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

• Applicant: Professor Dr. Dieter Glebe
• Co-Applicants: Professorin Dr. Anna Kramvis; Professor Dr. Hatim M.Y. Mudawi
• Subject Area: Virology
• Term: from 2014 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 252558480

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.

• DFG Programme: Research Grants
• International Connection: South Africa, Sudan