Occult hepatitis B virus infection and reactivation in Africans in the context of the human immunodeficiency virus pandemic

人类免疫缺陷病毒大流行背景下非洲人的隐匿性乙型肝炎病毒感染和重新激活

• 批准号: 252558480
• 负责人: Professor Dr. Dieter Glebe
• 金额: --
• 依托单位: Institut für Medizinische Virologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/252558480?language=en
• 关键词: Occult; hepatitis; virus; infection; reactivation

Infections with hepatitis B virus (HBV) and human immunedeficiency virus (HIV) present a major global health challenge by causing massive impact on morbidity and mortality, especially in areas of high prevalence, like sub-Saharan Africa. Although much attention has been paid to HIV infection, because of the availability of a protective vaccine against HBV, this latter infection has been neglected. In recent years, a new scientific and medical challenge has emerged by the finding of life-long persistence of low-level replicating HBV-DNA in the liver, even in the presence of serological signs of resolved hepatitis B. This occult form of hepatitis B virus infections (OBI) is only detectable with high-end PCR techniques, requiring instrumentation and highly trained personnel, usually not available in developing countries. Moreover, the clinical implications of OBI are unclear and studies performed outside Africa, in areas of low HBV and HIV endemicity, cannot necessarily be extrapolated to Africa because of differences in host factors, epidemiology, transmission patterns and genotypes of the viruses between the two regions. In the last cycle of DFG funding we have successfully initiated a number of studies to establish prevalence of OBI in Africa and to study its clinical consequences. We published the first genotyping and prevalence study of HBV mono-infection carried out in Sudanese liver disease patients (Yousif et al., 2013). We further characterized HBV status in more than 358 HIV-infected Sudanese patients and determine the prevalence of OBI (15%) versus overt hepatitis B. Interestingly, co-infection with HDV was not prevalent in this Sudanese HIV/HBV cohort, but in the HBV monoinfected cohort (Manuscript attached). The main HBV genotype circulating in South Africa (A1) differ from those circulating in Sudan (D, E) and this will allow us to directly compare the impact of genotype/subgenotype on the development of OBI. In the South African study we have identified a number of mutants that could account for the HBsAg-negativity and we therefore wish to functionally characterize these together with selected mutants we discovered recently in the Sudanese cohort (Manuscript in preparation). In addition to the epidemiology, molecular and functional characterization of HBV in HIV infected individuals; we propose to look at host factors for OBI as well as OBI in end-stage renal disease.

B型肝炎病毒（HBV）和人类免疫缺陷病毒（HIV）感染对发病率和死亡率造成巨大影响，特别是在高流行率地区，如撒哈拉以南非洲，是一项重大的全球健康挑战。尽管人们对HIV感染给予了很大的关注，但由于可以获得针对HBV的保护性疫苗，后者的感染一直被忽视。近年来，一个新的科学和医学挑战已经出现，即发现低水平复制的HBV-DNA在肝脏中终生持续存在，即使在存在已消退的B型肝炎的血清学体征的情况下。这种隐匿形式的B型肝炎病毒感染（OBI）只能用高端PCR技术检测，需要仪器和训练有素的人员，通常在发展中国家无法获得。此外，OBI的临床意义尚不清楚，在非洲以外的HBV和HIV低流行地区进行的研究不一定能外推到非洲，因为这两个地区之间的宿主因素，流行病学，传播模式和病毒基因型存在差异。 在DFG资助的最后一个周期中，我们成功地启动了一些研究，以确定OBI在非洲的患病率并研究其临床后果。我们发表了在苏丹肝病患者中进行的HBV单一感染的第一个基因分型和患病率研究（Yousif等人，2013年）。 我们进一步描述了超过358例苏丹HIV感染患者的HBV状态，并确定了OBI（15%）与显性B型肝炎的患病率。有趣的是，HDV合并感染在苏丹HIV/HBV队列中并不普遍，但在HBV单一感染队列中普遍（随附Mandarin pt）。在南非（A1）流行的主要HBV基因型与在苏丹（D，E）流行的不同，这将使我们能够直接比较基因型/亚基因型对OBI发展的影响。在南非的研究中，我们已经确定了一些突变体，可以解释HBsAg阴性，因此，我们希望在功能上表征这些与我们最近在苏丹队列中发现的选定的突变体（Mandarapt准备）。 除了HIV感染者中HBV的流行病学、分子和功能特征外，我们还建议研究OBI的宿主因素以及终末期肾病中的OBI。