Inhibiting the Secretion of Hepatitis B Surface Antigen (HBsAg) to Treat Hepatitis B Infection- a Review

Abstract

Chronic hepatitis B is a major global health issue, and has no known cure. Currently there are over 240 million people infected with the disease, and it leads to the death of over 686,000 people each year. A total of seven treatments which help to control the disease are currently available: interferon-based treatments (pegasys, and interferon alpha), and nucleoside and nucleotide analogs (Viread, Baraclude, Tyzeka, Hepsera, Epivir-HBV), but all require continuing treatment to maintain control of the disease. One of the definitions of a cure for hepatitis B virus (HBV) is the loss of hepatitis B surface antigen (HBsAg), the lipid envelope which surrounds the hepatitis B virus. The current interferon-based treatments, and nucleoside and nucleotide analogs give at most an approximately 10% rate of clearance of HBsAg. Other viral diseases such as HIV and hepatitis C have been most effectively treated with a combination of agents, and it is believed that the best opportunity for finding a cure for HBV will reside in a combination of therapies targeting different phases of the HBV lifecycle.A range of agents (small-molecules, natural products, macrocycles, and non-small molecules) have been described as having the ability to suppress the secretion of HBsAg (in vitro, as well as in vivo in animal models, pre-clinical models, and clinical trials), and this review will focus on an overview of the different agents, and different strategies being pursued to develop methods of inhibiting the secretion of HBsAg, with a view to the cure of HBV.

Keywords: HBV cure; HBsAg; Hepatitis B surface antigen; Hepatitis B virus; Secretion inhibition; macrocycles.