Characteristics and outcomes of patients with hepatitis-associated aplastic anemia: Treatment approaches in the last decade
Characteristics and outcomes of patients with hepatitis-associated aplastic anemia: Treatment approaches in the last decade
Shiva Dianaty,1,*Erfan Shapourgan,2Zahra Purmajnun,3
1. Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran 2. Department of Medicine, Tehran University of Medical Science, Tehran, Iran 3. Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahrekord University, Shahrekord, Iran
Introduction: Hepatitis-associated aplastic anemia (HAAA) is a rare but well-recognized subtype of acquired aplastic anemia characterized by pancytopenia 1–3 months following an episode of acute hepatitis. In this syndrome, bone marrow failure results in a decrease in RBCs, WBCs, and platelets, followed by hepatitis as a result of decreased production. Other than drugs, toxins, and viral infections, aplastic anemia arises from an abnormal immune response. Acute hepatitis B-associated aplastic anemia is an extremely rare form of aplastic anemia. Typically, hepatitis is either idiopathic or caused by one or more hepatitis viruses, parvovirus B19, cytomegaloviruses, Epstein-Barr viruses, or toxins. The symptoms can range from fatigue to shortness of breath to increased susceptibility to infections caused by pancytopenia. Patients may also present with pallor, petechial rashes, ecchymosis, or signs of systemic infection on examination. The diagnosis is based on a prior history of hepatitis and pancytopenia in the complete blood count. A bone marrow biopsy typically indicates profound hypocellularity with morphologically normal residual hematopoietic cells in the absence of malignant infiltration and fibrosis. Since HAAA has a very poor prognosis, early detection is essential. For treating this syndrome, a variety of treatment options have been developed over the past decade based on each patient's condition.
Methods: The present study used scientific search by searching keywords and gathering related articles in databases including Science Direct, Google Scholar, and PubMed.
Results: There are a number of treatments for aplastic anemia that aim to achieve hematopoietic recovery, including immunosuppressive therapy (IST), thrombopoietin receptor agonists (TPO-RA), allogeneic stem cell transplantation (allo-HSCT), and anabolic hormones. Combining TPO-RA with immunotherapy along with cyclosporine and anti-thymocyte globulin is the most effective drug therapy. As a primary treatment option when a sibling with identical human leukocyte antigen (HLA) is available, allogeneic HSCT is often preferred. In the absence of a suitable donor, IST is an option that involves combining bone marrow stem cells from a sibling or cord blood stem cells from an unrelated donor. IST involves the use of immunosuppressive drugs, such as horse or rabbit antithymocyte globulins (ATG), antilymphocyte globulins (ALG), cyclosporine A (CsA), corticosteroids, and sometimes granulocyte colony-stimulating factor (G-CSF). An earlier study found that rATG was superior to horse ATG (hATG) in terms of effectiveness. As well as IST being effective post-transplantation, romiplostim, a thrombopoietin receptor agonist, and IST have been used effectively in the case of a child with severe HAAA who underwent liver transplantation. As well as platelet transfusions, coagulation factor replacement, and iron chelation therapy, supportive care measures are crucial in the early stages of this condition. A broad-spectrum antibiotic and antifungal should be considered first in pancytopenia. New treatments are being explored, including rituximab, which can be used in refractory cases, and thrombopoietin receptor agonists, such as eltrombopag, which can be used in conjunction with immunosuppressive therapy to improve outcomes. For hepatitis B-associated HAAA, lamivudine or tenofovir can be used, and for Epstein-Barr virus-induced aplastic anemia, acyclovir can be used. In EBV-associated HAAA, eltrombopag, an oral thrombopoietin receptor agonist, was prescribed along with an immunosuppressive regimen consisting of rATG and cyclosporine. The use of umbilical cord blood transplantation as well as haploidentical transplantation may be considered if the patient does not respond to IST. Aplastic anemia has been investigated for the potential of mesenchymal stromal cells (MSCs) derived from several sources, including the umbilical cord (UC). As UC-derived MSCs are considered safe and genetically stable, they are ideal for therapy applications. In pediatric patients with severe aplastic anemia, UC-MSCs can be effectively used as part of a treatment with drugs like CsA.
Conclusion: To conclude, HAAA treatments encompass a range of choices, with the choice dependent on factors such as donor availability and the subtype of the disease. There is a low transplant-related mortality rate with allogeneic HSCT for hepatitis-associated aplastic anemia. It is likely that emerging therapies will lead to improved outcomes for individuals with this challenging condition, including MSC-based treatments and CsA combinations. Further, results suggest that IST combined with TPO receptor agonists may provide an effective treatment option for patients suffering from HAA who are undergoing LDLT.