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New Approaches to the Treatment of Chronic Hepatitis B.

ABSTRACT: The currently recommended treatment for chronic hepatitis B virus (HBV) infection achieves only viral suppression whilst on therapy, but rarely hepatitis B surface antigen (HBsAg) loss. The ultimate therapeutic endpoint is the combination of HBsAg loss, inhibition of new hepatocyte infection, elimination of the covalently closed circular DNA (cccDNA) pool, and restoration of immune function in order to achieve virus control. This review concentrates on new antiviral drugs that target different stages of the HBV life cycle (direct acting antivirals) and others that enhance both innate and adaptive immunity against HBV (immunotherapy). Drugs that block HBV hepatocyte entry, compounds that silence or deplete the cccDNA pool, others that affect core assembly, agents that degrade RNase-H, interfering RNA molecules, and nucleic acid polymers are likely interventions in the viral life cycle. In the immunotherapy category, molecules that activate the innate immune response such as Toll-like-receptors, Retinoic acid Inducible Gene-1 (RIG-1) and stimulator of interferon genes (STING) agonists or checkpoint inhibitors, and modulation of the adaptive immunity by therapeutic vaccines, vector-based vaccines, or adoptive transfer of genetically-engineered T cells aim towards the restoration of T cell function. Future therapeutic trends would likely be a combination of one or more of the aforementioned drugs that target the viral life cycle and at least one immunomodulator.

SUBMITTER: Alexopoulou A

PROVIDER: S-EPMC7601587 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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New Approaches to the Treatment of Chronic Hepatitis B.

Alexopoulou Alexandra A Vasilieva Larisa L Karayiannis Peter P

Journal of clinical medicine 20201001 10

The currently recommended treatment for chronic hepatitis B virus (HBV) infection achieves only viral suppression whilst on therapy, but rarely hepatitis B surface antigen (HBsAg) loss. The ultimate therapeutic endpoint is the combination of HBsAg loss, inhibition of new hepatocyte infection, elimination of the covalently closed circular DNA (cccDNA) pool, and restoration of immune function in order to achieve virus control. This review concentrates on new antiviral drugs that target different s ...[more]

PMID: 33019573

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Project description:BACKGROUND:Chronic hepatitis C virus is difficult to treat and affects approximately 3 million Americans. Protease inhibitors increase the effectiveness of standard therapy, but they are costly. A genetic assay may identify patients most likely to benefit from this treatment advance. OBJECTIVE:To assess the cost-effectiveness of new protease inhibitors and an interleukin (IL)-28B genotyping assay for treating chronic hepatitis C virus. DESIGN:Decision-analytic Markov model. DATA SOURCES:Published literature and expert opinion. TARGET POPULATION:Treatment-naive patients with chronic, genotype 1 hepatitis C virus monoinfection. TIME HORIZON:Lifetime. PERSPECTIVE:Societal. INTERVENTION:Strategies are defined by the use of IL-28B genotyping and type of treatment (standard therapy [pegylated interferon with ribavirin]; triple therapy [standard therapy and a protease inhibitor]). Interleukin-28B-guided triple therapy stratifies patients with CC genotypes to standard therapy and those with non-CC types to triple therapy. OUTCOME MEASURES:Discounted costs (in 2010 U.S. dollars) and quality-adjusted life-years (QALYs); incremental cost-effectiveness ratios. RESULTS OF BASE-CASE ANALYSIS:For patients with mild and advanced fibrosis, universal triple therapy reduced the lifetime risk for hepatocellular carcinoma by 38% and 28%, respectively, and increased quality-adjusted life expectancy by 3% and 8%, respectively, compared with standard therapy. Gains from IL-28B-guided triple therapy were smaller. If the protease inhibitor costs $1100 per week, universal triple therapy costs $102,600 per QALY (mild fibrosis) or $51,500 per QALY (advanced fibrosis) compared with IL-28B-guided triple therapy and $70,100 per QALY (mild fibrosis) and $36,300 per QALY (advanced fibrosis) compared with standard therapy. RESULTS OF SENSITIVITY ANALYSIS:Results were sensitive to the cost of protease inhibitors and treatment adherence rates. LIMITATION:Data on the long-term comparative effectiveness of the new protease inhibitors are lacking. CONCLUSION:Both universal triple therapy and IL-28B-guided triple therapy are cost-effective when the least-expensive protease inhibitor are used for patients with advanced fibrosis. PRIMARY FUNDING SOURCE:Stanford University.

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New Approaches to the Treatment of Chronic Hepatitis B.

Publications

New Approaches to the Treatment of Chronic Hepatitis B.

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