Current and future antiviral drug therapies of hepatitis B chronic infection

Abstract

Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem, affecting more than 350 million people worldwide. The natural course of the infection is dynamic and involves a complex interplay between the virus and the host's immune system. Currently the approved therapeutic regimens include pegylated-interferon (IFN)-α and monotherapy with five nucleos(t)ide analogues (NAs). Both antiviral treatments are not capable to eliminate the virus and do not establish longterm control of infection after treatment withdrawal. IFN therapy is of finite duration and associates with low response rates, liver decompensating and numerous side effects. NAs are well-tolerated therapies but have a high risk of drug resistance development that limits their prolonged use. The imperative for the development of new approaches for the treatment of chronic HBV infection is a challenging issue that cannot be over-sided. Research efforts are focusing on the identification and evaluation of various viral replication inhibitors that target viral replication and a number of immunomodulators that aim to restore the HBV specific immune hyporesponsiveness without inducing liver damage. This review brings together our current knowledge on the available treatment and discusses potential therapeutic approaches in the battle against chronic HBV infection. Core tip: Despite significant improvement in the management of chronic hepatitis B virus (HBV) it remains a public health problem. Current therapeutic regimens include pegylated-interferon (IFN)-α and nucleos(t)ide analogues (NAs). Both treatments do not eradicate the virus and have numerous limitations. IFN therapy is of finite duration and has low response rates while longterm NA therapies have a high risk of drug resistance. The development of new therapeutic approaches is imperative. This review brings together current treatments and the ongoing research efforts on evaluating potential therapeutic strategies that target the suppression of HBV replication the restoration of the weak immune responses against HBV.

Targeting Inflammation in Cancer Prevention and Therapy

“…For patients who have already been infected by HBV and developed chronic hepatitis, secondary prevention becomes more important. Currently antiviral drugs used in patients with chronic hepatitis B include the immunomodulator pegylated IFN-α and oral nucleos(t)ide analogues(147). IFNs activate various IRF family members that regulates transcription of numerous targets, including genes involved in control of viral mRNA translation or degradation(147).…”

“…Currently antiviral drugs used in patients with chronic hepatitis B include the immunomodulator pegylated IFN-α and oral nucleos(t)ide analogues(147). IFNs activate various IRF family members that regulates transcription of numerous targets, including genes involved in control of viral mRNA translation or degradation(147). However, the mechanism of IFN-α-mediated cell protection against viral infection is not fully understood.…”

2′‐Fluoro‐6′‐methylene carbocyclic adenosine and its phosphoramidate prodrug: A novel anti‐HBV agent, active against drug‐resistant HBV mutants

“…The rate of resistance is high for the use of nucleos(t)ides, such as LMV/LAM, LdT, and adefovir, in comparison to ETV and tenofovir . Due to high risks of cross‐resistance, it is more challenging to manage the preexisting antiviral resistance . Primary mutations usually alter the HBV polymerase domain, which affects the inhibitory effect of antiviral nucleos(t)ides .…”

Tratamiento actual y nuevas terapias contra la infección crónica por el virus de la Hepatitis B

“…Petersen y colaboradores demostraron que es capaz de prevenir la infección por el VHB en cultivos de hepatocitos y ratones humanizados, así como el establecimiento de la infección por VHD. Entre sus efectos adversos está la inhibición del transporte de ácidos biliares (64). Otros inhibidores conocidos del NTCP son la ciclosporina A y B, ezetimiba, irbesartán, ritonavir, bosentán, propranolol, entre otros.…”