Research priorities for the discovery of a cure for chronic hepatitis B: Report of a workshop

Abstract

In early 2017, the Hepatitis B Foundation invited 30 experts in the fields of hepatitis B and liver cancer research to identify projects they deemed important to the goal of finding a cure for chronic hepatitis B and D and the diseases with which these viral infections are associated. They were also asked to identify general categories of research and to prioritize sub-project topics within those areas. The experts generally agreed on broadly defined areas of research, but there was usually little difference between the highest and lowest scoring projects; for the most part, all programs described in this document were considered valuable and necessary. An executive summary of this discussion was recently published (Alter et al., Hepatology 2017). The present manuscript reports the areas of research identified by the workshop participants, provides a brief rationale for their selection, and attempts to express differences among the priorities assigned to each area of research, when such distinctions were expressed.

Combination of Entecavir/Peginterferon Alfa‐2a in Children With Hepatitis B e Antigen–Positive Immune Tolerant Chronic Hepatitis B Virus Infection

“…These results suggest the possibility of cure of chronic HBV infection, at least in children, and call for increased efforts to find antiviral agents for hepatitis B that might be combined with nucleoside analogs with or without peginterferon. Clearly, identifying other viral and host targets for antiviral therapy of hepatitis B is an important challenge and should be a priority in the search for a “cure” of this important viral infection for both children and adults …”

Hepatitis B virus X protein modulates upregulation of DHX9 to promote viral DNA replication

“…As a regulatory protein, HBx modulates transcription activation by binding to transcription factors, such as activating protein 1 (AP-1) and CREB (Ng & Lee, 2011;Williams & Andrisani, 1995), although it does not bind to DNA directly. Therefore, understanding the interaction of HBx and the cellular proteins that regulate viral replication is essential for the design of novel anti-HBV therapeutics (Block et al, 2018). Therefore, understanding the interaction of HBx and the cellular proteins that regulate viral replication is essential for the design of novel anti-HBV therapeutics (Block et al, 2018).…”

“…In addition, HBx can interact with the cellular proteasome complex to degrade the host restriction factor SMC5/6 to activate cccDNA transcription (Decorsiere et al, 2016;Murphy et al, 2016). Therefore, understanding the interaction of HBx and the cellular proteins that regulate viral replication is essential for the design of novel anti-HBV therapeutics (Block et al, 2018).…”

Virus-like vesicles expressing multiple antigens for immunotherapy of chronic hepatitis B

“…The resulting VLV titers routinely exceeded 10 9 pfu/ml. 8 To mitigate potential risks of homologous recombination of the repeating T2A peptide sequences in the 3xT2A construct during VLV replication, we designed and evaluated an alternative construct, Mix2A, in which we replaced the two T2A peptides with the porcine teschovirus-1 (P2A) and equine rhinitis A virus (E2A) peptides (24) ( Fig 1A). These peptides are structurally similar, but encoded by different nucleotide sequences.…”

“…However, adverse effects of IFN treatment, lack of complete HBV clearance, and development of drug resistance after prolonged treatment with nucleos(t)ides emphasize the unmet need for alternative therapeutic approaches that can lead to functional cure (3,7,8).…”