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[Hepatitis C can be cured: will hepatitis B become next?]
V P Chulanov1, A P Zueva2, D S Kostyushev3
1Central Research Institute of Epidemiology of Rospotrebnadzor, Moscow, Russia; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russian Federation, Moscow, Russia.
Insights
New therapies offer hope for chronic hepatitis B (CHB) and C (CHC) patients, with genome editing technologies like CRISPR/Cas showing promise for complete viral elimination, though still in early development.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- Chronic hepatitis B (CHB) and C (CHC) cause significant global mortality from cirrhosis and liver cancer.
- While CHC is curable, CHB management involves viral suppression with frequent relapses upon treatment cessation.
- Complete elimination of hepatitis B virus (HBV) is hindered by persistent, antiviral-resistant covalently closed circular DNA (cccDNA) in hepatocytes.
Purpose of the Study:
- To review current therapeutic strategies for CHB and CHC.
- To explore novel treatment modalities targeting different stages of the HBV life cycle.
- To assess the potential of emerging technologies, particularly genome editing, for achieving a functional or complete cure for CHB.
Main Methods:
- Review of recent advancements in antiviral therapeutics for CHC and CHB.
- Analysis of novel drug development targeting HBV entry, cccDNA, and viral assembly.
- Evaluation of immunotherapeutic approaches to enhance host responses.
- Assessment of genome editing technologies (TALENs, CRISPR/Cas) and RNA interference for HBV clearance.
Main Results:
- Hepatitis C is now curable with modern antivirals.
- Current CHB therapies suppress HBV replication but do not achieve a complete cure, with functional cure (HBsAg loss) being rare.
- Emerging therapies, including cccDNA inhibitors, genome editing, and immune modulators, show promise in experimental settings.
- Genome editing technologies, such as CRISPR/Cas, demonstrate potential for specific cccDNA degradation, offering a pathway to complete HBV elimination.
Conclusions:
- While significant progress has been made, particularly in CHC treatment, CHB remains a challenging disease requiring innovative therapeutic approaches.
- Novel direct-acting antivirals and immunotherapies are advancing CHB treatment, with potential for functional cure.
- Genome editing technologies represent a highly promising future strategy for achieving complete HBV eradication by targeting the persistent cccDNA reservoir, despite being in early developmental stages.
Abstract:
Chronic hepatitis B (CHB) and C (CHC) are one of the leading causes of cirrhosis and liver cancer with over a million of people dying annually from their consequences. In Russia CHB and CHC morbidity and related mortality show an upward trend. As a result of recent breakthroughs in antiviral therapeutics CHC became a curable disease. Modern therapeutics effectively suppress viral replication in CHB patients, but withdrawal of antivirals usually results in disease relapse. Loss of HBsAg required for the so called 'functional cure' is a very rare event. Moreover, 'complete cure' when the virus is entirely eliminated from the body is not possible due to a persistent form of covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) in hepatocytes refractory to modern antivirals. Today, there is a plethora of new promising medications being at different stages of development that target different steps of viral life cycle, including inhibitors of interaction between HBV and its entry receptor NTCP, inhibitors of HBV cccDNA, inhibitors of nucleocapsid assembly, technologies of genome editing (TALENs, CRISPR/Cas etc) and RNA-interference. In addition to direct acting antivirals, there is a number of approaches aimed at enhancement of the innate and adaptive immune responses. In experimental conditions, some of these approaches or their combinations help to achieve functional cure. However, complete elimination of the virus is possible only using technologies of genome editing, capable of specific cccDNA degradation. Nuclease systems are currently at their early stages of development, and there is a long way to prove their efficacy and safety. Nevertheless, highly promising results of the recent years leave no doubt that CRISPR/Cas systems and similar technologies can become the basis of CHB therapy.
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