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Albostani A, Haj Ahmad NA, Aljnidy N, Batal H, Hamdan O. Acute hepatitis A-associated aplastic anemia in a pediatric: a case report from Syria. Ann Med Surg (Lond) 2025; 87:2406-2410. [PMID: 40212128 PMCID: PMC11981424 DOI: 10.1097/ms9.0000000000003107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 02/16/2025] [Indexed: 04/13/2025] Open
Abstract
Introduction and importance Hepatitis A virus is typically an acute infection that is often asymptomatic, especially in children. In Syria, hepatitis A virus infections are not uncommon. However, the emergence of extrahepatic manifestations, such as aplastic anemia, following hepatitis A infection is unpredictable and challenging to manage, with the connection between these conditions remaining poorly understood. This paper aims to highlight this rare manifestation of aplastic anemia linked to hepatitis A infection in children. Case presentation We report a rare case of hepatitis-associated aplastic anemia in a 3-year-old Syrian boy who exhibited symptoms of fever, bruising, and mucosal bleeding 1 month after the onset of acute hepatitis. The diagnosis was confirmed via bone marrow examination, and he was treated with immunosuppressives, resulting in full recovery after a year of follow-up with no need for bone marrow transplantation. Clinical discussion Hepatitis A infection associated with aplastic anemia is an extremely rare condition. Its etiology might be related to the immune system, and its diagnosis is always confirmed with bone marrow biopsy. Treatment includes hematopoietic cell transplantation if the immunosuppressive therapy is not effective. Further research is essential to understand the mechanisms and optimize treatment options. Conclusion Awareness of the potential association between hepatitis A and aplastic anemia is essential for early diagnosis and effective management. More studies are required to enhance our understanding of the condition and improve therapeutic approaches.
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Affiliation(s)
| | | | - Noura Aljnidy
- Faculty of Medicine, University of Aleppo, Aleppo, Syria
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Enache A, Carty SA, Babushok DV. Origins of T-cell-mediated autoimmunity in acquired aplastic anaemia. Br J Haematol 2025; 206:1035-1053. [PMID: 39836983 PMCID: PMC11985373 DOI: 10.1111/bjh.19993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Accepted: 12/28/2024] [Indexed: 01/23/2025]
Abstract
Acquired aplastic anaemia (AA) is an autoimmune bone marrow failure disease resulting from a cytotoxic T-cell-mediated attack on haematopoietic stem and progenitor cells (HSPCs). Despite significant progress in understanding the T-cell repertoire alterations in AA, identifying specific pathogenic T cells in AA patients has remained elusive, primarily due to the unknown antigenic targets of the autoimmune attack. In this review, we will synthesize findings from several decades of research to critically evaluate the current knowledge on T-cell repertoires in AA. We will highlight new insights gained from recent in vitro studies of candidate autoreactive T cells isolated from AA patients and will discuss efforts to identify shared T-cell clonotypes in AA. Finally, we will discuss emerging evidence on the potential T-cell cross-reactivity between HSPC and common viral epitopes that may contribute to the development of AA in some patients. We conclude by highlighting the areas of consensus and limitations, as well as the ongoing uncertainties, and we identify promising directions for future research in the field.
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MESH Headings
- Anemia, Aplastic/genetics
- Anemia, Aplastic/immunology
- Autoimmunity/genetics
- Autoimmune Diseases/genetics
- Autoimmune Diseases/immunology
- Hematopoietic Stem Cells/immunology
- Epitopes, T-Lymphocyte/immunology
- Antigens, Viral/immunology
- Immune Tolerance
- Receptors, Antigen, T-Cell/genetics
- Receptors, Antigen, T-Cell/immunology
- Lymphocyte Activation
- Humans
- Gene Rearrangement, T-Lymphocyte
- T-Lymphocytes, Cytotoxic/immunology
- Viruses/immunology
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Affiliation(s)
- Aura Enache
- Drexel University College of MedicineDrexel UniversityPhiladelphiaPennsylvaniaUSA
- Division of Hematology‐Oncology, Department of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
| | - Shannon A. Carty
- Division of Hematology and Oncology, Department of Internal MedicineUniversity of MichiganAnn ArborMichiganUSA
| | - Daria V. Babushok
- Division of Hematology‐Oncology, Department of MedicineUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA
- Comprehensive Bone Marrow Failure Center, Department of PediatricsChildren's Hospital of PhiladelphiaPhiladelphiaPennsylvaniaUSA
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3
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Schmutz M, Chartier S, Leblanc T, Mussini C, Gardin A, Gonzales E, Roque-Afonso AM, Le Cam S, Hery G, Neven B, Charbel R, Vartanian JP, Jacquemin E, Morelle G, Almes M. Increased incidence of seronegative autoimmune hepatitis in children during SARS-CoV-2 pandemia period. Front Immunol 2024; 15:1445610. [PMID: 39328418 PMCID: PMC11425678 DOI: 10.3389/fimmu.2024.1445610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Accepted: 08/12/2024] [Indexed: 09/28/2024] Open
Abstract
Background Seronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARS-CoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger. Methods We conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022. Results Thirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients' clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before. Conclusion In cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement.
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Affiliation(s)
- Muriel Schmutz
- Pediatric Hepatology and Pediatric Liver Transplant Department, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, European Reference Networks (ERN) RARE LIVER, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Suzanne Chartier
- Pathology Department, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Thierry Leblanc
- Department of Pediatric Hematology and Immunology, AP-HP, Université Paris Cité Paris, Robert Debré Hospital, Paris, France
| | - Charlotte Mussini
- Pathology Department, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Antoine Gardin
- Pediatric Hepatology and Pediatric Liver Transplant Department, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, European Reference Networks (ERN) RARE LIVER, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
- INSERM Unité Mixte de Recherche (UMR)-S 1193, Paris-Saclay University, Hépatinov, Orsay, France
- European Reference Networks (ERN) Rare Liver, Hamburg, Germany
| | - Emmanuel Gonzales
- Pediatric Hepatology and Pediatric Liver Transplant Department, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, European Reference Networks (ERN) RARE LIVER, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
- INSERM Unité Mixte de Recherche (UMR)-S 1193, Paris-Saclay University, Hépatinov, Orsay, France
- European Reference Networks (ERN) Rare Liver, Hamburg, Germany
| | - Anne-Marie Roque-Afonso
- INSERM Unité Mixte de Recherche (UMR)-S 1193, Paris-Saclay University, Hépatinov, Orsay, France
- Virology Department, National Reference Center for Hepatitis A virus, Paul Brousse Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Villejuif, France
| | - Solene Le Cam
- Pediatric Radiology Department, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Geraldine Hery
- Department of Paediatric Surgery, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Benedicte Neven
- Pediatric Hematology-Immunology and Rheumatology Department, AP-HP, Université Paris Cité Paris, Necker-Children’s Hospital, Paris, France
- INSERM Unité Mixte de Recherche (UMR) 1163, Imagine Institute, Paris, France
| | - Ramy Charbel
- Pediatric Intensive Care Unit, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Jean-Pierre Vartanian
- Virus and Cellular Stress Unit, Department of Virology, Institut Pasteur, Université de Paris Cité, Paris, France
| | - Emmanuel Jacquemin
- Pediatric Hepatology and Pediatric Liver Transplant Department, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, European Reference Networks (ERN) RARE LIVER, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
- INSERM Unité Mixte de Recherche (UMR)-S 1193, Paris-Saclay University, Hépatinov, Orsay, France
- European Reference Networks (ERN) Rare Liver, Hamburg, Germany
| | - Guillaume Morelle
- Centre for Haemophilia and Constitutional Bleeding Disorders, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
- Department of Pediatric Emergency, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
| | - Marion Almes
- Pediatric Hepatology and Pediatric Liver Transplant Department, Reference Center for Biliary Atresia and Genetic Cholestasis, FSMR FILFOIE, European Reference Networks (ERN) RARE LIVER, AP-HP, Paris-Saclay University, Bicêtre Hospital, Kremlin-Bicêtre, France
- INSERM Unité Mixte de Recherche (UMR)-S 1193, Paris-Saclay University, Hépatinov, Orsay, France
- European Reference Networks (ERN) Rare Liver, Hamburg, Germany
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Mercedes R, Harpavat S, Hertel PM, Sasa G, Kirk S, Patel K, Mysore KR. Herbal and dietary supplement induced liver injury leading to hepatitis-associated severe aplastic anemia: A case report. JPGN REPORTS 2024; 5:208-212. [PMID: 38756121 PMCID: PMC11093934 DOI: 10.1002/jpr3.12041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 11/28/2023] [Accepted: 12/24/2023] [Indexed: 05/18/2024]
Abstract
Herbal and dietary supplements (HDS) are a common etiology of drug induced liver injury and, specifically, Herbalife® supplements have been implicated. Hepatitis associated aplastic anemia (HAAA) is a rare and potentially fatal complication after acute hepatitis characterized by pancytopenia. While there have been rare cases of HDS leading to HAAA, no cases of Herbalife® induced liver injury leading to HAAA have been reported from this specific HDS. We report a unique case of severe aplastic anemia developing after sub-fulminant liver failure associated with chronic HDS use. This case illustrates the importance of warning the public about HDS as their use continues to increase. It is not only important to recognize HDS as etiology, but also for healthcare providers to carefully monitor these patients after resolution of liver injury for the development of HAAA.
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Affiliation(s)
- Rebecca Mercedes
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of MedicineTexas Children's HospitalHoustonTexasUSA
| | - Sanjiv Harpavat
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of MedicineTexas Children's HospitalHoustonTexasUSA
| | - Paula M. Hertel
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of MedicineTexas Children's HospitalHoustonTexasUSA
| | - Ghadir Sasa
- Division of Hematology‐Oncology, Department of Pediatrics, Baylor College of MedicineTexas Children's HospitalHoustonTexasUSA
| | - Susan Kirk
- Division of Hematology‐Oncology, Department of Pediatrics, Baylor College of MedicineTexas Children's HospitalHoustonTexasUSA
| | - Kalyani Patel
- Department of Pathology and ImmunologyBaylor College of MedicineHoustonTexasUSA
| | - Krupa R. Mysore
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Baylor College of MedicineTexas Children's HospitalHoustonTexasUSA
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Songtanin B, Chaisrimaneepan N, Mendóza R, Nugent K. Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections. Viruses 2024; 16:618. [PMID: 38675959 PMCID: PMC11055091 DOI: 10.3390/v16040618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2024] [Revised: 04/11/2024] [Accepted: 04/13/2024] [Indexed: 04/28/2024] Open
Abstract
Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.
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Affiliation(s)
- Busara Songtanin
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA (K.N.)
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Fu L, Zhang J, Wang R, Yang B, Li H, Chen H, Ma J. Clinical characteristics of hepatitis-associated aplastic anemia in children. Ann Hematol 2024; 103:397-404. [PMID: 38082101 DOI: 10.1007/s00277-023-05566-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Accepted: 11/22/2023] [Indexed: 01/23/2024]
Abstract
To understand the current situation of hepatitis-related aplastic anemia (HAAA) in children, we analyzed the patients with HAAA admitted to our hospital in the past 5 years to understand the disease characteristics and prognosis. The clinical data of patients with HAAA admitted to our hospital from February 2017 to May 2022 were retrospectively analyzed. A total of 81 patients with HAAA, 56 males and 25 females. The median onset age was 5.9 years. The median time from hepatitis to occurrence of hemocytopenia was 30 days, and the median follow-up time was 2.77 years. There were 23 cases (28.5%) of severe aplastic anemia (SAA), 50 cases of very severe aplastic anemia (VSAA), and 8 cases of non-severe aplastic anemia (NSAA). At the beginning of the disease, cytotoxic T lymphocyte (CTL) was higher than normal in 60% of patients, and the median CD4/CD8 ratio was 0.2. As of follow-up, 72 children survived, 4 were lost, and 5 died. Thirty-four cases were treated with immunosuppressive therapy (IST), with a median follow-up time of 0.97 years. The total reaction rate was 73.5% (25/34), the complete reaction rate was 67.6% (23/34), and the nonreaction rate was 26.5% (9/34). Multivariate analysis suggested that co-infection was an independent risk factor affecting the efficacy of IST at 6 months, with an OR value of 16.76, 95% CI (1.23, 227.95), P=0.034. No independent influencing factors were found at the end of follow-up. The proportion of CTL cells in peripheral blood of children with HAAA is relatively increased, and IST is effective in 73.5% of children. Co-infection may prolongs the time to response to IST.
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Affiliation(s)
- Lingling Fu
- Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Jialu Zhang
- Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Ruixin Wang
- Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Bixi Yang
- Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Hongmin Li
- Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China
| | - Hui Chen
- Hematologic Disease Laboratory, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, 100045, China
| | - Jie Ma
- Hematology Center, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.
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Nastasio S, Mosca A, Alterio T, Sciveres M, Maggiore G. Juvenile Autoimmune Hepatitis: Recent Advances in Diagnosis, Management and Long-Term Outcome. Diagnostics (Basel) 2023; 13:2753. [PMID: 37685291 PMCID: PMC10486972 DOI: 10.3390/diagnostics13172753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/11/2023] [Accepted: 08/13/2023] [Indexed: 09/10/2023] Open
Abstract
Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance. Recent evidence however suggests that treatment discontinuation is possible after a prolonged period of normal aminotransferase activity without the need for liver biopsy prior to withdrawal.
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Affiliation(s)
- Silvia Nastasio
- Division of Gastroenterology, Hepatology & Nutrition, Boston Children’s Hospital and Harvard Medical School, Boston, MA 02115, USA;
| | - Antonella Mosca
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.M.); (T.A.)
| | - Tommaso Alterio
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.M.); (T.A.)
| | - Marco Sciveres
- Pediatric Department and Transplantation, ISMETT, 90133 Palermo, Italy;
| | - Giuseppe Maggiore
- Hepatogastroenterology, Rehabilitative Nutrition, Digestive Endoscopy and Liver Transplant Unit, ERN RARE LIVER, Bambino Gesù Children’s Hospital, IRCCS, 00165 Rome, Italy; (A.M.); (T.A.)
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8
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Marginean CM, Pirscoveanu D, Popescu M, Docea AO, Radu A, Popescu AIS, Vasile CM, Mitrut R, Marginean IC, Iacob GA, Firu DM, Mitrut P. Diagnostic Approach and Pathophysiological Mechanisms of Anemia in Chronic Liver Disease—An Overview. GASTROENTEROLOGY INSIGHTS 2023; 14:327-341. [DOI: 10.3390/gastroent14030024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
Hematological abnormalities are frequently linked to chronic liver disease of any etiology. About 75% of patients with advanced chronic liver disease experience anemia. The causes of anemia are complex and multifactorial, particularly in cirrhotic patients. Acute and long-term blood loss from the upper gastrointestinal tract, malnutrition, an enlarged spleen brought on by portal hypertension, hemolysis, and coagulation issues are the main causes of anemia. Alcohol, a common cause of chronic liver disease, determines anemia through direct toxicity on the bone marrow, with the suppression of hematopoiesis, through vitamin B6, B12, and folate deficiency due to low intake and malabsorption. In patients with chronic hepatitis C virus infection, antiviral drugs such as pegylated interferon and ribavirin can also cause significant anemia. The use of interferon has been linked to bone marrow toxicity, and hemolytic anemia brought on by ribavirin is a well-known dose-dependent side effect. Within six months of the infection with hepatitis B, hepatitis C, and Epstein–Barr viruses, aplastic anemia associated with hepatitis is seen. This anemia is characterized by pancytopenia brought on by hypocellular bone marrow. Esophageal varices, portal hypertensive gastropathy, and gastric antral vascular ectasia can all cause acute and chronic blood loss. These conditions can progress to iron deficiency anemia, microcytic anemia, and hypochromic anemia. Another common hematologic abnormality in liver cirrhosis is macrocytosis, with multifactorial causes. Vitamin B12 and folate deficiency are frequent in liver cirrhosis, especially of alcoholic etiology, due to increased intestinal permeability, dysbiosis, and malnutrition. Many chronic liver diseases, like viral and autoimmune hepatitis, have a chronic inflammatory substrate. Proinflammatory cytokines, including tumor necrosis factor and interleukin 1, 6, and 10, are the main factors that diminish iron availability in progenitor erythrocytes and subsequent erythropoiesis, leading to the development of chronic inflammatory, normochromic, normocytic anemia.
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Affiliation(s)
- Cristina Maria Marginean
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Denisa Pirscoveanu
- Department of Neurology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Mihaela Popescu
- Department of Endocrinology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Antonia Radu
- Department of Pharmaceutical Botany, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | | | - Corina Maria Vasile
- Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital, 33600 Pessac, France
| | - Radu Mitrut
- Department of Cardiology, University and Emergency Hospital, 050098 Bucharest, Romania
| | | | - George Alexandru Iacob
- Faculty of Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Dan Mihai Firu
- Department of Medical Semiology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Paul Mitrut
- Department of Internal Medicine, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
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Wang Y, Li J, Pang AM, Yang DL, Chen X, Zhang RL, Wei JL, Ma QL, Zhai WH, He Y, Jiang EL, Han MZ, Feng SZ. [Efficacy and safety of allogeneic hematopoietic stem cell transplantation in the treatment of 28 patients with hepatitis-related aplastic anemia]. ZHONGHUA XUE YE XUE ZA ZHI = ZHONGHUA XUEYEXUE ZAZHI 2023; 44:628-634. [PMID: 37803835 PMCID: PMC10520222 DOI: 10.3760/cma.j.issn.0253-2727.2023.08.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Indexed: 10/08/2023]
Abstract
Objective: To evaluate the efficacy and safety of HLA-haploidentical hematopoietic stem cell transplantation (allo-HSCT) for hepatitis-related aplastic anemia (HRAA) patients. Methods: Retrospective analysis was performed on hepatitis-associated aplastic anemia patients who received haplo-HSCT at our center between January 2012 and June 2022. October 30, 2022 was the final date of follow-up. Results: This study included 28 HRAA patients receiving allo-HSCT, including 18 males (64.3% ) and 10 females (35.7% ), with a median age of 25.5 (9-44) years. About 17 cases of severe aplastic anemia (SAA), 10 cases of very severe aplastic anemia (VSAA), and 1 case of transfusion-dependent aplastic anemia (TD-NSAA) were identified. Among 28 patients, 15 patients received haplo-HSCT, and 13 received MSD-HSCT. The 2-year overall survival (OS) rate, the 2-year failure-free survival (FFS) rate, the 2-year transplant-related mortality (TRM) rate, the 100-day grade Ⅱ-Ⅳ acute graft-versus-host disease (aGVHD) cumulative incidence rate, and the 2-year chronic graft-versus-host disease (cGVHD) cumulative incidence rate were 81.4%, 81.4% (95% CI 10.5% -20.6% ), 14.6% (95% CI 5.7% -34.3% ), 25.0% (95% CI 12.8% -45.4% ), and 4.2% (95% CI 0.6% -25.4% ), respectively. After transplantation, all patients had no significant liver function damage. Compared with the MSD-HSCT group, only the incidence of cytomegaloviremia was significantly higher in the haplo-HSCT group [60.0% (95% CI 35.2% -84.8% ) vs 7.7% (95% CI 0-22.2% ), P=0.004]. No statistically significant difference in the Epstein-Barr virus was found in the 2-year OS, 2-year FFS, 2-year TRM, and 100-day grade Ⅱ-Ⅳ aGVHD cumulative incidence rates and 2-year cGVHD cumulative incidence rate. Conclusion: Allo-HSCT is safe and effective for HRAA, and haplo-HSCT can be used as a safe and effective alternative for newly diagnosed HRAA patients who cannot obtain HLA-matched sibling donors.
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Affiliation(s)
- Y Wang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China Yantai Yuhuangding Hospital, Yantai 264000, China
| | - J Li
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - A M Pang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - D L Yang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - X Chen
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - R L Zhang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - J L Wei
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Q L Ma
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - W H Zhai
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - Y He
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - E L Jiang
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - M Z Han
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
| | - S Z Feng
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China Tianjin Institutes of Health Science, Tianjin 301600, China
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10
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Braudeau C, Delbos L, Couec ML, Danic G, Chevreuil J, Lecuroux C, Grain A, Eveillard M, Rialland F, Sicre de Fontbrune F, Beriou G, Degauque N, Michonneau D, Josien R, de Latour RP, Thomas C, Martin JC. System-level immune monitoring reveals new pathophysiological features in hepatitis-associated aplastic anemia. Blood Adv 2023; 7:4039-4045. [PMID: 37267438 PMCID: PMC10410176 DOI: 10.1182/bloodadvances.2022008224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 05/16/2023] [Accepted: 05/20/2023] [Indexed: 06/04/2023] Open
Affiliation(s)
- Cecile Braudeau
- Laboratoire d’Immunologie, CHU Nantes, Centre d’Immunomonitorage Nantes Atlantique, Nantes Université, Nantes, France
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - Laurence Delbos
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - Marie-Laure Couec
- CHU Nantes, Service d'Oncologie-Hématologie et Immunologie Pédiatrique, Nantes Université, Nantes, France
| | - Gwenvael Danic
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - Justine Chevreuil
- Laboratoire d’Immunologie, CHU Nantes, Centre d’Immunomonitorage Nantes Atlantique, Nantes Université, Nantes, France
| | - Camille Lecuroux
- Laboratoire d’Immunologie, CHU Nantes, Centre d’Immunomonitorage Nantes Atlantique, Nantes Université, Nantes, France
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - Audrey Grain
- CHU Nantes, Service d'Oncologie-Hématologie et Immunologie Pédiatrique, Nantes Université, Nantes, France
| | - Marion Eveillard
- Laboratoire d’Hematologie, CHU Nantes, Nantes Université, Nantes, France
| | - Fanny Rialland
- CHU Nantes, Service d'Oncologie-Hématologie et Immunologie Pédiatrique, Nantes Université, Nantes, France
| | | | - Gaelle Beriou
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - Nicolas Degauque
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - David Michonneau
- Hematology Transplantation, Saint-Louis Hospital, Paris, France
- Université Paris Cité, INSERM U976, Paris, France
| | - Regis Josien
- Laboratoire d’Immunologie, CHU Nantes, Centre d’Immunomonitorage Nantes Atlantique, Nantes Université, Nantes, France
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
| | - Régis Peffault de Latour
- Hematology Transplantation, Saint-Louis Hospital, Paris, France
- Université Paris Cité, INSERM U976, Paris, France
- Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria, Saint-Louis Hospital, Paris, France
| | - Caroline Thomas
- CHU Nantes, Service d'Oncologie-Hématologie et Immunologie Pédiatrique, Nantes Université, Nantes, France
| | - Jerome C. Martin
- Laboratoire d’Immunologie, CHU Nantes, Centre d’Immunomonitorage Nantes Atlantique, Nantes Université, Nantes, France
- CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, UMR 1064, Institut de transplantation urologie-néphrologie, Nantes Université, Nantes, France
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11
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Islek A, Tumgor G. Seronegative autoimmune hepatitis in childhood. World J Clin Pediatr 2023; 12:77-85. [PMID: 37342447 PMCID: PMC10278082 DOI: 10.5409/wjcp.v12.i3.77] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Revised: 04/26/2023] [Accepted: 05/08/2023] [Indexed: 06/08/2023] Open
Abstract
Comprehensive guidelines on seropositive autoimmune hepatitis have been published for both adults and children, although these guidelines comprise only limited knowledge about seronegative autoimmune hepatitis. Autoimmune hepatitis presents as an acute or chronic progressive disease and poor outcomes are inevitable if left untreated. The absence of autoantibody positivity, hypergammaglobulinemia and lack of comprehensive algorithms makes seronegative autoimmune hepatitis a mysterious disease. In general, seronegative autoimmune hepatitis often presents with acute hepatitis, and its treatment and prognosis similar to seropositive autoimmune hepatitis. The present review focuses on the known characteristics of seronegative autoimmune hepatitis in childhood, and those of which current knowledge is vague.
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Affiliation(s)
- Ali Islek
- Department of Pediatric Gastroenterology, Cukurova University School of Medicine, Adana 01320, Turkey
| | - Gokhan Tumgor
- Department of Pediatric Gastroenterology, Cukurova University School of Medicine, Adana 01320, Turkey
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12
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Zhang X, Yang W, Yang D, Wei J, Zhang P, Feng S, Jiang E, Zhang L, He Y, Zhang F, Han M. Comparison of hematopoietic stem cell transplantation and immunosuppressive therapy as the first-line treatment option for patients with severe hepatitis−associated aplastic anemia. Front Immunol 2023; 14:1146997. [PMID: 37006284 PMCID: PMC10063874 DOI: 10.3389/fimmu.2023.1146997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Accepted: 03/06/2023] [Indexed: 03/19/2023] Open
Abstract
Hepatitis-associated aplastic anemia (HAAA) is a rare variant of acquired aplastic anemia characterized with a syndrome of bone marrow failure after hepatitis. We retrospectively analyzed the outcomes of consecutive severe HAAA patients who received immunosuppressive therapy (IST, n = 70), matched-sibling donor hematopoietic stem cell transplantation (MSD-HSCT, n = 26) or haploidentical-donor (HID) HSCT (n = 11) as the first-line treatment. In the IST group, the hematologic response (HR) rate was 55.71% at 6 months. In contrast, HSCT recipients exhibited significantly more rapid and sustained hematopoiesis (HR 76.92%, 96.15% and 96.15% at 3, 6 and 12months, respectively). The 5-year overall survival (OS) was not different among IST (83.7 ± 4.9%), MSD-HSCT (93.3 ± 6.4%) and HID-HSCT group (80.8 ± 12.3%). Compared with IST, MSD and HID-HSCT demonstrated a trend of superiority in the estimated 5-year failure-free survival rates (93.3 ± 6.4% vs 64.3 ± 6.0%, p = 0.05; 80.8 ± 12.3% vs 64.3 ± 6.0%, p = 0.57). In subsequent stratified analysis on age, we found that HID-HSCT showed its efficacy and safety among young patients. In sum, MSD-HSCT remains first-line treatment choice for HAAA, whereas HID-HSCT represents an alternative treatment choice in addition to IST for young patients (< 40 years) without a matched sibling donor.
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Affiliation(s)
- Xiaoyu Zhang
- Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Wenrui Yang
- Tianjin Institutes of Health Science, Tianjin, China
- Anemia Therapeutic Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Donglin Yang
- Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Jialin Wei
- Tianjin Institutes of Health Science, Tianjin, China
- Anemia Therapeutic Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Ping Zhang
- Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, United States
| | - Sizhou Feng
- Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Erlie Jiang
- Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Li Zhang
- Tianjin Institutes of Health Science, Tianjin, China
- Anemia Therapeutic Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- *Correspondence: Li Zhang, ; Yi He,
| | - Yi He
- Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
| | - Fengkui Zhang
- Tianjin Institutes of Health Science, Tianjin, China
- Anemia Therapeutic Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
| | - Mingzhe Han
- Stem Cell Transplantation Center, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China
- Tianjin Institutes of Health Science, Tianjin, China
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13
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Chen RL, Ip PP, Shaw JJ, Wang YH, Fan LH, Shen YL, Joseph NA, Chen TE, Chen LY. Anti-Thymocyte Globulin (ATG)-Free Nonmyeloablative Haploidentical PBSCT Plus Post-Transplantation Cyclophosphamide Is a Safe and Efficient Treatment Approach for Pediatric Acquired Aplastic Anemia. Int J Mol Sci 2022; 23:ijms232315192. [PMID: 36499545 PMCID: PMC9739033 DOI: 10.3390/ijms232315192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/29/2022] [Accepted: 11/30/2022] [Indexed: 12/11/2022] Open
Abstract
Most cases of acquired aplastic anemia (AA) arise from autoimmune destruction of hematopoietic stem and progenitor cells. Human leukocyte antigen (HLA)-haploidentical nonmyeloablative hematopoietic stem cell transplantation (HSCT) plus post-transplantation cyclophosphamide (PTCy) is increasingly applied to salvage AA using bone marrow as graft and anti-thymocyte globulin (ATG) in conditioning. Herein, we characterize a cohort of twelve AA patients clinically and molecularly, six who possessed other immunological disorders (including two also carrying germline SAMD9L mutations). Each patient with SAMD9L mutation also carried an AA-related rare BCORL1 variant or CTLA4 p.T17A GG genotype, respectively, and both presented short telomere lengths. Six of the ten patients analyzed harbored AA-risky HLA polymorphisms. All patients recovered upon non-HSCT (n = 4) or HSCT (n = 8) treatments. Six of the eight HSCT-treated patients were subjected to a modified PTCy-based regimen involving freshly prepared peripheral blood stem cells (PBSC) as graft and exclusion of ATG. All patients were engrafted between post-transplantation days +13 and +18 and quickly reverted to normal life, displaying a sustained complete hematologic response and an absence of graft-versus-host disease. These outcomes indicate most AA cases, including of the SAMD9L-inherited subtype, are immune-mediated and the modified PTCy-based regimen we present is efficient and safe for salvage.
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Affiliation(s)
- Rong-Long Chen
- Department of Pediatric Hematology and Oncology, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, Taiwan
- Correspondence:
| | - Peng Peng Ip
- Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan
| | - Jy-juinn Shaw
- School of Law, National Yang Ming Chiao Tung University, Hsinchu City 30093, Taiwan
| | - Yun-Hsin Wang
- Department of Chemistry, Tamkang University, Tamsui, New Taipei City 251301, Taiwan
| | - Li-Hua Fan
- Department of Pharmacy, Koo Foundation Sun Yat-sen Cancer Center, Taipei 11259, Taiwan
| | - Yi-Ling Shen
- Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan
| | - Nithila A. Joseph
- Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan
| | - Tsen-Erh Chen
- Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan
| | - Liuh-Yow Chen
- Institute of Molecular Biology, Academia Sinica, Taipei 115024, Taiwan
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14
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Ghanei-Shahmirzadi A, Reihani H, Abbasi-Kashkooli A, Karbasian F, Hedayati SB, Bordbar M, Ataollahi M, Dehghani SM, Geramizadeh B. Aplastic anemia: a new complication in the recent mysterious hepatitis outbreak among children worldwide: two case reports. J Med Case Rep 2022; 16:422. [PMID: 36329514 PMCID: PMC9632563 DOI: 10.1186/s13256-022-03542-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 07/25/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Recently, an unknown hepatitis outbreak among children has concerned many individuals worldwide. These cases are frequently reported, mainly from Europe and other countries. In this study, we present two similar patients, who, to the best of our knowledge, are the first cases reported in the Middle East (Shiraz, Fars Province, Iran). Unlike in similar cases reported up until 30 April 2022, our patients' hepatitis eventually resulted in aplastic anemia. CASE PRESENTATION In this study, we present cases of two Iranian boys aged 13 and 8 years with hepatitis of unknown origin who developed aplastic anemia in the course of hospitalization. CONCLUSIONS Hepatitis-associated aplastic anemia is a well-known immune-mediated form of aplastic anemia that we detected in our patients and treated with immunosuppressive therapy. One patient established a satisfactory response to the treatment, but unfortunately, the other was declared brain dead.
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Affiliation(s)
- Ali Ghanei-Shahmirzadi
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hamid Reihani
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Abbasi-Kashkooli
- Student Research Committee, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fereshteh Karbasian
- Department of Pediatric Gastroenterology, Shiraz University of Medical Sciences, Shiraz, Iran.
| | | | | | - Maryam Ataollahi
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Seyed Mohsen Dehghani
- Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Bita Geramizadeh
- Shiraz Transplant Research Center (STRC), Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Pathology, Shiraz University of Medical Sciences, Shiraz, Iran
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15
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Hepatitis-associated Aplastic Anemia. J Pediatr Gastroenterol Nutr 2022; 75:553-555. [PMID: 36070526 DOI: 10.1097/mpg.0000000000003603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Hepatitis-associated aplastic anemia (HAAA) accounts for 4% of autoimmune hepatitis in children. An episode of seronegative autoimmune hepatitis is followed a few days or months later by aplastic anemia or full aplasia. This autoimmune disease could be due to a regulation defect in the immune response to a viral trigger, in a genetically predisposed individual. Other causes of hepatitis or aplastic anemia have to be ruled out. Steroids and azathioprine usually control the liver damage but do not prevent the development of aplastic anemia. Aplastic anemia is treated with either hematopoietic stem cell transplantation in patients with a sibling donor or anti-thymocyte globulins and cyclosporine. We propose guidelines to explore and treat this rare disease. We emphasize on the necessary close collaboration between hepatologists and hematologists.
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16
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Thakur W, Anwar N, Samad S, Fatima N, Ahmed R, Tariq F, Ashfaq J, Sharif S, Borhany M. Assessment of Hepatic Profile in Acquired Aplastic Anemia: An Experience From Pakistan. Cureus 2022; 14:e29079. [PMID: 36249635 PMCID: PMC9558489 DOI: 10.7759/cureus.29079] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/12/2022] [Indexed: 12/04/2022] Open
Abstract
Introduction: Aplastic anemia (AA) is characterized by pancytopenia and hypocellular marrow in the absence of an abnormal infiltrate or increase in reticulin fibrosis. The diagnosis of AA is challenging at times due to decreased cellularity and overlapping morphological features with other bone marrow failure syndromes. Hepatitis-associated aplastic anemia (HAAA) is a rare variant in which patients typically present with jaundice and hepatitis followed by pancytopenia almost within 6 months. Post-hepatitis AA accounts for approximately 1-5% of cases, and invariably such cases are negative for the known hepatitis virus as well. There is limited literature available to understand the correlation of AA with hepatitis with none reported at the national level in our region. As AA is relatively more prevalent in Southeast Asia as compared to the western world and hepatitis is a prevalent disease in our population, the main purpose of this study was to assess the hepatic profile and determine the association of hepatitis in AA at the time of diagnosis. Materials and methods: A cross-sectional study was carried out at the National Institute of Blood Disease and Bone Marrow Transplantation, Karachi, from November 2019 to December 2020 after the informed consent from patients. The study included all treatment-naïve patients of acquired AA with no prior history of taking steroids, immunosuppressive treatment, or chemoradiation therapy. Liver function tests, complete blood count, prothrombin time (PT), and activated partial thromboplastin time were performed, along with viral profiles (HAV, Hep B, Hep C, and HIV). SPSS version 23 (IBM Corp., Armonk, NY) was used for statistical analysis. Mean and standard deviations were computed for quantitative variables while percentages and frequencies were reported for qualitative variables. T-test was used to observe the main difference between groups and a p-value <0.05 was considered to be significant. Results: Out of a total of 351 patients, 29 (8.2%) patients with AA tested positive for viral hepatitis. Hepatitis A was the most prevalent hepatitis (4.0%), followed by hepatitis C (3.7%). The comparison of platelet counts in patients with and without hepatitis was reported to be of statistical significance (p-value < 0.05). A significant statistical difference (p-value < 0.0001) was found in platelet count and PT in patients of AA with and without hepatitis. Conclusion: Overall, this study revealed that <10% of patients of AA had a positive screening for hepatitis A, B, and C and low platelet count, and PT was statistically significant when compared between the patients with and without hepatitis. Hepatitis being prevalent in our part of the world might have an important causal association with AA. Patients with AA should be screened for liver functions and viral hepatitis at the time of diagnosis. In addition to hepatitis A, B, and C and HIV, other causes of hepatitis should also be screened such as parvovirus B19, human herpes virus 16, and adenovirus which are not included in routine diagnostic viral testing panel.
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17
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Abbas WAK. Alpha-fetoprotein and high sensitive C-reactive protein levels in Iraqi patients with liver cirrhosis. JOURNAL OF POPULATION THERAPEUTICS AND CLINICAL PHARMACOLOGY = JOURNAL DE LA THERAPEUTIQUE DES POPULATIONS ET DE LA PHARMACOLOGIE CLINIQUE 2022; 29:e11-e16. [PMID: 36196934 DOI: 10.47750/jptcp.2022.905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/09/2022] [Accepted: 06/11/2022] [Indexed: 06/16/2023]
Abstract
BACKGROUND Liver-related death globally is caused mainly by cirrhosis. It is the final grade of extensive liver fibrosis, in which the hepatic architecture is modified. Cirrhosis is a common disease worldwide and can be the end stage for several reasons such as obesity, non-alcoholic fatty liver, alcoholism, viral infection such as viral hepatitis, immune disorders, bile duct obstruction, and metabolic diseases. Alpha-fetoprotein (AFP) is defined as a protein secreted by the germinal yolk sac and liver. AFP level is used as a marker to diagnose inherited disorders and chromosomal anomaly, whereas the high-sensitivity C-reactive protein (hs-CRP) has a separate correlation with NAFLD. Therefore, hs-CRP can be used as a beneficial marker for identifying liver defects. SUBJECTS AND METHODS Thirty participants with liver cirrhosis and 30 healthy participants as control (male and female) were enrolled. The participants from Baghdad, Iraq, were enrolled in this study. Blood and serum samples were obtained for the estimation of hemoglobin, serum AFP, and hs-CRP levels. RESULTS The pooled data of participants showed that hs-CRP and alpha-fetoprotein levels in the participants with cirrhosis were significantly higher than in the control group, P<0.0001. There were no significant differences in the sexes while considering alpha-fetoprotein, whereas hs-CRP levels were higher in males compared with females. CONCLUSION This research shows a significantly high level of hs-CRP and alpha-fetoprotein in patients with liver cirrhosis compared with the control participants. There were non-significant gender differences concerning alpha-fetoprotein with significantly high level of hs-CRP in males compared with females.
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Affiliation(s)
- Wassan Abdul Kareem Abbas
- Department of Clinical Laboratory Sciences, College of Pharmacy, Mustansiriyah University, Baghdad, Iraq;
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18
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Ma X, Zuo Y, Xu Z, Zhang Y, Cheng Y, Han T, Suo P, Sun Y, Tang F, Wang F, Yan C, Chen Y, Wang Y, Zhang X, Liu K, Huang X, Xu L. Comparable clinical outcomes of haploidentical hematopoietic stem cell transplantation in patients with hepatitis-associated aplastic anemia and non-hepatitis-associated aplastic anemia. Ann Hematol 2022; 101:1815-1823. [PMID: 35739427 DOI: 10.1007/s00277-022-04885-w] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 06/12/2022] [Indexed: 11/30/2022]
Abstract
Hepatitis-associated aplastic anemia (HAAA), a rare subtype of aplastic anemia (AA), is defined as bone marrow failure occurring after acute hepatitis. Severe HAAA requires immunosuppressive therapy (IST) or hematopoietic stem cell transplantation (HSCT) as lifesaving treatment. The outcomes of HAAA patients who underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) have not been systematically evaluated. We retrospectively compared the characteristics of 15 patients with HAAA and 60 non-hepatitis-associated aplastic anemia (non-HAAA) patients, all 75 of whom underwent haplo-HSCT in our hospital between January 2006 and October 2021. The median ages of the patients were 18 years old (range, 3-36) for HAAA patients and 13 years (range, 2-45) for non-HAAA patients (p = 0.693). The median time for neutrophil engraftment was 14 days (range, 11-22) in the HAAA group and 12 days (range, 10-21) in the non-HAAA group (p = 0.363). At the time of analysis, 15 HAAA patients and 58 non-HAAA patients were alive, and their median follow-up times were 37 (range, 3-87) months and 31 (range, 2-110) months (p = 0.347), respectively. There were no significant differences in the three-year overall survival (OS) rates (100% vs. 96.7 ± 0.33%, P = 0.638) or liver event-free survival (LEFS) (80.0 ± 0.17% vs. 76.7 ± 0.19%, P = 0.747) between the two groups. Despite the small number of HAAA patients due to the rarity of the disease, these results, such as the similar incidence rates of 3-year OS and fewer liver events than expected, suggest that haplo-HSCT is a feasible treatment for HAAA a when there are no human leukocyte antigen (HLA)-matched donors available and has a low risk of transplant-related mortality and complications.
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Affiliation(s)
- Xiaodi Ma
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Yangyang Zuo
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Zhengli Xu
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Yuanyuan Zhang
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Yifei Cheng
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Tingting Han
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Pan Suo
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Yuqian Sun
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Feifei Tang
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Fengrong Wang
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Chenhua Yan
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Yuhong Chen
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Yu Wang
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Xiaohui Zhang
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Kaiyan Liu
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China
| | - Xiaojun Huang
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China.,Peking-Tsinghua Centre for Life Sciences, Beijing, China
| | - Lanping Xu
- National Clinical Research Centre for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplant, Peking University People's Hospital, Peking University Institute of Hematology, No. 11 Xizhimen South Street, Xicheng District, 100044, Beijing, China.
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19
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Tao X, Chen L, Zhao Y, Liu Y, Shi R, Jiang B, Mi Y, Xu L. A Novel Noninvasive Diagnostic Model of HBV-Related Inflammation in Chronic Hepatitis B Virus Infection Patients With Concurrent Nonalcoholic Fatty Liver Disease. Front Med (Lausanne) 2022; 9:862879. [PMID: 35402467 PMCID: PMC8984271 DOI: 10.3389/fmed.2022.862879] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 02/14/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND AND AIMS Patients with chronic hepatitis B virus infection (CBI) with concurrent nonalcoholic fatty liver disease (NAFLD) is becoming increasingly common in clinical practice, and it is quite important to identify the etiology when hepatitis occurs. A noninvasive diagnostic model was constructed to identify patients who need antihepatitis B virus (HBV) therapies [histologic activity index (HAI) ≥ 4] in patients with CBI with concurrent NAFLD by analyzing clinical routine parameters. APPROACH AND RESULTS In total, 303 out of 502 patients with CBI with concurrent NAFLD proven by liver biopsy from January 2017 to December 2020 in the Tianjin Second People's Hospital were enrolled and they were divided into the HBV-related inflammation (HBV-I) group (HAI ≥ 4,176 cases) and the non-HBV-I group (HAI < 4,127 cases) according to hepatic pathology. The univariate analysis and multivariate logistic regression analysis were performed on the two groups of patients, and then the HBV-I model of patients with CBI with concurrent NAFLD was constructed. The areas under receiver operating characteristic curves (AUROCs) were used to evaluate the parameters of the regression formula. Another 115 patients with CBI with concurrent NAFLD proven by liver biopsy from January 2021 to January 2022 were enrolled as the validation group. There were some statistical differences in demographic data, biochemical indicators, immune function, thyroid function, virology indicator, and blood routine indicators between the two groups (P < 0.05) and liver stiffness measurement (LSM) in the HBV-I group was significantly higher than those in the non-HBV-I group (P < 0.05). While controlled attenuation parameters (CAP) in the HBV-I group were lower than those in the non-HBV-I group (P < 0.05); (2) We developed a novel model by logistic regression analysis: HBV-I = -0.020 × CAP + 0.424 × LSM + 0.376 × lg (HBV DNA) + 0.049 × aspartate aminotransferase (AST) and the accuracy rate was 82.5%. The area under the receiver operating characteristic (AUROC) is 0.907, the cutoff value is 0.671, the sensitivity is 89.30%, the specificity is 77.80%, the positive predictive value is 90.34%, and the negative predictive value is 81.89%; (3) The AUROC of HBV-I in the validation group was 0.871 and the overall accuracy rate is 86.96%. CONCLUSION Our novel model HBV-I [combining CAP, LSM, lg (HBV DNA), and AST] shows promising utility for predicting HBV-I in patients with CBI with concurrent NAFLD with high sensitivity, accuracy, and repeatability, which may contribute to clinical application.
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Affiliation(s)
- Xuemei Tao
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Lin Chen
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Youfei Zhao
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Yonggang Liu
- Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Ruifang Shi
- Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Bei Jiang
- Tianjin Research Institute of Liver Diseases, Tianjin, China
| | - Yuqiang Mi
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
| | - Liang Xu
- Clinical School of the Second People's Hospital, Tianjin Medical University, Tianjin, China
- Department of Hepatology, Tianjin Second People's Hospital, Tianjin, China
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20
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Kakiuchi T, Eguchi K, Koga D, Eguchi H, Nishi M, Sonoda M, Ishimura M, Matsuo M. Changes in bone marrow and peripheral blood lymphocyte subset findings with onset of hepatitis-associated aplastic anemia. Medicine (Baltimore) 2022; 101:e28953. [PMID: 35212305 PMCID: PMC8878616 DOI: 10.1097/md.0000000000028953] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/11/2022] [Indexed: 01/04/2023] Open
Abstract
RATIONALE Hepatitis-associated aplastic anemia (HAAA) is a rare illness that results in bone marrow failure following hepatitis development. The etiological agent remains unknown in most HAAA cases. However, clinical features of the disease and immunotherapy response indicate that immune-mediated factors play a central role in the pathogenesis of HAAA. Activation of cytotoxic T cells and increase in CD8 cells could exert cytotoxic effects on the myelopoietic cells in the bone marrow. PATIENT CONCERNS A 15-month-old boy was brought to our hospital with complaints of generalized petechiae and purpura observed a week prior to hospitalization. His liver was palpated 3 cm below the costal margin, platelet count was 0 × 104/μL, and alanine aminotransferase level was 1346 IU/L. A blood test indicated cytomegalovirus infection, and 3 bone marrow examinations revealed progressive HAAA. As the disease progressed to the 3rd, 6th, and 9th week after onset, CD4+ T cells were markedly decreased, CD8+ T cells were markedly increased, and the CD4/CD8 ratio was significantly decreased. The number of B cells and natural killer cells decreased with time, eventually reaching 0.0%. DIAGNOSIS HAAA. INTERVENTIONS Rabbit antithymocyte globulin and eltrombopag olamine (a thrombopoietin receptor agonist) were administered. OUTCOMES The patient's platelet count returned to normal, and bone marrow transplantation was avoided. The peripheral blood lymphocytes (PBLs) improved as the patient's general condition recovered. LESSONS This case demonstrates that HAAA induced by cytomegalovirus infection features decreasing CD4+ and increasing CD8+ PBLs as the bone marrow hypoplasia progresses. The PBLs return to their normal levels with the recovery from the disease. Our case findings thus support the involvement of immunological abnormality in HAAA.
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Affiliation(s)
- Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Katsuhide Eguchi
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Daisuke Koga
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Hiroi Eguchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Masanori Nishi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Motoshi Sonoda
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Masataka Ishimura
- Department of Pediatrics, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Muneaki Matsuo
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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21
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Li H, Li X, Chen X, Li N. Successful treatment with HLA-matched peripheral hematopoietic stem cell transplantation for very severe hepatitis-associated aplastic anemia complicated with multidrug-resistant bacterial and fungal infections: A case report. Front Pediatr 2022; 10:828918. [PMID: 36389369 PMCID: PMC9659588 DOI: 10.3389/fped.2022.828918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2021] [Accepted: 09/27/2022] [Indexed: 11/13/2022] Open
Abstract
Hepatitis-associated aplastic anemia (HAAA) is a life-threatening hematologic disorder characterized by bone marrow failure. Allogeneic hematopoietic stem cell transplantation (HSCT) is the first-line treatment for HAAA. Severe infection and complications in patients with very severe aplastic anemia are the challenges to the efficacy of HSCT. We report a rare case of successful transplantation with HLA-matched peripheral hematopoietic stem cells for a 15-year-old girl suffering from HAAA with multidrug-resistant bacterial and fungal infections. Through effectively controlling infection and optimal timing of transplantation by adjusting the conditioning regimen, the allo-HSCT was successfully performed for the patient. Updated data of following-up 26 months after transplantation showed that the patient was still in complete remission with a good quality of life. This case provided a reference for treating severely infected patients with HAAA before HSCT.
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Affiliation(s)
- Hua Li
- Hemopoietic Stem Cell Transplantation Center, Fujian Provincial Key Laboratory on Hematology, Clinical Research Center for Hematological Malignancies of Fujian Province, Fujian Institute of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China.,Department of Hematology, The Second Affiliated Hospital of Xiamen Medical College, Xiamen, China
| | - Xiaofan Li
- Hemopoietic Stem Cell Transplantation Center, Fujian Provincial Key Laboratory on Hematology, Clinical Research Center for Hematological Malignancies of Fujian Province, Fujian Institute of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xianling Chen
- Hemopoietic Stem Cell Transplantation Center, Fujian Provincial Key Laboratory on Hematology, Clinical Research Center for Hematological Malignancies of Fujian Province, Fujian Institute of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Nainong Li
- Hemopoietic Stem Cell Transplantation Center, Fujian Provincial Key Laboratory on Hematology, Clinical Research Center for Hematological Malignancies of Fujian Province, Fujian Institute of Hematology, Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, China
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22
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Tüfekçi Ö, Özdemir HH, Malbora B, Özbek NY, Yarali N, Erdem A, Evim M, Baytan B, Güneş AM, Karapinar T, Oymak Y, Töret E, Bör Ö, Yilmaz Ş, Ören H, Özdemir GN, Karapinar DY. Hepatitis-Associated Aplastic Anemia: Etiology, Clinical Characteristics and Outcome. J Pediatr Hematol Oncol 2022; 44:e223-e226. [PMID: 34669357 DOI: 10.1097/mph.0000000000002268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/27/2021] [Indexed: 11/26/2022]
Abstract
Hepatitis-associated aplastic anemia (HAA) is a form of acquired aplastic anemia (AA) in which bone marrow failure develops after an acute attack of hepatitis. Bone marrow failure leading to AA is generally severe in cases of HAA and fatal if left untreated. This retrospective multicenter study investigated clinical and laboratory characteristics, possible causes, treatment, and outcome of HAA in children. Twenty patients from 8 centers were included in the study. Aspartate aminotransferase and alanine aminotransferase were <3 to 5×upper limit of normal (ULN) in 2 patients, <5 to 10×ULN in 2 patients, and >10×ULN in 16 patients. Acute liver failure developed in 5 (29%) patients. Pancytopenia was simultaneously present in 6 of 20 (30%) patients. Eleven of the 20 patients (55%) were alive, in remission and transfusion free. Those who were alive either had undergone hematopoietic stem cell transplantation and/or immunosuppressive treatment, except 1 patient who had received no treatment. Patients with the diagnosis of acute hepatitis should be evaluated and followed up carefully for presence of cytopenia, so that definitive treatment of AA can be initiated in a timely and appropriate manner when needed.
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Affiliation(s)
- Özlem Tüfekçi
- Department of Pediatric Hematology, Dokuz Eylül University Faculty of Medicine
| | - Hamiyet H Özdemir
- Department of Pediatric Hematology, Ege University Faculty of Medicine
| | - Bariş Malbora
- Department of Pediatric Hematology/Oncology, Ankara City Hospital, The University of Health Sciences, Ankara
| | - Namik Y Özbek
- Department of Pediatric Hematology/Oncology, Ankara City Hospital, The University of Health Sciences, Ankara
| | - Neşe Yarali
- Department of Pediatric Hematology/Oncology, Ankara City Hospital, The University of Health Sciences, Ankara
| | - Arzu Erdem
- Department of Pediatric Hematology/Oncology, Ankara City Hospital, The University of Health Sciences, Ankara
| | - Melike Evim
- Department of Pediatric Hematology, Uludağ University Faculty of Medicine, Bursa
| | - Birol Baytan
- Department of Pediatric Hematology, Uludağ University Faculty of Medicine, Bursa
| | - Adalet M Güneş
- Department of Pediatric Hematology, Uludağ University Faculty of Medicine, Bursa
| | - Tuba Karapinar
- Department of Pediatric Hematology/Oncology, İstinye University Faculty of Medicine, İstanbul, Turkey
| | - Yeşim Oymak
- Department of Pediatric Hematology/Oncology, İstinye University Faculty of Medicine, İstanbul, Turkey
| | - Ersin Töret
- Department of Pediatric Hematology, Osmangazi University Faculty of Medicine, Eskişehir
| | - Özcan Bör
- Department of Pediatric Hematology, Osmangazi University Faculty of Medicine, Eskişehir
| | - Şebnem Yilmaz
- Department of Pediatric Hematology, Dokuz Eylül University Faculty of Medicine
| | - Hale Ören
- Department of Pediatric Hematology, Dokuz Eylül University Faculty of Medicine
| | - Gül N Özdemir
- Department of Pediatric Hematology/Oncology, İstinye University Faculty of Medicine, İstanbul, Turkey
| | - Deniz Y Karapinar
- Department of Pediatric Hematology, Ege University Faculty of Medicine
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23
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Shimano KA, Narla A, Rose MJ, Gloude NJ, Allen SW, Bergstrom K, Broglie L, Carella BA, Castillo P, Jong JLO, Dror Y, Geddis AE, Huang JN, Lau BW, McGuinn C, Nakano TA, Overholt K, Rothman JA, Sharathkumar A, Shereck E, Vlachos A, Olson TS, Bertuch AA, Wlodarski MW, Shimamura A, Boklan J. Diagnostic work-up for severe aplastic anemia in children: Consensus of the North American Pediatric Aplastic Anemia Consortium. Am J Hematol 2021; 96:1491-1504. [PMID: 34342889 DOI: 10.1002/ajh.26310] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 07/26/2021] [Accepted: 07/27/2021] [Indexed: 12/19/2022]
Abstract
The North American Pediatric Aplastic Anemia Consortium (NAPAAC) is a group of pediatric hematologist-oncologists, hematopathologists, and bone marrow transplant physicians from 46 institutions in North America with interest and expertise in aplastic anemia, inherited bone marrow failure syndromes, and myelodysplastic syndromes. The NAPAAC Bone Marrow Failure Diagnosis and Care Guidelines Working Group was established with the charge of harmonizing the approach to the diagnostic workup of aplastic anemia in an effort to standardize best practices in the field. This document outlines the rationale for initial evaluations in pediatric patients presenting with signs and symptoms concerning for severe aplastic anemia.
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Affiliation(s)
- Kristin A. Shimano
- Department of Pediatrics University of California San Francisco Benioff Children's Hospital San Francisco California USA
| | - Anupama Narla
- Department of Pediatrics Stanford University School of Medicine Stanford California USA
| | - Melissa J. Rose
- Division of Hematology, Oncology, and Bone Marrow Transplant Nationwide Children's Hospital, The Ohio State University College of Medicine Columbus Ohio USA
| | - Nicholas J. Gloude
- Department of Pediatrics University of California San Diego, Rady Children's Hospital San Diego California USA
| | - Steven W. Allen
- Pediatric Hematology/Oncology University of Pittsburgh School of Medicine, UPMC Children's Hospital of Pittsburgh Pittsburgh Pennsylvania USA
| | - Katie Bergstrom
- Cancer and Blood Disorders Center Seattle Children's Hospital Seattle Washington USA
| | - Larisa Broglie
- Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation Medical College of Wisconsin Milwaukee Wisconsin USA
| | - Beth A. Carella
- Department of Pediatrics Kaiser Permanente Washington District of Columbia USA
| | - Paul Castillo
- Division of Pediatric Hematology Oncology UF Health Shands Children's Hospital Gainesville Florida USA
| | - Jill L. O. Jong
- Section of Hematology‐Oncology, Department of Pediatrics University of Chicago Chicago Illinois USA
| | - Yigal Dror
- Marrow Failure and Myelodysplasia Program, Division of Hematology and Oncology, Department of Paediatrics The Hospital for Sick Children Toronto Ontario Canada
| | - Amy E. Geddis
- Cancer and Blood Disorders Center Seattle Children's Hospital Seattle Washington USA
| | - James N. Huang
- Department of Pediatrics University of California San Francisco Benioff Children's Hospital San Francisco California USA
| | - Bonnie W. Lau
- Pediatric Hematology‐Oncology Dartmouth‐Hitchcock Lebanon New Hampshire USA
| | - Catherine McGuinn
- Department of Pediatrics Weill Cornell Medicine New York New York USA
| | - Taizo A. Nakano
- Center for Cancer and Blood Disorders Children's Hospital Colorado Aurora Colorado USA
| | - Kathleen Overholt
- Pediatric Hematology and Oncology Riley Hospital for Children at Indiana University Indianapolis Indiana USA
| | - Jennifer A. Rothman
- Division of Pediatric Hematology and Oncology Duke University Medical Center Durham North Carolina USA
| | - Anjali Sharathkumar
- Stead Family Department of Pediatrics University of Iowa Carver College of Medicine Iowa City Iowa USA
| | - Evan Shereck
- Department of Pediatrics Oregon Health and Science University Portland Oregon USA
| | - Adrianna Vlachos
- Hematology, Oncology and Cellular Therapy Cohen Children's Medical Center New Hyde Park New York USA
| | - Timothy S. Olson
- Cell Therapy and Transplant Section, Division of Oncology and Bone Marrow Failure, Division of Hematology, Department of Pediatrics Children's Hospital of Philadelphia and University of Pennsylvania Philadelphia Pennsylvania USA
| | | | | | - Akiko Shimamura
- Cancer and Blood Disorders Center Boston Children's Hospital and Dana Farber Cancer Institute Boston Massachusetts USA
| | - Jessica Boklan
- Center for Cancer and Blood Disorders Phoenix Children's Hospital Phoenix Arizona USA
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24
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Jiang X, Hu Y, Qu XP, Xu DW, Jiang H, Li CM, Jiang H, Wang DL, Li G, Zhu XG, Liu B. Prediction of in-hospital recurrence and false-negative results in patients with COVID-19 by red blood cell values on admission. Exp Ther Med 2021; 22:1250. [PMID: 34539846 PMCID: PMC8438694 DOI: 10.3892/etm.2021.10685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/26/2021] [Indexed: 01/08/2023] Open
Abstract
The clinical characteristics and risk factors of patients with coronavirus disease 2019 (COVID-19) with re-positive or false-negative test results have so far remained to be determined. The present study provides a cross-sectional observational study on 134 hospitalized patients selected from Huoshenshan Hospital (Wuhan, China) using cluster sampling. A total of 68 patients had reduced red blood cell (RBC) counts, 55 a decrease in the hemoglobin concentration (HBC) and 73 a decline in hematocrit (HCT). The false-negative rate of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA detection in pharyngeal swab specimens was 18.7%. The absolute lymphocyte count (ALC), RBC, HBC and HCT levels in false-negative patients were significantly higher than those in patients who tested positive for viral nucleic acids. Multivariate logistic regression analysis indicated that RBC [odds ratio (OR)=0.43, 95% CI: 0.18-0.99], HBC (OR=0.97, 95% CI: 0.94-0.99) and ALC (OR=0.43, 95% CI: 0.20-0.91) were the factors influencing the negative testing results for viral nucleic acid. The rate of re-positive patients was 16.4%. The white blood cell, RBC, HBC and HCT values in re-positive patients were lower than those in non-re-positive patients. The median (interquartile range) values for RBC, HBC and HCT of male re-positive patients were 3.95 (3.37, 4.2) x1012/l, 123 (103, 133) g/l and 36.6 (31.1, 39.2)%, respectively, while the RBC, HBC and HCT of female re-positive patients were 3.54 (3.13, 3.74) x1012/l, 115 (102, 118) g/l and 34.2 (28.5, 34.9)%, respectively. It was determined that RBC, HBC and HCT values had moderate accuracy in predicting SARS-CoV-2 recurrence in patients with COVID-19 using receiver operating curve analysis. The present study suggested that RBC may have an important role in the pathogenesis of COVID-19.
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Affiliation(s)
- Xue Jiang
- Third Department of Infectious Diseases, Huoshenshan Hospital, Joint Logistics Support Force of The Chinese People's Liberation Army, Wuhan, Hubei 430101, P.R. China.,Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Yan Hu
- Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China.,Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Xiao-Peng Qu
- Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Dong-Wei Xu
- Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Hong Jiang
- Third Department of Infectious Diseases, Huoshenshan Hospital, Joint Logistics Support Force of The Chinese People's Liberation Army, Wuhan, Hubei 430101, P.R. China.,Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Chun-Mei Li
- Third Department of Infectious Diseases, Huoshenshan Hospital, Joint Logistics Support Force of The Chinese People's Liberation Army, Wuhan, Hubei 430101, P.R. China.,Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Hua Jiang
- Third Department of Infectious Diseases, Huoshenshan Hospital, Joint Logistics Support Force of The Chinese People's Liberation Army, Wuhan, Hubei 430101, P.R. China.,Department of Respiratory Medicine, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Da-Li Wang
- Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Gang Li
- Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
| | - Xin-Gen Zhu
- Department of Neurosurgery, The Second Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330008, P.R. China
| | - Bei Liu
- Third Department of Infectious Diseases, Huoshenshan Hospital, Joint Logistics Support Force of The Chinese People's Liberation Army, Wuhan, Hubei 430101, P.R. China.,Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shanxi 710038, P.R. China
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25
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Groarke EM, Young NS, Calvo KR. Distinguishing constitutional from acquired bone marrow failure in the hematology clinic. Best Pract Res Clin Haematol 2021; 34:101275. [PMID: 34404527 DOI: 10.1016/j.beha.2021.101275] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2021] [Revised: 05/19/2021] [Accepted: 05/22/2021] [Indexed: 12/23/2022]
Abstract
Distinguishing constitutional from immune bone marrow failure (BMF) has important clinical implications. However, the diagnosis is not always straightforward, and immune aplastic anemia, the commonest BMF, is a diagnosis of exclusion. In this review, we discuss a general approach to the evaluation of BMF, focusing on clinical presentations particular to immune and various constitutional disorders as well as the interpretation of bone marrow histology, flow cytometry, and karyotyping. Additionally, we examine the role of specialized testing in both immune and inherited BMF, and discuss genetic testing, both its role in patient evaluation and interpretation of results.
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Affiliation(s)
- Emma M Groarke
- Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Clinical Center, Building 10, 3-E, room 3-5240, 10 Center Drive, Bethesda, MD, 20892, United States.
| | - Neal S Young
- Hematology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Clinical Center, Building 10, 3-E, room 3-5240, 10 Center Drive, Bethesda, MD, 20892, United States.
| | - Katherine R Calvo
- Hematology Section, Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Clinical Center, Building 10, Department of Laboratory Medicine, 10 Center Drive, Bethesda, MD, 20892, United States.
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26
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Chapin CA, Taylor SA, Malladi P, Neighbors K, Melin-Aldana H, Kreiger PA, Bowsher N, Schipma MJ, Loomes KM, Behrens EM, Alonso EM. Transcriptional Analysis of Liver Tissue Identifies Distinct Phenotypes of Indeterminate Pediatric Acute Liver Failure. Hepatol Commun 2021; 5:1373-1384. [PMID: 34430782 PMCID: PMC8369940 DOI: 10.1002/hep4.1726] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Accepted: 03/01/2021] [Indexed: 02/04/2023] Open
Abstract
Many patients with indeterminate pediatric acute liver failure (PALF) have evidence of T-cell driven immune injury; however, the precise inflammatory pathways are not well defined. We have characterized the hepatic cytokine and transcriptional signatures of patients with PALF. A retrospective review was performed on 22 children presenting with indeterminate (IND-PALF; n = 17) or other known diagnoses (DX-PALF; n = 6) with available archived liver tissue. Specimens were stained for clusters of differentiation 8 (CD8) T cells and scored as dense, moderate, or minimal. Measurement of immune analytes and RNA sequencing (RNA-seq) was performed on whole-liver tissue. Immune analyte data were analyzed by principal component analysis, and RNA-seq was analyzed by unsupervised hierarchical clustering, differential gene expression, and gene-set enrichment analysis. Most patients with IND-PALF (94%) had dense/moderate CD8 staining and were characterized by Th1 immune analytes including tumor necrosis factor α, interferon γ (IFN-γ), interleukin (IL) 1β, IL-12, C-X-C motif chemokine ligand (CXCL) 9, and CXCL12. Transcriptional analyses identified two transcriptional PALF phenotypes. Most patients in group 1 (91%) had IND-PALF and dense/moderate CD8 staining. This group was characterized by increased expression of genes and cell subset-specific signatures related to innate inflammation, T-cell activation, and antigen stimulation. Group 1 expressed significantly higher levels of gene signatures for regulatory T cells, macrophages, Th1 cells, T effector memory cells, cytotoxic T cells, and activated dendritic cells (adjusted P < 0.05). In contrast, patients in group 2 exhibited increased expression for genes involved in metabolic processes. Conclusion: Patients with IND-PALF have evidence of a Th1-mediated inflammatory response driven by IFN-γ. Transcriptional analyses suggest that a complex immune network may regulate an immune-driven PALF phenotype with less evidence of metabolic processes. These findings provide insight into mechanisms of hepatic injury in PALF, areas for future research, and potential therapeutic targets.
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Affiliation(s)
- Catherine A Chapin
- Department of PediatricsNorthwestern UniversityFeinberg School of MedicineAnn & Robert H. Lurie Children's Hospital of ChicagoChicagoILUSA
| | - Sarah A Taylor
- Department of PediatricsNorthwestern UniversityFeinberg School of MedicineAnn & Robert H. Lurie Children's Hospital of ChicagoChicagoILUSA
| | - Padmini Malladi
- Department of PediatricsNorthwestern UniversityFeinberg School of MedicineAnn & Robert H. Lurie Children's Hospital of ChicagoChicagoILUSA
| | - Katie Neighbors
- Department of PediatricsNorthwestern UniversityFeinberg School of MedicineAnn & Robert H. Lurie Children's Hospital of ChicagoChicagoILUSA
| | - Hector Melin-Aldana
- Department of Pathology and Laboratory MedicineNorthwestern UniversityFeinberg School of MedicineAnn & Robert H. Lurie Children's Hospital of ChicagoChicagoILUSA
| | - Portia A Kreiger
- Department of Pathology and Laboratory MedicineUniversity of PennsylvaniaPerelman School of MedicineThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA
| | - Nina Bowsher
- Preventative MedicineBiostatistics Collaboration CenterNorthwestern UniversityFeinberg School of MedicineChicagoILUSA
| | - Matthew J Schipma
- Next Generation Sequencing CoreNorthwestern UniversityFeinberg School of MedicineChicagoILUSA
| | - Kathleen M Loomes
- Department of PediatricsUniversity of PennsylvaniaPerelman School of MedicineThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA
| | - Edward M Behrens
- Department of PediatricsUniversity of PennsylvaniaPerelman School of MedicineThe Children's Hospital of PhiladelphiaPhiladelphiaPAUSA
| | - Estella M Alonso
- Department of PediatricsNorthwestern UniversityFeinberg School of MedicineAnn & Robert H. Lurie Children's Hospital of ChicagoChicagoILUSA
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Atypical Outcomes for Hepatitis-associated Acquired Aplastic Anemia: 2 Case Studies and Review of the Literature. J Pediatr Hematol Oncol 2021; 43:195-199. [PMID: 32815884 DOI: 10.1097/mph.0000000000001916] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 07/09/2020] [Indexed: 11/26/2022]
Abstract
There is little data specifically dedicated to the long-term outcomes of the hepatitis-associated variant of aplastic anemia (HAAA). A majority of patients with nonsevere (moderate) aplastic anemia progress to severe aplastic anemia, and severe aplastic anemia typically results in death if left untreated. We present 2 unique cases of HAAA that contribute to our knowledge of the natural history of this disease variant. One patient had moderate HAAA that never progressed to severe disease. The second patient had severe HAAA that spontaneously resolved without treatment. The rare possibility of moderate HAAA failing to progress to fulfill severe criteria, or of severe HAAA spontaneously improving, may complicate early treatment decisions for some patients.
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Fang L, Meikuang L, Ye G, Xiaojuan C, Wenyu Y, Min R, Lixian C, Weiqiang W, Zhibo H, Zhongchao H, Xiaofan Z. Successful Treatment of a 19-Month-Old Boy with Hepatitis Associated Aplastic Anemia by Infusion of Umbilical Cord-Derived Mesenchymal Stromal Cells: A Case Report. Cell Transplant 2021; 30:963689720977144. [PMID: 33525921 PMCID: PMC7863554 DOI: 10.1177/0963689720977144] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Here we presented a case of a 19-month-old boy who developed severe aplastic anemia postacute hepatitis. He was treated successfully with the umbilical cord-derived mesenchymal stromal cells (UC-MSCs) infusion and cyclosporine A (CsA). The boy achieved both hematopoietic recovery and normal lymphocyte proportion. So far, his condition still remains stable. To our knowledge, there is a rare previous report on the utility of MSCs infusion for the treatment of hepatitis-associated aplastic anemia (HAAA). Considering the efficacy, safety, and strong operability, particularly for pediatric patient, the infusion of UC-MSCs combined with CsA could be an effective alternative for the treatment of HAAA.
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Affiliation(s)
- Liu Fang
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
| | - Lim Meikuang
- National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, China
| | - Guo Ye
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
| | - Chen Xiaojuan
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
| | - Yang Wenyu
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
| | - Ruan Min
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
| | - Chang Lixian
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
| | - Wang Weiqiang
- National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, China
| | - Han Zhibo
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.,National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, China
| | - Han Zhongchao
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.,National Engineering Research Center of Cell Products, Tianjin AmCellGene Engineering Co., Ltd, Tianjin, China
| | - Zhu Xiaofan
- Institute of Hematology and Blood Diseases Hospital, 12501Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China
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Kemme S, Stahl M, Brigham D, Lovell MA, Nakano T, Feldman AG, Mack C. Outcomes of Severe Seronegative Hepatitis-associated Aplastic Anemia: A Pediatric Case Series. J Pediatr Gastroenterol Nutr 2021; 72:194-201. [PMID: 32925550 PMCID: PMC7856235 DOI: 10.1097/mpg.0000000000002940] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Hepatitis-associated aplastic anemia (HAAA) is a potentially life-threatening diagnosis without clear treatment guidelines. The goal of the study was to characterize the presentation, evaluation, histopathology, and outcomes of therapy in children with HAAA to guide future research and to develop standardized care guidelines for this rare disease. METHODS Retrospective chart review of 4 patients with HAAA who presented to Children's Hospital Colorado between 2016 and 2019 was conducted. Patient presentation, evaluation, bone marrow and liver pathology, interventions, and clinical course were collected. Immunohistochemistry of liver biopsies was performed. RESULTS We treated 4 patients with HAAA without liver failure. All had evidence of systemic hyperinflammation and CD8+ T cell predominant liver tissue infiltration. One had a genetic mutation predisposing him to immune-mediated disease, but all other genetic testing was negative. In 3 of the 4 patients, hepatitis was poorly responsive to standard therapy with steroids, azathioprine, or tacrolimus; however, sustained biochemical remission of hepatitis was induced after more aggressive immunosuppressive therapies including Anti-Thymocyte Globulin (ATG) at standard immunosuppressive therapy (IST) dosing for severe Aplastic Anemia (sAA). Two patients underwent hematopoietic stem cell transplant (HSCT); 1 as first line therapy and 1 for refractory sAA. CONCLUSIONS We found that ATG-based IST induced remission of hepatitis in patients with steroid-refractory HAAA. This is also an appropriate initial treatment for severe Aplastic Anemia, though may not prevent the need for HSCT. We propose that equine ATG based IST at standard dosing regimen for sAA is a therapy that in select cases can be considered early on in the treatment course and could lead to a sustained remission of both hepatitis and sAA. This should be considered in collaboration with a pediatric hematologist.
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Affiliation(s)
- Sarah Kemme
- Section of Gastroenterology, Hepatology and Nutrition, and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine
| | - Marisa Stahl
- Section of Gastroenterology, Hepatology and Nutrition, and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine
| | - Dania Brigham
- Section of Gastroenterology, Hepatology and Nutrition, and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine
| | - Mark A Lovell
- Section of Pathology and Lab Services, Children's Hospital Colorado, University of Colorado Denver School of Medicine
| | - Taizo Nakano
- Center for Cancer and Blood Disorders, Children's Hospital Colorado, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Amy G Feldman
- Section of Gastroenterology, Hepatology and Nutrition, and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine
| | - Cara Mack
- Section of Gastroenterology, Hepatology and Nutrition, and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine
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30
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Chapin CA, Melin-Aldana H, Kreiger PA, Burn T, Neighbors K, Taylor SA, Ostilla L, Wechsler JB, Horslen SP, Leonis MA, Loomes KM, Behrens EM, Squires RH, Alonso EM. Activated CD8 T-cell Hepatitis in Children With Indeterminate Acute Liver Failure: Results From a Multicenter Cohort. J Pediatr Gastroenterol Nutr 2020; 71:713-719. [PMID: 32796431 DOI: 10.1097/mpg.0000000000002893] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
OBJECTIVES In many pediatric acute liver failure (PALF) cases, a diagnosis is not identified, and the etiology is indeterminate (IND-PALF). Our pilot study found dense CD8 T-cell infiltrates and increased T-cell clonality in liver specimens from IND-PALF patients. We aimed to validate these findings in a multicenter cohort with investigators blinded to diagnosis. METHODS PALF Study Group registry subjects with IND-PALF (n = 37) and known diagnoses (DX-PALF) (n = 18), ages 1 to 17 years, with archived liver tissue were included. Liver tissue slides were stained for T cells (CD8 and CD4), B cells (CD20), macrophages (CD163), perforin, and tissue resident-memory T cells (Trm, CD103), and scored as minimal, moderate, or dense. Lymphocytes were isolated from frozen liver tissue for T-cell receptor beta (TCRβ) sequencing. RESULTS Dense hepatic CD8 staining was found in significantly more IND-PALF (n = 29, 78%) compared with DX-PALF subjects (n = 5, 28%) (P = 0.001). IND-PALF subjects were more likely to have dense or moderate perforin (88% vs 50%, P = 0.03) and CD103 (82% vs 40%, P = 0.02) staining compared with DX-PALF subjects. TCRβ sequencing of 15 IND-PALF cases demonstrated increased clonal overlap compared with 6 DX-PALF cases (P = 0.002). CONCLUSIONS Dense infiltration of effector Trm CD8 T cells characterizes liver tissue from IND-PALF subjects. Increased clonality suggests the T-cell expansion is antigen(s)-driven as opposed to a nonspecific inflammatory response. These findings support CD8 staining as a new biomarker of the activated CD8 T-cell PALF phenotype. Future studies are needed to characterize potential antigens, host risk factors, and inflammatory pathways with the goal of developing targeted therapies.
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Affiliation(s)
| | - Hector Melin-Aldana
- Department of Pathology and Laboratory Medicine, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago IL
| | - Portia A Kreiger
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - Thomas Burn
- Seattle Children's Hospital, Department of Pediatrics at the University of Washington School of Medicine, Seattle, WA
| | | | | | | | | | - Simon P Horslen
- Seattle Children's Hospital, Department of Pediatrics at the University of Washington School of Medicine, Seattle, WA
| | - Mike A Leonis
- Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL
| | - Kathleen M Loomes
- Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia
| | - Edward M Behrens
- Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia
| | - Robert H Squires
- Division of Gastroenterology, Hepatology & Nutrition, Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA
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31
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Alshaibani A, Dufour C, Risitano A, de Latour R, Aljurf M. Hepatitis-associated aplastic anemia. Hematol Oncol Stem Cell Ther 2020; 15:8-12. [PMID: 33197413 DOI: 10.1016/j.hemonc.2020.10.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Accepted: 10/24/2020] [Indexed: 02/08/2023] Open
Abstract
Hepatitis-associated aplastic anemia (HAAA) is a rare illness, characterized by onset of pancytopenia with a hypoplastic bone marrow that traditionally occurs within 6 months of an increase in serum aminotransferases. HAAA is observed in 1% to 5% of all newly diagnosed cases of acquired aplastic anemia. Several hepatitis viruses have been linked to the disease, but in many cases no specific virus is detected. The exact pathophysiology is unknown; however, immune destruction of hematopoietic stem cells is believed to be the underlying mechanism. HAAA is a potentially lethal disease if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine and allogeneic hematopoietic stem cell transplantation.
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Affiliation(s)
- Alfadel Alshaibani
- King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
| | - Carlo Dufour
- Hematology-Oncology-HSCT Pole, G.Gaslini IRCCS Children Hospital, Genova, Italy.
| | - Antonio Risitano
- Department of Clinical Medicine and Surgery, Bone Marrow Transplant Center, Federico II University of Naples, Naples, Italy.
| | - Regis de Latour
- Saint Louis Hospital, Paris Diderot University, Paris, France.
| | - Mahmoud Aljurf
- King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
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32
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Salem JB, Khammaily M, Dahi S, Mouzari Y, El Asri F, Reda K, Oubaaz A. [A rare cause of bilateral macular hemorrhages]. J Fr Ophtalmol 2020; 44:135-137. [PMID: 32950288 DOI: 10.1016/j.jfo.2020.01.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Accepted: 01/21/2020] [Indexed: 11/25/2022]
Affiliation(s)
- J B Salem
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc.
| | - M Khammaily
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc
| | - S Dahi
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc
| | - Y Mouzari
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc
| | - F El Asri
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc
| | - K Reda
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc
| | - A Oubaaz
- Departement of Ophthalmology, Med V Military Hospital of Rabat, Rabat, Maroc
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33
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Ali N, Butt A, Altaf B, Adil SN, Shaikh MU. Transplant in Aplastic Anemia Using Combined Granulocyte Colony-Stimulating Factor Primed Blood and Bone Marrow Stem Cells: A Retrospective Analysis. Transplant Proc 2020; 53:386-390. [PMID: 32773285 DOI: 10.1016/j.transproceed.2020.06.035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 06/05/2020] [Accepted: 06/29/2020] [Indexed: 10/23/2022]
Abstract
INTRODUCTION Aplastic anemia (AA) is characterized by diminished hematopoietic precursors in the bone marrow, most often due to injury to the pluripotent stem cell. In Pakistan, AA is not uncommon, and allogeneic hematopoietic stem cell transplant remains the only curative option for these patients. OBJECTIVE The objective of this study was to determine the transplant outcome of combined granulocyte colony-stimulating factor (G-CSF) primed blood and bone marrow grafts in adult and pediatric patients with AA. METHODS We retrospectively collected the data of all transplant procedures performed from 2004 to 2019 at Aga Khan University in Karachi, Pakistan. Variables analyzed included age, sex, type of stem cells used, conditioning regimens, and overall survival for patients undergoing transplant in AA. RESULTS A total of 351 transplants were performed during the study period. Out of these, 239 were allogeneic transplants, whereas 112 were autologous procedures. We performed 70 transplants for AA during the study period, of which 52 were male patients and 18 were female patients. The median age ± standard deviation (SD) was 17.5 ± 9.4 years (range, 2-43 years). Cyclophosphamide/antithymocyte globulin (ATG) was used as a conditioning regimen in 65 patients, while ATG/cyclophosphamide/fludarabine was used in 5 patients. In 60 patients, a combination of G-CSF primed blood and bone marrow stem cells were used. The mean CD34 count was 5.2 × 106/kg. Graft-vs-host disease (GVHD) prophylaxis was done with cyclosporine and methotrexate. All patients received standard infection prophylaxis. Engraftment was achieved in 86% of patients. The median day of myeloid engraftment was 15 (range, 10-22 days). Chronic GVHD was present in 3 patients while 4 had acute GVHD. The overall survival was 71.2% (median duration of 80 months). The main cause of mortality was gram-negative sepsis. CONCLUSION A combination of blood and bone marrow stem cells results in early engraftment with decreased frequency of GVHD in AA. The overall survival was comparable to international literature.
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Affiliation(s)
- Natasha Ali
- Department of Pathology & Laboratory Medicine/Oncology, Aga Khan University, Karachi, Pakistan.
| | | | - Bakhtawer Altaf
- Department of Oncology, Aga Khan University, Karachi, Pakistan
| | - Salman Naseem Adil
- Department of Pathology & Laboratory Medicine/Oncology, Aga Khan University, Karachi, Pakistan
| | - Mohammad Usman Shaikh
- Department of Pathology & Laboratory Medicine/Oncology, Aga Khan University, Karachi, Pakistan
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34
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Altay D, Yılmaz E, Özcan A, Karakükçü M, Ünal E, Arslan D. Hepatitis-associated aplastic anemia in pediatric patients: single center experience. Transfus Apher Sci 2020; 59:102900. [PMID: 32773318 DOI: 10.1016/j.transci.2020.102900] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Accepted: 07/22/2020] [Indexed: 11/17/2022]
Abstract
INTRODUCTION Hepatitis-associated aplastic anemia is a rare type of acquired aplastic anemia that occurs after hepatitis. This study investigated cases with hepatitis-associated aplastic anemia. METHODS The files of patients with hepatitis-associated aplastic anemia who were followed up in our hospital between 2011-2019 were reviewed retrospectively. RESULTS A total of 15 patients with hepatitis-associated aplastic anemia (10 males, 5 girls; mean age 10.26 ± 3.61 years) were analyzed. The mean duration between hepatitis and aplastic anemia was 5.06 ± 4.19 months. The majority of patients had mild hepatitis. The causes of hepatitis were detected only in six patients: three had hepatitis B, one had hepatitis A, one had autoimmune hepatitis and, one had a hydatid cyst. The cause of hepatitis was not found in nine patients. Only one patient with hepatitis-associated aplastic anemia developed spontaneous remission, and the others required immunosuppressive therapy and/or hematopoietic stem cell transplantation. Only one patient died because of sepsis. The other patients are still under follow-up and treatment. CONCLUSION Patients with hepatitis-associated aplastic anemia, mostly of unknown cause, can be successfully treated with immunosuppressive therapy and/or hematopoietic stem cell transplantation.
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Affiliation(s)
- Derya Altay
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Erciyes University, Faculty of Medicine, Kayseri, Turkey.
| | - Ebru Yılmaz
- Department of Pediatric Hematology and Oncology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Alper Özcan
- Department of Pediatric Hematology and Oncology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Musa Karakükçü
- Department of Pediatric Hematology and Oncology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Ekrem Ünal
- Department of Pediatric Hematology and Oncology, Erciyes University, Faculty of Medicine, Kayseri, Turkey
| | - Duran Arslan
- Department of Pediatric Gastroenterology, Hepatology and Nutrition, Erciyes University, Faculty of Medicine, Kayseri, Turkey
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Božić Ozretić D, Piplović Vuković T, Vuković J, Madunić S, Podrug K, Puljiz Ž. Fatal Hepatitis-Associated Aplastic Anemia in a Young Male. Case Rep Gastroenterol 2020; 14:383-390. [PMID: 32884515 PMCID: PMC7443668 DOI: 10.1159/000508438] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 05/01/2020] [Indexed: 11/19/2022] Open
Abstract
Hepatitis-associated aplastic anemia is a rare syndrome in which bone marrow failure occurs within weeks to 1 year after attack of acute hepatitis. Studies suggest that cytotoxic T lymphocytes play a central role in bone marrow destruction, but the exact etiology remains unknown. Bone marrow transplantation or immunosuppressive therapy are primary curative options. We present a case of a young male who was admitted to the Department of Gastroenterology and Hepatology for acute hepatitis of an unknown cause. Liver biopsy revealed extensive inflammatory process with hepatocyte necrosis. Forty days later, new onset pancytopenia was identified. Bone marrow biopsy showed severe hypocellularity, and he was diagnosed with severe hepatitis-associated aplastic anemia. Treatment with cyclosporine was initiated, but with inadequate response, and pretransplant evaluation was started. Due to severe neutropenia, following alveotomy procedure, the patient developed deep neck infection with consequent airway obstruction. Despite urgent treatment, his condition deteriorated to sepsis with lethal outcome.
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Affiliation(s)
- Dorotea Božić Ozretić
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split, Croatia
| | - Tonka Piplović Vuković
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split, Croatia
| | - Jonatan Vuković
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split, Croatia.,University of Split, School of Medicine, Split, Croatia
| | - Sanja Madunić
- Department of Haematology, University Hospital of Split, Split, Croatia
| | - Kristian Podrug
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split, Croatia
| | - Željko Puljiz
- Department of Gastroenterology and Hepatology, University Hospital of Split, Split, Croatia.,University of Split, School of Medicine, Split, Croatia
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36
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Singh S, Manrai M, V.S P, Kumar D, Srivastava S, Pathak B. Association of liver cirrhosis severity with anemia: does it matter? Ann Gastroenterol 2020; 33:272-276. [PMID: 32382230 PMCID: PMC7196620 DOI: 10.20524/aog.2020.0478] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/09/2020] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND The etiology of anemia in liver disease is diverse and often multifactorial. Anemia is more severe in advanced stages of liver cirrhosis and can be a predictor of the severity of liver disease. METHODS In this cross-sectional observational study, we included 181 cirrhotic patients with anemia owing to liver cirrhosis and its complications. The population was divided into 2 groups based on the model for end-stage liver disease (MELD) score and the severity of anemia was assessed in the 2 groups. Similarly, hemoglobin levels were assessed in 3 groups based on the Child-Turcotte-Pugh (CTP) classification. RESULTS There was a statistically significant correlation between CTP class and hemoglobin (P<0.001), with the lowest hemoglobin levels in CTP C patients. The correlation coefficient between hemoglobin and MELD score was -0.671 and was statistically significant, establishing that hemoglobin levels decrease with increasing severity of liver cirrhosis. Of 58 patients with macrocytosis, 45 (77.6%) had a MELD score of >12, whereas only 13 patients (22.4%) had a MELD score of <12. This difference was statistically significant (P<0.0001). CONCLUSIONS This study shows that hemoglobin levels decrease with increasing severity of liver disease; thus, this measure can be used in the initial assessment of patients to give a picture of the severity of the disease. A larger prospective trial is needed to establish the use of hemoglobin levels for assessing severity and predicting mortality in patients with liver cirrhosis.
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Affiliation(s)
- Sonal Singh
- Department of Internal Medicine, Military Hospital Dehradun (Sonal Singh)
| | - Manish Manrai
- Department of Internal Medicine, Armed Forces Medical College, Pune (Manish Manrai, Parvathi V.S., Basant Pathak)
| | - Parvathi V.S
- Department of Internal Medicine, Armed Forces Medical College, Pune (Manish Manrai, Parvathi V.S., Basant Pathak)
| | - Dharmendra Kumar
- Department of Internal Medicine, Command Hospital, Pune (Dharmendra Kumar, Sharad Srivastava)
| | - Sharad Srivastava
- Department of Internal Medicine, Command Hospital, Pune (Dharmendra Kumar, Sharad Srivastava)
| | - Basant Pathak
- Department of Internal Medicine, Armed Forces Medical College, Pune (Manish Manrai, Parvathi V.S., Basant Pathak)
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Sawada K, Takai A, Yamada T, Araki O, Yamauchi Y, Eso Y, Takahashi K, Shindo T, Sakurai T, Ueda Y, Seno H. Hepatitis-associated Aplastic Anemia with Rapid Progression of Liver Fibrosis Due to Repeated Hepatitis. Intern Med 2020; 59:1035-1040. [PMID: 31875639 PMCID: PMC7205540 DOI: 10.2169/internalmedicine.4072-19] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
Hepatitis-associated aplastic anemia (HAAA) is a variant of acquired aplastic anemia and characterized by bone marrow failure that follows the development of acute hepatitis. We herein report a rare case of HAAA with rapid progression of liver fibrosis due to repeated hepatitis. A pathological examination of liver specimens revealed liver fibrosis progression over a short period. Immunosuppressive therapy with cyclosporine effectively cured both the pancytopenia and hepatitis. Our case suggests that the pathological examination of the liver tissue is useful for determining a treatment plan and that immunosuppressive therapy is a promising treatment for both aplastic anemia and persistent hepatitis.
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Affiliation(s)
- Kenji Sawada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Atsushi Takai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Tomoyo Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Osamu Araki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Yuki Yamauchi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Yuji Eso
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Ken Takahashi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Takero Shindo
- Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Japan
| | - Takaki Sakurai
- Department of Diagnostic Pathology, Graduate School of Medicine, Kyoto University, Japan
| | - Yoshihide Ueda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
| | - Hiroshi Seno
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Japan
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38
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Delehaye F, Habes D, Dourthe ME, Bertrand Y, Michel G, Gaudichon J, Debray D, Nelken B, Pasquet M, Blanche S, Leblanc T. Management of childhood aplastic anemia following liver transplantation for nonviral hepatitis: A French survey. Pediatr Blood Cancer 2020; 67:e28177. [PMID: 31925926 DOI: 10.1002/pbc.28177] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 12/18/2019] [Accepted: 12/21/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Hepatitis-associated aplastic anemia (AA) is a rare syndrome combining acute hepatitis of variable severity and AA. Hepatitis may be severe enough to require urgent liver transplantation (LT). Herein, we describe clinical presentation and management of a cohort of pediatric patients diagnosed with AA after undergoing LT for nonviral hepatitis. METHODS To describe this rare clinical situation, we performed a national survey and identified nine children treated for AA following LT during the last 10 years in France. RESULTS All patients were treated first for hepatic failure with urgent LT. AA was diagnosed with a median delay of 34 days [21-200] from the diagnosis of hepatitis. Seven children were treated with antithymocyte globulin/cyclosporine, one with CSA alone and one received bone marrow transplantation. At the last visit (median follow-up: 4 years), outcomes were excellent: all patients were alive and in hematological remission (complete remission: 7; partial remission: 2). Immunosuppressive therapy was pursued in all patients due to the liver transplant. No unusual toxicities were reported. CONCLUSION AA after LT is considered a therapeutic challenge. Nevertheless, hematological outcome is good using a standard immunosuppressive approach.
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Affiliation(s)
- Fanny Delehaye
- Department of Pediatric Hematology and Oncology, University Hospital of Caen, Caen, France
| | - Dalila Habes
- Department of Pediatric Hepatology, AP-HP, Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France
| | - Marie-Emilie Dourthe
- Department of Pediatric Hematology and Immunology, AP-HP, Robert-Debré Hospital, Paris, France
| | - Yves Bertrand
- Institute of Pediatric Hematology and Oncology, Hospices Civils de Lyon, University Claude Bernard Lyon 1, Lyon, France
| | - Gerard Michel
- Department of Pediatric Hematology and Oncology and Research Unit EA 3279, Timone Enfants Hospital and Aix-Marseille University, Marseille, France
| | - Jérémie Gaudichon
- Department of Pediatric Hematology and Oncology, University Hospital of Caen, Caen, France
| | - Dominique Debray
- Unit of Pediatric Hepatology, Reference Center for Rare Pediatric Liver Diseases, Necker-Enfants-Malades University Hospital, Paris, France.,Department of medicine, University of Paris-Descartes, Sorbonne Paris-Cité, Paris, France
| | - Brigitte Nelken
- Department of Pediatric Hematology-Oncology, Jeanne de Flandre Hospital, CHRU, Lille, France
| | - Marlène Pasquet
- Department of Pediatric Hematology and Oncology, University hospital of Toulouse, Toulouse, France
| | - Stéphane Blanche
- Department of Pediatric Hematology, Immunology and Rheumatology, AP-HP, Necker Enfants-Malades Hospital, Paris, France
| | - Thierry Leblanc
- Department of Pediatric Hematology and Immunology, AP-HP, Robert-Debré Hospital, Paris, France
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39
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Bastola S, Kc O, Khanal S, Halalau A. Hepatitis-associated aplastic anemia from workout supplement: Rare but potentially fatal entity. SAGE Open Med Case Rep 2020; 8:2050313X20901937. [PMID: 32030129 PMCID: PMC6977214 DOI: 10.1177/2050313x20901937] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 12/31/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatitis-associated aplastic anemia (HAAA) is a rare clinical syndrome characterized by bone marrow failure 1–3 months after development of hepatitis. Untreated, hepatitis-associated aplastic anemia has poor outcome and the mainstay of treatment remains either bone marrow transplant or immunosuppressive therapy. A previously healthy 21-year-old man presented with a 1-week history of right upper quadrant pain and jaundice. Admission labs revealed mixed hyperbilirubinemia and elevated transaminases ranging in 2000s IU/dl. Extensive workup for etiologies of acute hepatitis including viruses, autoimmune, toxins etc. were negative. He admitted to taking “Dust V2,” a workout supplement, for 4 months prior to the presentation. His liver function tests started to improve after conservative treatment. Two months after his discharge, he was found to have severe pancytopenia on routine labs. Bone marrow biopsy revealed hypocellular marrow consistent with aplastic anemia. Extensive workup for etiologies of aplastic anemia were negative. On literature review, none of the components of the supplement were found to cause aplastic anemia. A diagnosis of hepatitis-associated aplastic anemia was made as there was a lag time before development of anemia. His counts failed to improve despite treatment with filgrastim and he was referred for hematopoietic cell transplant.
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Affiliation(s)
- Sanjog Bastola
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA.,Oakland University William Beaumont School of Medicine, Rochester, MI, USA
| | - Ojbindra Kc
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA.,Oakland University William Beaumont School of Medicine, Rochester, MI, USA
| | - Sumesh Khanal
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA
| | - Alexandra Halalau
- Department of Internal Medicine, William Beaumont Hospital, Royal Oak, MI, USA.,Oakland University William Beaumont School of Medicine, Rochester, MI, USA
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40
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Scheiner B, Semmler G, Maurer F, Schwabl P, Bucsics TA, Paternostro R, Bauer D, Simbrunner B, Trauner M, Mandorfer M, Reiberger T. Prevalence of and risk factors for anaemia in patients with advanced chronic liver disease. Liver Int 2020; 40:194-204. [PMID: 31444993 PMCID: PMC6973120 DOI: 10.1111/liv.14229] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 07/19/2019] [Accepted: 08/10/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND Anaemia is common in advanced chronic liver disease (ACLD) as a result of various risk factors. AIMS & METHODS We evaluated the prevalence and severity of anaemia as well as the impact of anaemia on clinical outcomes in consecutive patients with ACLD and portal hypertension. RESULTS Among 494 patients, 324 (66%) patients had anaemia. Anaemic patients showed higher MELD (12 ± 4 vs 9 ± 3; P < .001), lower albumin (34 ± 6 vs 39 ± 5 g/dL; P < .001) and more often Child-Pugh B/C stage (56% vs 17%; P < .001). The prevalence of moderate-severe anaemia (haemoglobin <10 g/dL) increased with the degree of portal hypertension (HVPG: 6-9 mm Hg: 22% vs HVPG: 10-19 mm Hg: 24% vs HVPG ≥ 20 mm Hg: 36%; P = .031). The most common aetiologies of anaemia were gastrointestinal bleeding (25%) and iron deficiency (9%), while reason for anaemia remained unclear in 53% of cases. Male gender (odds ratio [OR]: 1.94 [95% CI: 1.09-3.47]; P = .025), MELD (OR: 1.20 [95% CI: 1.09-1.32]; P < .001), hepatic decompensation (OR: 4.40 [95% CI: 2.48-7.82]; P < .001) and HVPG (OR per mm Hg: 1.07 [95% CI: 1.02-1.13]; P = .004) were independent risk factors for anaemia. Anaemia was associated with hepatic decompensation (1 year: 25.1% vs 8.1%; 5 years: 60.3% vs 32.9%; P < .0001), hospitalization (73% vs 57%; P < .001) and a higher incidence rate of acute-on-chronic liver failure (0.05 [95% CI: 0.04-0.07] vs 0.03 [95% CI: 0.01-0.04]). Anaemic patients had worse overall survival (1 year: 87.1% vs 93.7%, 5 year survival: 50.5% vs 68.6%; P < .0001) and increased liver-related mortality (1 year mortality: 9.7% vs 5.7%, 5 year mortality: 38.0% vs 26.9%; P = .003). CONCLUSION Two-thirds of patients with ACLD suffer from anaemia. The degree of hepatic dysfunction and of portal hypertension correlate with severity of anaemia. Anaemia is associated with decompensation, ACLF and increased mortality in patients with ACLD.
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Affiliation(s)
- Bernhard Scheiner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Georg Semmler
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Florian Maurer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Philipp Schwabl
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Theresa A. Bucsics
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Rafael Paternostro
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - David Bauer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Benedikt Simbrunner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Michael Trauner
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria
| | - Mattias Mandorfer
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
| | - Thomas Reiberger
- Division of Gastroenterology and HepatologyDepartment of Internal Medicine IIIMedical University of ViennaViennaAustria,Vienna Hepatic Hemodynamic LaboratoryMedical University of ViennaViennaAustria
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41
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Chapin CA, Alonso EM. Reply. J Pediatr 2019; 214:244-245. [PMID: 31351681 DOI: 10.1016/j.jpeds.2019.06.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 06/21/2019] [Indexed: 11/19/2022]
Affiliation(s)
- Catherine A Chapin
- Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
| | - Estella M Alonso
- Northwestern University Feinberg School of Medicine and Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois
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42
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Chapin CA, Horslen SP, Squires JE, Lin H, Blondet N, Mohammad S, Alonso EM. Corticosteroid Therapy for Indeterminate Pediatric Acute Liver Failure and Aplastic Anemia with Acute Hepatitis. J Pediatr 2019; 208:23-29. [PMID: 30770193 DOI: 10.1016/j.jpeds.2018.12.042] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Revised: 11/16/2018] [Accepted: 12/18/2018] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To examine the characteristics and outcomes of a multicenter patient cohort with indeterminate pediatric acute liver failure (IND-PALF) and with aplastic anemia with acute hepatitis treated with corticosteroids. STUDY DESIGN Retrospective study of patients age 1-17 years with IND-PALF and aplastic anemia with acute hepatitis who presented between 2009 and 2018 to 1 of 4 institutions and were treated with corticosteroids for presumed immune dysregulation. RESULTS Of 28 patients with IND-PALF (median of 4.0 years of age [range 1-16] and 71% male) 71% (n = 20) were treated with 0.5-4 mg/kg/day of intravenous methylprednisolone, and 8 patients received 10 mg/kg/day followed by a taper. By 21 days postcorticosteroid initiation, 14 patients (50%) underwent liver transplantation, 13 patients (46%) recovered with their native liver, and 1 patient (4%) died. Patients who recovered with their native liver received a median of 139 days (range 19-749) of corticosteroid therapy, with a median of 12 days (range 1-240) to international normalized ratio ≤1.2. Patients with aplastic anemia with acute hepatitis (n = 6; median of 9.5 years of age [range 1-12], 83% male), received 1-2 mg/kg/day of methylprednisolone for a median of 100 days (range 63-183), and all recovered with their native liver. One patient with IND-PALF and 2 patients with aplastic anemia with acute hepatitis developed a serious infection within 90 days postcorticosteroid initiation. CONCLUSIONS Many patients with IND-PALF or aplastic anemia with acute hepatitis that were treated with corticosteroids improved, but survival with native liver may not be different from historical reports. A randomized controlled trial exploring the benefits and risks of steroid therapy is needed before it is adopted broadly.
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Affiliation(s)
- Catherine A Chapin
- Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Simon P Horslen
- Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA
| | - James E Squires
- Department of Pediatrics, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA
| | - Henry Lin
- Department of Pediatrics; The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Niviann Blondet
- Department of Pediatrics, Seattle Children's Hospital, University of Washington School of Medicine, Seattle, WA
| | - Saeed Mohammad
- Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
| | - Estella M Alonso
- Department of Pediatrics, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL
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43
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Benmoussa A, Amine AM, Tissir R, Tazi I. [Severe acquired marrow aplasia and seronegative autoimmune hepatitis: a rare and serious association]. Pan Afr Med J 2019; 34:132. [PMID: 33708301 PMCID: PMC7906552 DOI: 10.11604/pamj.2019.34.132.20773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 03/30/2019] [Indexed: 12/03/2022] Open
Abstract
Les aplasies médullaires post hépatitiques sont des aplasies sévères survenant dans les 6 mois suivant au moins un épisode d'hépatite clinique d'installation rapide généralement séronégative pour les virus d'hépatite connus. Nous rapportons le cas d'un patient de 28 ans présentant une hépatite auto-immune révélée par un ictère avec hépatomégalie et cytolyse hépatique et confirmée par une ponction biopsie hépatique; se compliquant 4 mois plutard par l'apparition d'une pancytopénie liée à une aplasie médullaire sévère.
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Affiliation(s)
| | | | - Rajaa Tissir
- Service d'Hématologie, CHU Mohammed VI, Marrakech, Maroc
| | - Illias Tazi
- Service d'Hématologie, CHU Mohammed VI, Marrakech, Maroc
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44
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Mori T, Onishi Y, Ozawa Y, Kato C, Kai T, Kanda Y, Kurokawa M, Tanaka M, Ashida T, Sawayama Y, Fukuda T, Ichinohe T, Atsuta Y, Yamazaki H. Outcome of allogeneic hematopoietic stem cell transplantation in adult patients with hepatitis-associated aplastic anemia. Int J Hematol 2019; 109:711-717. [DOI: 10.1007/s12185-019-02644-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 04/01/2019] [Accepted: 04/02/2019] [Indexed: 12/18/2022]
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45
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Abstract
Aplastic anemia is a rare complication of viral hepatitis. We present 3 cases of hepatitis-associated aplastic anemia after hepatitis A virus infection. One of our cases is the first reported case of hepatitis-associated aplastic anemia after fulminant hepatitis A infection. Patient characteristics were consistent with older reports with regard to age and sex. All 3 patients were male individuals under the age of 20. In addition, all 3 patients had A+ blood group. Outcomes in our series were poor because of the unavailability of antithymocyte globulin and bone marrow transplantation.
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46
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Etu-Efeotor TP, Omunakwe HE. Anemia in Pregnant Women with Hepatitis B Viral DNA in Port Harcourt, Nigeria. J Glob Infect Dis 2019; 11:86-87. [PMID: 31198314 PMCID: PMC6555237 DOI: 10.4103/jgid.jgid_147_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Affiliation(s)
- Theodora P Etu-Efeotor
- Department of Haematology, Niger-Delta University Teaching Hospital, Bayelsa State, Nigeria
| | - Hannah E Omunakwe
- Department of Pathology, Rivers State University Teaching Hospital, Port Harcourt, Nigeria
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47
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Affiliation(s)
- Neal S Young
- From the Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD
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48
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Chapin CA, Burn T, Meijome T, Loomes KM, Melin-Aldana H, Kreiger PA, Whitington PF, Behrens EM, Alonso EM. Indeterminate pediatric acute liver failure is uniquely characterized by a CD103 + CD8 + T-cell infiltrate. Hepatology 2018; 68:1087-1100. [PMID: 29603342 DOI: 10.1002/hep.29901] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 02/28/2018] [Accepted: 03/23/2018] [Indexed: 12/16/2022]
Abstract
UNLABELLED The cause of pediatric acute liver failure (PALF) is unknown in up to 40% of cases. Evidence suggests that aberrant immune system activation may play a role. We hypothesized that indeterminate PALF cases would exhibit a unique pattern of hepatic inflammation. This was a retrospective and prospective study of PALF cases due to indeterminate (iPALF), autoimmune hepatitis, or known diagnosis (dPALF) etiology. Liver tissue sections were stained with immunohistochemical markers for cytotoxic T-cells (cluster of differentiation 8 [CD8]), perforin, and tissue resident memory T-cells (CD103) and scored as minimal, moderate, or dense. Lymphocytes were isolated from liver tissue for T-cell receptor beta sequencing and flow-cytometric studies. Thirty-three iPALF, 9 autoimmune hepatitis, and 14 dPALF cases were included. Dense hepatic infiltrates of CD8+ T-cells were found in 27 (82%) iPALF cases compared to 1 (7%) dPALF case (P < 0.0001). Perforin staining was dense or moderate in 19 (73%) of 26 iPALF cases compared to minimal in all 7 dPALF cases (P = 0.004); 16 (62%) of 26 iPALF cases had dense CD103 staining compared to none of the 6 dPALF cases (P = 0.001). T-cell receptor beta sequencing of iPALF cases demonstrated increased clonality compared to dPALF and control cases. Flow cytometry and immunohistochemistry revealed that iPALF intrahepatic leukocytes were predominantly tissue resident memory CD8+ T-cells. CONCLUSION Indeterminate PALF is characterized by a dense CD8+ T-cell hepatic infiltrate consistent with expansion of a tissue resident memory T-cell phenotype; CD8+ T-cells are a biomarker of immune dysregulation in iPALF and may be used to better identify and define this group. (Hepatology 2018).
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Affiliation(s)
- Catherine A Chapin
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Thomas Burn
- Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - Tomas Meijome
- Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - Kathleen M Loomes
- Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - Hector Melin-Aldana
- Department of Pathology and Laboratory Medicine, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Portia A Kreiger
- Department of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - Peter F Whitington
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
| | - Edward M Behrens
- Department of Pediatrics, University of Pennsylvania, Perelman School of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA
| | - Estella M Alonso
- Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL
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49
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Abstract
Hepatitis-associated aplastic anemia (HAAA) is a variant of acquired aplastic anemia in which bone marrow failure follows the development of an acute episode of seronegative hepatitis. HAAA occurs most frequently in male children and is lethal if left untreated. Antilymphocyte globulin, antithymocyte globulin, and allogeneic bone marrow transplantation have been used in the treatment of this disease. In this work, we report the case of a 3-year-old boy with HAAA treated successfully with immunosuppressive therapy.
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50
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Botero V, García VH, Aristizabal AM, Gomez C, Perez P, Caicedo LA, Echeverri GJ. Hepatitis A, cardiomyopathy, aplastic anemia, and acute liver failure: A devastating scenario. Transpl Infect Dis 2018; 20:e12842. [PMID: 29359844 DOI: 10.1111/tid.12842] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 09/14/2017] [Accepted: 09/24/2017] [Indexed: 11/30/2022]
Abstract
Hepatitis A virus (HAV) causes an acute infection and is usually asymptomatic in children. When clinical manifestations appear, these include choluria, jaundice, and abdominal pain. Although infrequent, extra-hepatic manifestations related to HAV have been described, affecting the heart, bone marrow, blood vessels, and other tissues.A 10-year-old boy from a rural area presented with a 15-day history of malaise, fever, and jaundice; laboratory examinations were compatible with HAV infection. The patient turned encephalopathic and was remitted to our center, where laboratory examinations showed a medullary aplasia and fulminant hepatitis requiring a liver transplant that was performed 72 hours after admission. At 24 hours post transplant, the patient developed a cardiomyopathy secondary to HAV, and intravenous immunoglobulin was administered. The patient is still alive and attending his medical check-ups.Although rare, extra-hepatic manifestations of HAV infection have been described in 14% of cases. The groups of patients affected are usually aged and present with high bilirubin levels. Acquired aplastic anemia and myocarditis caused by HAV are uncommon, and its pathophysiology has not yet been elucidated.HAV infection is usually asymptomatic in children, although extra-hepatic manifestations can appear requiring early detection and management.
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Affiliation(s)
- Verónica Botero
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
| | - Víctor H García
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
| | - Ana M Aristizabal
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
| | - Catalina Gomez
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
| | - Paola Perez
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
| | - Luis A Caicedo
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
| | - Gabriel J Echeverri
- Transplant Department, Fundación Valle del Lilí, Centre for Research on Advanced Surgery and Transplants (CICAT), Universidad Icesi, Cali, Colombia.,Clinical Research Centre, Fundación Valle del Lili, Cali, Colombia.,Centre for Research in Advanced Surgery and Transplants (CICAT), ICESI University, Cali, Colombia
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