Thakur Warkha, Anwar Nida, Samad Shafaq, Fatima Naveena, Ahmed Rehana, Tariq Faryal, Ashfaq Javeria, Sharif Sumaira, Borhany Munira
Hematology, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, PAK.
Hematology and Bone Marrow Transplantation, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, PAK.
Cureus. 2022 Sep 12;14(9):e29079. doi: 10.7759/cureus.29079. eCollection 2022 Sep.
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.
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.
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.
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.
再生障碍性贫血(AA)的特征是全血细胞减少和骨髓细胞减少,且不存在异常浸润或网硬蛋白纤维化增加。由于细胞数量减少以及与其他骨髓衰竭综合征的形态学特征重叠,AA的诊断有时具有挑战性。肝炎相关性再生障碍性贫血(HAAA)是一种罕见的变异型,患者通常先出现黄疸和肝炎,随后几乎在6个月内出现全血细胞减少。肝炎后再生障碍性贫血约占病例的1%-5%,并且这些病例对已知肝炎病毒检测也均为阴性。目前关于再生障碍性贫血与肝炎相关性的文献有限,在我们地区尚未见国家级的报道。由于与西方世界相比,再生障碍性贫血在东南亚相对更为普遍,且肝炎在我们的人群中是一种常见疾病,本研究的主要目的是评估肝脏状况并确定再生障碍性贫血诊断时肝炎的相关性。
在获得患者知情同意后,于2019年11月至2020年12月在卡拉奇国家血液疾病和骨髓移植研究所开展了一项横断面研究。该研究纳入了所有未经治疗的获得性再生障碍性贫血患者,这些患者既往无服用类固醇、免疫抑制治疗或放化疗的病史。进行了肝功能检查、全血细胞计数、凝血酶原时间(PT)和活化部分凝血活酶时间检测,以及病毒检测(甲型肝炎病毒、乙肝病毒、丙肝病毒和艾滋病毒)。使用SPSS 23版(IBM公司,纽约州阿蒙克)进行统计分析。对定量变量计算均值和标准差,对定性变量报告百分比和频率。采用t检验观察组间的主要差异,p值<0.05被认为具有统计学意义。
在总共351例患者中,29例(8.2%)再生障碍性贫血患者病毒肝炎检测呈阳性。甲型肝炎是最常见的肝炎类型(4.0%),其次是丙型肝炎(3.7%)。有肝炎和无肝炎患者的血小板计数比较具有统计学意义(p值<0.05)。再生障碍性贫血有肝炎和无肝炎患者的血小板计数和PT存在显著统计学差异(p值<0.0001)。
总体而言,本研究表明,再生障碍性贫血患者中<10%的患者甲型、乙型和丙型肝炎筛查呈阳性,且血小板计数较低,有肝炎和无肝炎患者之间的PT具有统计学意义。在我们所在地区普遍存在的肝炎可能与再生障碍性贫血有重要的因果关联。再生障碍性贫血患者在诊断时应进行肝功能和病毒性肝炎筛查。除了甲型、乙型和丙型肝炎以及艾滋病毒外,还应筛查其他肝炎病因,如细小病毒B19、人类疱疹病毒16和腺病毒,这些未包括在常规诊断病毒检测项目中。