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Chronic hepatitis B: What should be the goal for new therapies?
Journal article   Open access   Peer reviewed

Chronic hepatitis B: What should be the goal for new therapies?

Timothy M. Block, Robert Gish, Haitao Guo, Anand Mehta, Andrea Cuconati, W. Thomas London and Ju-Tao Guo
Antiviral research, v 98(1), pp 27-34
01 Apr 2013
DOI: https://doi.org/10.1016/j.antiviral.2013.01.006
PMID: 23391846
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc3627746View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Life Sciences & Biomedicine Pharmacology & Pharmacy Science & Technology Virology
Chronic hepatitis B can currently be medically managed with either pegylated interferon-alpha (pegIFN-alpha.) or one of the five nucleos(t)ide analog Direct Acting Antivirals (DAAs) that inhibit the hepatitis B virus (HBV) DNA polymerase. While pegIFN-alpha is effective in approximately one-third of the treated patients, the polymerase inhibitors significantly reduce viral load in the vast majority of those treated. However, neither pegIFN-alpha nor nucleosi(t)de analogs are capable of reliably eliminating the virus and achieving a cure. Moreover, the interferons and polymerase inhibitors are recommended by US, European and Asian professional society practice guidelines for use in only a subset of those infected with HBV. This subset is the population with the greatest levels of circulating viral DNA and abnormal liver function. Although this is the population at the highest risk for cirrhosis and liver cancer, those who fall outside the treatment guidelines, with low levels of viral replication and normal serum ALTs, may also benefit from antiviral therapy. The questions are thus: are new classes of drugs needed to manage chronic hepatitis B? Is a cure possible? Is a cure even necessary? It is therefore important to define the meaning of a cure and determine what the goals of new therapies should be. In this article, we address those questions and propose two operational definitions of medically attainable cures. The first is a "functional cure" based on the clinical outcome, in which the patient's life expectancy becomes the same as that of an individual who has resolved his HBV infection without therapy. Because such an outcome cannot be measured over the short term, we also define an "apparent virological cure," based on the stable off-drug suppression of HBV viremia and antigenemia and the normalization of ALTs and other laboratory tests. We suggest that such a virological cure should be the goal of future therapeutics in all patients with chronic hepatitis B. The extent to which a virological cure predicts a functional cure will only be determined by long-term follow-up. (c) 2013 Elsevier B.V. All rights reserved.

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109 citations in Web of Science
115 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Pharmacology & Pharmacy
Virology
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