| Invited Lecture(JSGE) |
| Thu. October 31st 9:00 - 9:30 Room 1: Kobe International Exhibition Hall No.2 Building Hall (North) |
| Therapeutic approaches to viral hepatitis | |||
| Edward Gane | |||
| University of Auckland | |||
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| Globally, 350 million people are living with chronic hepatitis B or C and almost 1 million will die each year from complications of decompensated cirrhosis or hepatocellular carcinoma. Many more suffer chronic ill health and discrimination. In 2016, the World Health Assembly agreed to global elimination of both hepatitis B and hepatitis C by 2030. Elimination of HepC is possible with pangenotypic DAAs SOF/VEL and GLE/PIB, with SVR rates >98% across all populations. The only barrier to global HepC elimination is the low rate of diagnosis and linkage to care. Elimination of HepB is possible through universal neonatal immunization but this will take another 90 years, with an additional 80 million deaths most from hepatocellular carcinoma. The only way to reduce mortality is through earlier diagnosis and treatment of adults living with chronic HBV infection. Current oral nucleoside inhibitors are safe and highly effective but must be administered lifelong and require monitoring for virologic breakthrough and toxicity. Hence there is therefore great interest in developing a finite treatment strategy that will achieve durable off-treatment clearance of HBsAg and HBV DNA, so-called Functional Cure. Better understanding of both the HBV lifecycle and the host immune responses provides many different targets for antiviral and immunomodulatory approaches. New core inhibitors achieve profound suppression of DNA/RNA and reduce HBsAg levels through inhibition of cccDNA replenishment. Other antiviral approaches to suppress HbsAg include translation inhibitors, RNA destabilizers, nucleic acid polymers and monoclonal antibodies. siRNAs can achieve HBsAg suppression but not loss. In comparison the new ASOs bepiroversin and AHB-137 do achieve on-treatment HBsAg loss in 10-30% patients. Rapid suppress of HBsAg could restore HBV-specific T-cell immunity and enhance the efficacy of novel immunotherapies such as checkpoint inhibitors, therapeutic vaccines and TLR agonists. Initial HBV Cure will combine multiple agents that inhibit replication, reduce HBV antigen burden and restore HBV-specific immune control and are likely to target patient populations most likely to respond. The most promising approaches for HBV cure are the new gene editing strategies of CRISPR and epigenic modulation which eradicate or silence both cccDNA integrated HBV DNA. The first studies are about to start later this year and could potentially cure all HbsAg positive patients regardless of phase of infection. |
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