , Dwivedi et al 2009 , Huang et al 2012 , Bathla et al 2014 ).…”

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confidence: 99%

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

Leon

Marchevsky

Gaspar

et al. 2016

Mem. Inst. Oswaldo Cruz

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This study was conducted to analyse the course and the outcome of the liver disease in the co-infected animals in order to evaluate a possible synergic effect of human parvovirus B19 (B19V) and hepatitis A virus (HAV) co-infection. Nine adult cynomolgus monkeys were inoculated with serum obtained from a fatal case of B19V infection and/or a faecal suspension of acute HAV. The presence of specific antibodies to HAV and B19V, liver enzyme levels, viraemia, haematological changes, and necroinflammatory liver lesions were used for monitoring the infections. Seroconversion was confirmed in all infected groups. A similar pattern of B19V infection to human disease was observed, which was characterised by high and persistent viraemia in association with reticulocytopenia and mild to moderate anaemia during the period of investigation (59 days). Additionally, the intranuclear inclusion bodies were observed in pro-erythroblast cell from an infected cynomolgus and B19V Ag in hepatocytes. The erythroid hypoplasia and decrease in lymphocyte counts were more evident in the co-infected group. The present results demonstrated, for the first time, the susceptibility of cynomolgus to B19V infection, but it did not show a worsening of liver histopathology in the co-infected group.

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confidence: 99%

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

Leon

Marchevsky

Gaspar

et al. 2016

Mem. Inst. Oswaldo Cruz

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“…15 Subsequent reports demonstrated better success with allogeneic bone marrow transplantation, and this remains the best therapeutic modality in patients with available donors. 16 Our group has previously described the successful use of bone marrow stem cells and liver allograft from the same related donor in a similar case of HAAA. 17 HSCT after solid organ transplantation (SOT) is fraught with the interplay of numerous clinical and immunological variables making a combined interdisciplinary approach essential.…”

Section: Discussion and Re Vie W Of Liter Aturementioning

confidence: 99%

“…There is no standardised guideline in the post‐LT setting, with reports of treatments consisting of immunosuppression with corticosteroids, cyclosporine and/or anti‐thymocyte globulin . Subsequent reports demonstrated better success with allogeneic bone marrow transplantation, and this remains the best therapeutic modality in patients with available donors . Our group has previously described the successful use of bone marrow stem cells and liver allograft from the same related donor in a similar case of HAAA …”

Section: Discussion and Review Of Literaturementioning

confidence: 99%

Sequential liver and haematopoietic stem cell transplantation in a case of fulminant hepatitis associated liver failure and aplastic anaemia

Al‐Shaibani

Kotha

Lam

et al. 2019

European J of Haematology

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Hepatitis-associated aplastic anaemia (HAAA) is a potentially lethal complication of acute hepatitis where pancytopenia develops a few months after the acute hepatitis episode. As with severe aplastic anaemia (SAA), the pathogenic mechanism is thought to be immune-mediated destruction of haematopoietic stem cells (HSCs) leading to bone marrow failure and pancytopenia. Acute hepatitis may progress to fulminant hepatic failure (FHF) necessitating liver transplantation as a life-saving measure. The optimal management of SAA in young patients is an allogeneic haematopoietic stem cell transplantation (HSCT) from a suitably matched donor. Both modalities are associated with considerable morbidity.We present the case of a patient treated with deceased donor liver transplantation for FHF secondary to acute hepatitis who subsequently developed SAA that was successfully treated with a matched unrelated donor (MUD) allogeneic HSCT. To our knowledge, this is the first reported adult case of post-liver transplant SAA treated with MUD HSCT. | C A S E REP ORTA previously healthy 19-year-old female presented with jaundice, lethargy and abdominal pain in October 2017. Initial laboratory analysis revealed elevated aspartate aminotransferase (AST) 1809 U/L, alanine aminotransferase (ALT) 2303 U/L, bilirubin 505 μmol/L and INR 1.54. Complete blood count and renal function were normal with haemoglobin (Hb) 133 g/L, white blood count (WBC) Abstract The management of severe aplastic anaemia is particularly challenging when it occurs in the context of recent liver transplantation. Rapid identification of a suitable donor followed by allogeneic haematopoietic stem cell transplantation is the only curative option. This scenario is often complicated by potentially life-threatening infections that develop as a consequence of immunosuppression. Alternative donor transplantation using suitably matched unrelated donors can be potentially life-saving when suitably matched sibling donors are unavailable. Above all, a dedicated interdisciplinary approach with seamless communication between hepatology, transplant surgery, haematology, and stem cell transplant services is essential to achieving optimaloutcomes. Herein, we describe a case of severe hepatitis leading to hepatic failure who was treated with liver transplantation from a deceased donor, and later received an allogeneic haematopoietic stem cell transplantation from a matched unrelated donor for hepatitis-associated aplastic anaemia. K E Y W O R D Sallogeneic blood and marrow transplantation, aplastic anaemia, liver transplantation

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“…Many hypotheses for disease pathogenesis center on the direct infection of HSCs, viral recognition by HSCs via PRRs, inflammation-mediated effects by surrounding cells or response to changes in the stem cell microenvironment ( 15 , 19 , 20 , 44 ). Cytomegalovirus (CMV), parvovirus B19, and the Epstein–Barr virus (EBV) induce HSC injury through direct toxic effects from pathogens ( 14 , 45 ). However, the majority of pathogen-related cases are thought to be due to the excessive activation of immune effector cells, leading to an overwhelming release of myelosuppressive cytokines and negative proliferation signaling to HSCs (Table 1 ).…”

Section: Bm Failure Induced By Microbial Infectionmentioning

confidence: 99%

Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes

2017

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Acquired bone marrow failure syndromes encompass a unique set of disorders characterized by a reduction in the effective production of mature cells by the bone marrow (BM). In the majority of cases, these syndromes are the result of the immune-mediated destruction of hematopoietic stem cells or their progenitors at various stages of differentiation. Microbial infection has also been associated with hematopoietic stem cell injury and may lead to associated transient or persistent BM failure, and recent evidence has highlighted the potential impact of commensal microbes and their metabolites on hematopoiesis. We summarize the interactions between microorganisms and the host immune system and emphasize how they may impact the development of acquired BM failure.

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Parvovirus Associated Fulminant Hepatic Failure and Aplastic Anemia Treated Successfully With Liver and Bone Marrow Transplantation. A Report of Two Cases

Cited by 15 publications

References 27 publications

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

Cynomolgus monkeys (Macaca fascicularis) experimentally infected with B19V and hepatitis A virus: no evidence of the co-infection as a cause of acute liver failure

Sequential liver and haematopoietic stem cell transplantation in a case of fulminant hepatitis associated liver failure and aplastic anaemia

Microbe-Induced Inflammatory Signals Triggering Acquired Bone Marrow Failure Syndromes

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