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

乙型肝炎病毒（HBV）和人体免疫缺陷病毒（HIV）的感染对发病率和死亡率造成巨大影响，特别是在撒哈拉以南非洲等高流行地区，是一项重大的全球卫生挑战。尽管对艾滋病毒感染给予了很大的关注，但由于乙型肝炎病毒保护性疫苗的可用性，后一种感染一直被忽视。近年来，出现了一项新的科学和医学挑战，即发现肝脏中存在终身持续的低水平复制HBV-DNA，即使存在已解决的乙型肝炎的血清学迹象。这种隐匿形式的乙型肝炎病毒感染（OBI）只能用高端PCR技术检测，需要仪器和训练有素的人员，通常在发展中国家不具备。此外，OBI的临床意义尚不清楚，在非洲以外的低乙型肝炎病毒和艾滋病毒流行地区进行的研究不一定能推断到非洲，因为这两个地区在宿主因素、流行病学、传播模式和病毒基因型方面存在差异。在DFG供资的上一个周期中，我们成功地启动了若干研究，以确定非洲OBI的流行情况并研究其临床后果。我们发表了首个在苏丹肝病患者中进行的HBV单感染基因分型和流行研究（Yousif et al., 2013）。我们进一步分析了358名苏丹HIV感染患者的HBV状态，并确定OBI（15%）与显性乙肝的患病率。有趣的是，在苏丹HIV/HBV队列中，HDV合并感染并不普遍，但在HBV单感染队列中（论文附件）。南非流行的主要HBV基因型（A1）与苏丹流行的HBV基因型（D， E）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可以解释hbsag阴性的突变体，因此我们希望将这些突变体与我们最近在苏丹队列中发现的精选突变体一起进行功能表征（手稿正在准备中）。除了流行病学，HBV在HIV感染者中的分子和功能特征；我们建议研究OBI的宿主因素以及终末期肾脏疾病的OBI。

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.