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Dr VA Saraswat 06 December 2018

Approaches towards the management of HBV infection comprise virologic suppression, ‘functional’ cure, and complete or ‘virologic’ cure.
Virologic suppression – pharmaceutical suppression of HBV DNA and normal ALT-AST, histological inactivity, and ‘e’ seroconversion; ‘functional’ cure – sustained ‘off-drug’ suppression of HBsAg, HBeAg, HBV DNA, and cccDNA, normal ALT-AST, histological inactivity, and comparable with individuals with resolved HBV infection; and complete or ‘virologic’ cure – elimination of cccDNA, anti-HBs +ve and comparable with uninfected individual.
Newer antiviral treatments for HBV include anti cccDNA strategies. It is essential to target cccDNA since its persistence causes chronic hepatitis B and HBV cure can be achieved by elimination, suppression or control of cccDNA.
Methods for inhibiting cccDNA are: cytokines (IFN-a, LTb agonists); RNA targeting; epigenetic control; and cleavage enzymes.
Future regimen to achieve cure of HBV infection will require a combination of the existing and future therapies—nucleoside/nucleotide analogue (TDF, ETV); HBV gene expression inhibitor (si RNA: ARC-520); entry/capsid//secretion inhibitor (Myrcludex-B; HAP, PPA, REP-9AC); immune activator (TLR-7 agonist); as well as cccDNA inhibitor (CRISPR-Cas-9).

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