Chronic hepatitis B: Are we close to a cure?

Abstract

Approximately 300 million people worldwide are persistently infected with the hepatitis B virus and are at risk of developing hepatocellular carcinoma and liver cirrhosis, which can progress to end-stage liver disease. Despite the effectiveness of the current vaccination policy, the prevalence of the disease remains high, and the burden for health services is considerable. The currently available antiviral strategies are either poorly effective or only effective for non-curative suppression of viral replication. Recent efforts have been focused on improving the cure rate for chronic hepatitis B and developing strategies to eliminate infected cells. Several approaches are under evaluation, and these include targeting the virus at different stages of its life cycle and boosting the antiviral immune response. This article reviews these latest approaches and comments on their feasibility and potential translation into clinical applications.

The role of peginterferon in nucleos(t)ide‐analogue‐treated chronic hepatitis B patients: A review of published literature

“…4,14 PegIFN has a curative effect that is mediated by viral inhibition and immune restoration and enhancement. 3 Treatment with a finite course of PegIFN achieves higher HBsAg loss rates over time than NAs; HBsAg loss rate is 3-7% after 1 year of treatment with PegIFN 15,16 and can increase to up to 12% 5 years after discontinuation of therapy. 17 Furthermore, PegIFN therapy achieves HBeAg seroconversion in one-third of HBeAg-positive patients 15,18 and HBV-DNA <2000 copies/mL in 43% of HBeAg-negative patients 19 6 months post-treatment.…”

“…Whilst elimination of both viraemia and HBsAg followed by seroconversion to anti‐HBsAg antibodies is currently the most desirable endpoint, definite viral eradication and complete protection from reactivation can only be achieved by elimination of cccDNA from infected hepatocytes . New strategies for HBV elimination are being investigated; these include novel agents targetting cccDNA and host function directly, as well as immunotherapeutic approaches such as therapeutic vaccines …”

“…HBV‐related morbidities and hepatocellular carcinoma (HCC) are responsible for 0.5‐1.0 million deaths yearly, representing a major global health concern. A complete cure of chronic hepatitis B (CHB) is accomplished by the complete eradication of covalently closed circular DNA (cccDNA), which serves as the transcriptional template of HBV and a reservoir for future replication cycles . However, cccDNA is particularly stable and persistent.…”

“…PegIFN has a curative effect that is mediated by viral inhibition and immune restoration and enhancement . Treatment with a finite course of PegIFN achieves higher HBsAg loss rates over time than NAs; HBsAg loss rate is 3‐7% after 1 year of treatment with PegIFN and can increase to up to 12% 5 years after discontinuation of therapy .…”

“…A complete cure of chronic hepatitis B (CHB) is accomplished by the complete eradication of covalently closed circular DNA (cccDNA), which serves as the transcriptional template of HBV and a reservoir for future replication cycles. 2,3 However, cccDNA is particularly stable and persistent. Thus, clearance of hepatitis B surface antigen (HBsAg), a replication product that reflects the transcriptional activity of cccDNA, 2 is considered to be the closest event to a cure for CHB, with sustained off-therapy HBsAg loss recognized as the ideal endpoint of therapy.…”