Molecular characterization of hepatitis B virus (HBV) isolated from a pediatric case of acute lymphoid leukemia, with a delayed response to antiviral treatment: a case report.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is effectively used as the first-line antiviral for chronic hepatitis B virus (HBV) infection in adults and children older than 12 years. To date, no confirmed case of virologic breakthrough (VBT) in a pediatric case has been reported. CASE PRESENTATION: Here we describe a case of a 5-year old, asymptomatically infected with HBV infection two months after chemotherapy for precursor B acute lymphoblastic leukemia (ALL). Although the 5-year old male is South African, his family originated from Guinea. At the end of the one-year follow-up, the infection progressed to chronic HBV infection, with a high viral load. At 36 weeks (8 months) post-treatment with lamivudine (LAM), there was a partial virologic response (PVR) and after 61 weeks (14 months), he was switched to TDF rescue monotherapy. Even with TDF treatment, he still experienced VBT and subsequent PVR. The full-length genome of HBV isolated 78 weeks after the switch to rescue TDF monotherapy was sequenced and belonged to genotype E. In addition to the LAM mutations (rtS256G and rtM267L), missense mutations in B-cell, T-cell, HLA class I and II-restricted epitopes emerged, which were to evade and escape host surveillance, leading to delayed viral clearance, persistence and disease progression. Two further events of VBT occurred between weeks 113 and 141 of TDF rescue-therapy. Viral loads and liver enzymes are normalizing progressively with long-term therapy. CONCLUSION: Although the host immune reconstitution may be delayed, prolonged TDF treatment was effective in treating this pediatric case of HBV infection with VBT and PVR.

Genotype E: The neglected genotype of hepatitis B virus.

Hepatitis B virus (HBV) (sub)genotypes A1, D3 and E circulate in sub-Saharan Africa, the region with one of the highest incidences of HBV-associated hepatocellular carcinoma globally. Although genotype E was identified more than 20 years ago, and is the most widespread genotype in Africa, it has not been extensively studied. The current knowledge status and gaps in its origin and evolution, natural history of infection, disease progression, response to antiviral therapy and vaccination are discussed. Genotype E is an African genotype, with unique molecular characteristics that is found mainly in Western and Central Africa and rarely outside Africa except in individuals of African descent. The low prevalence of this genotype in the African descendant populations in the New World, phylogeographic analyses, the low genetic diversity and evidence of remnants of genotype E in ancient HBV samples suggests the relatively recent re-introduction into the population. There is scarcity of information on the clinical and virological characteristics of genotype E-infected patients, disease progression and outcomes and efficacy of anti-HBV drugs. Individuals infected with genotype E have been characterised with high hepatitis B e antigen-positivity and high viral load with a lower end of treatment response to interferon-alpha. A minority of genotype E-infected participants have been included in studies in which treatment response was monitored. Of concern is that current guidelines do not consider patients infected with genotype E. Thus, there is an urgent need for further large-scale investigations into genotype E, the neglected genotype of HBV.

Global and regional dispersal patterns of hepatitis B virus genotype E from and in Africa: A full-genome molecular analysis.

Description of the spatial characteristics of viral dispersal is important in understanding the history of infections. Nine hepatitis B virus (HBV) genotypes (A-I), and a putative 10th genotype (J), with distinct geographical distribution, are recognized. In sub-Saharan Africa (sub)-genotypes A1, D3 and E circulate, with E predominating in western Africa (WA), where HBV is hyperendemic. The low genetic diversity of genotype E (HBV/E) suggests its recent emergence. Our aim was to study the dispersal of HBV/E using full-length, non-redundant and non-recombinant sequences available in public databases. HBV/E was confirmed, and the phylogeny reconstruction performed using maximum likelihood (ML) with bootstrapping. Phylogeographic analysis was conducted by reconstruction of ancestral states using the criterion of parsimony on the estimated ML phylogeny. 46.5% of HBV/E sequences were found within monophyletic clusters. Country-wise analysis revealed the existence of 50 regional clusters. Sequences from WA were located close to the root of the tree, indicating this region as the most probable origin of the HBV/E epidemic and expanded to other geographical regions, within and outside of Africa. A localized dispersal was observed with sequences from Nigeria and Guinea as compared to other WA countries. Based on the sequences available in the databases, the phylogenetic results suggest that European strains originated primarily from WA whereas a majority of American strains originated in Western Central Africa. The differences in regional dispersal patterns of HBV/E suggest limited cross-border transmissions because of restricted population movements.