International Session（Workshop）1(JSGE・JSH・JSGCS)
Thu. November 2nd   14:30 - 17:00   Room 11: Portopia Hotel South Wing Topaz
IS-W1-Keynote Lecture2
 Therapeutic Approach to HBV Cure
Henry LY Chan
The Chinese University of Hong Kong
HBsAg seroclearance is associated with excellent prognosis and is regarded as functional cure, which is the immediate goal of new hepatitis B drug development. Continuous viral suppression with nucleos(t)ide analogues (NA) can hardly reduce HBsAg level in the serum because most HBsAg are produced by integrated HBV DNA. Hence, HBsAg seroclearance is an immune mediated phenomenon.
In the last decade, many new direct antiviral treatments have been investigated. Capsid assembly inhibitors can reduce HBV RNA but have minimal effect on HBsAg reduction. RNA interference by siRNA and antisense oligonucleotides can reduce HBsAg level by 2-3 logs in 6-12 months. Combination of peginterferon can further improve HBsAg reduction with siRNA. There are also early encouraging data on the combination of nucleic acid polymer and peginterferon among NA treated patients, but bigger trials are required to confirm the efficacy of this strategy.
Owing to the undesirable adverse effects of peginterferon, other less toxic immune modulators are under development. Early data on TLR-8 agonist suggested a dose dependent immune enhancement. The early trials of therapeutic vaccine in NA treated patients are largely negative, but newer versions of therapeutic vaccine are under development. There is also early data suggesting low dose nivolumab can induce HBsAg seroclearance. More studies are required to evaluate the safety and efficacy of these immune modulators in combination with direct antiviral agents in the search for functional cure of hepatitis B.
Index Term 1: Hepatitis B treatment
Index Term 2: HBsAg seroclearance
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