Review article: hepatitis B—current and emerging therapies

Abstract

Background The hepatitis B virus (HBV) affects an estimated 290 million individuals worldwide and is responsible for approximately 900 000 deaths annually, mostly from complications of cirrhosis and hepatocellular carcinoma. Although current treatment is effective at preventing complications of chronic hepatitis B, it is not curative, and often must be administered long term. There is a need for safe, effective, finite duration curative therapy. Aim Our aim was to provide a concise, up to date review of all currently available and emerging treatment options for chronic hepatitis B. Methods We conducted a search of PubMed, clinicaltrials.gov, major meeting abstracts and pharmaceutical websites for publications and communications on current and emerging therapies for HBV. Results Currently approved treatment options for chronic hepatitis B include peginterferon alpha‐2a and nucleos(t)ide analogues. Both options do not offer a ‘complete cure’ (clearance of covalently closed circular DNA (cccDNA) and integrated HBV DNA) and rarely achieve a ‘functional cure’ (hepatitis B surface antigen (HBsAg) loss). An improved understanding of the viral lifecycle, immunopathogenesis and recent advances in drug delivery technologies have led to many novel therapeutic approaches that are currently being evaluated in clinical trials including targeting of viral entry, cccDNA, viral transcription, core protein, and release of HBsAg and HBV polymerase. Additionally, novel immunological approaches that include targeting the innate and adaptive immune system and therapeutic vaccination are being pursued. Conclusion The breadth and scope of novel therapies in development hold promise for regimen/s that will achieve functional cure.

Meta-analysis of the occurrence of hepatocellular carcinoma after the treatment of entecavir and tenofovir for chronic hepatitis B

“…Now ETV and TDF can only inhibit the replication of the virus, but can not fully eliminate it; that is to say, it is possible to clear the covalently closed circular DNA, yet hard to fulfill the functional cure, which means the loss of HBsAg. [ 23 , 28 , 29 ]…”

“…Now ETV and TDF can only inhibit the replication of the virus, but can not fully eliminate it; that is to say, it is possible to clear the covalently closed circular DNA, yet hard to fulfill the functional cure, which means the loss of HBsAg. [23,28,29] A report from Hong Kong involves 222 cases of patients with CHB who receive primary treatment. These patients have received a 5-year treatment of ETV, and the result shows that HBVDNA can't be detected in 97.1% of the patients (<20 IU/ mL), the serological conversion of HBeAg is fulfilled in 66.9% of the patients, HBsAg disappears in 1 case, and the 5-year cumulative drug resistance rate is 1.2%.…”

Prospective use of amniotic mesenchymal stem cell metabolite products for tissue regeneration

“…Degenerative diseases, physical injury to organs, and damage due to chronic conditions such as diabetes can cause organ function loss [1][2][3]. In the early stages of disease, pharmacological drug therapy is the first-line treatment choice, but it has some drawbacks.…”

The efficacy and safety of adding on or switching to peginterferon α‐2b in HBeAg‐positive chronic hepatitis B patients with long‐term entecavir treatment: a multicentre randomised controlled trial

“…Given that novel therapeutic regimens targeting multiple steps in HBV life cycle are still in clinical testing, [17][18][19] it is of great significance to explore the treatment combinations of currently available agents to maximise response rates in CHB patients with long-term NA therapy. In recent years, accumulating data have shown that combination strategies, including switching from NA administration to PEG-IFN or addition of PEG-IFN to NA therapy, can effectively improve the rates of serological response.…”