Search for a cure for chronic hepatitis B infection: How close are we?

Abstract

Chronic hepatitis B (CHB) remains a significant unmet medical need, with 240 million chronically infected persons worldwide. It can be controlled effectively with either nucleoside/nucleotide-based or interferon-based therapies. However, most patients receiving these therapies will relapse after treatment withdrawal. During recent years, the advances in molecular biology and immunology have enabled a better understanding of the viral-host interaction and inspired new treatment approaches to achieve either elimination of the virus from the liver or durable immune control of the infection. This review aims to provide a brief overview on the potential new therapies that may overcome the challenge of persistent CHB infection in the near future.

Keywords: Antiviral therapy; Covalently closed circular DNA; Drug target; Hepatitis B; Immunomodulator.

Figures

Figure 1

Replicative cycle of hepatitis B virus and the respective targets of the current and experimental therapeutic agents. Modified from Chan et al[18], with permission granted by Elsevier (Copyright owner). ER: Endoplasmic reticulum; HAP12: Heteroaryldihydropyrimidines 12; HBs protein L, M, S: HBs protein Large, Medium, Small; HBV: Hepatitis B virus; HBsAg: Hepatitis B virus antigen; RC-DNA: Relaxed circular DNA; RNAi: RNA interference; shRNA: Short/small hairpin RNA; cccDNA: Covalently closed circular DNA; KAT: Kynurenine aminotransferase; LTβR: Lymphotoxin beta receptor; TALEN: Transcription activator-like effector nuclease; ZFN: Zinc finger nuclease.