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- Title
Hepatitis B cure: How and when.
- Authors
Dusheiko, Geoffrey; Valenti, Luca
- Abstract
Background: First‐ and second‐ generation new treatments are being evaluated to provide a cure for hepatitis B. The life cycle of HBV includes several well‐ categorized steps that are targets for new treatments. A cure remains a major challenge even if it is measured by HBsAg seroclearance alone. The notion of a functional cure of hepatitis B has been accepted, while a partial functional cure has been more tentatively defined as a decline in HBsAg concentrations to lower levels after finite treatment. Methods: More profound suppression of hepatitis B replication through the addition of capsid inhibitors with nucleoside analogues could improve patient prognosis and a sustained treatment response. Several strategies are being evaluated to achieve a cure: (a) deepening inhibition of HBV replication or (b) a reduction in HBsAg presentation for HBsAg seroclearance. Results: Fortunately, there are signs of important progress in the treatment of hepatitis B including improved on‐ treatment reductions or seroclearance of HBsAg in phase 2 studies that was not achieved with chain terminators and inhibitors of initiation of DNA synthesis. Progress in immunomodulatory therapy has lagged behind that of antiviral therapy. Conclusions: Increasing the multilayered impaired and dysfunctional immune response in hepatitis B is perhaps more likely and feasible after a reduction in host antigen burden. Other potential experimental strategies include CRISPR‐ Cas9 genome‐ editing nucleases to specifically target and cleave cccDNA or novel monoclonal antibodies.
- Subjects
HEPATITIS B; CHRONIC hepatitis B; DNA synthesis; MONOCLONAL antibodies; NUCLEASES; PROGNOSIS
- Publication
Liver International, 2021, Vol 41, p24
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.14837