Section of Gastroenterology, Hepatology and Nutrition, and the Digestive Health Institute, Children's Hospital Colorado, University of Colorado Denver School of Medicine.
Section of Pathology and Lab Services, Children's Hospital Colorado, University of Colorado Denver School of Medicine.
J Pediatr Gastroenterol Nutr. 2021 Feb 1;72(2):194-201. doi: 10.1097/MPG.0000000000002940.
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.
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.
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.
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.
肝炎相关性再生障碍性贫血（HAAA）是一种可能危及生命的疾病，目前尚无明确的治疗指南。本研究旨在描述儿童 HAAA 的临床表现、评估、组织病理学和治疗结果，以指导未来的研究，并为这种罕见疾病制定标准化的治疗指南。
对 2016 年至 2019 年期间在科罗拉多儿童医院就诊的 4 例 HAAA 患儿进行回顾性病历分析。收集患者的临床表现、评估、骨髓和肝脏病理、干预措施和临床过程。对肝脏活检进行免疫组织化学检查。
我们治疗了 4 例无肝衰竭的 HAAA 患者。所有患者均有全身炎症反应过度和 CD8+T 细胞为主的肝脏组织浸润的证据。其中 1 例存在易患免疫介导性疾病的基因突变，但其他基因检测均为阴性。在 4 例患者中的 3 例，肝炎对标准的类固醇、硫唑嘌呤或他克莫司治疗反应不佳；然而，在更积极的免疫抑制治疗后，包括抗胸腺细胞球蛋白（ATG）在严重再生障碍性贫血（sAA）的标准免疫抑制治疗（IST）剂量下，肝炎的生化缓解得以持续，其中 2 例患者接受了造血干细胞移植（HSCT）；1 例作为一线治疗，1 例用于治疗难治性 sAA。
我们发现基于 ATG 的 IST 诱导了类固醇难治性 HAAA 患者的肝炎缓解。这也是治疗严重再生障碍性贫血的一种合适的初始治疗方法，尽管可能无法预防需要进行 HSCT。我们建议在标准剂量方案下使用马源 ATG 进行 IST 是一种治疗方法，在某些情况下可以在治疗过程早期考虑使用，并且可以导致肝炎和 sAA 的持续缓解。这应与儿科血液病专家合作进行。
