Entecavir: A new treatment option for chronic hepatitis B

Zoulim, Fabien

doi:10.1016/j.jcv.2006.01.010

Cited by 33 publications

(30 citation statements)

References 32 publications

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“…Entecavir was evaluated in phase II trials (Lai et al, 2002;Wolters et al, 2002) and in 3 controlled phase III trials involving 1633 patients with chronic HBV infection, detectable HBV DNA, persistently elevated ALT levels and chronic inflammation on liver biopsy. In 2 randomized studies involving nucleoside naive patients (HBeAg positive or negative), entecavir administered 0.5 mg orally once daily for 52 weeks was superior to lamivudine (100 mg orally once daily for 52 weeks) on the primary efficacy endpoint of histological improvement and on secondary endpoints, such as the reduction in viral load and normalization of ALT Lai et al, 2006;Zoulim, 2006). After two years of treatment, 81% of patients receiving entecavir had a viral load below 300 copies / mL versus only 39% of patients receiving lamivudine, 31% seronconverted to anti-HBe versus 26% in the lamivudine group, and 5% showed a clearance of HBsAg versus 3% in lamivudine treated patients (Gish et al, 2005a).…”

Section: Results Of Adefovir Dipivoxil Administrationmentioning

confidence: 99%

Antiviral therapy of chronic hepatitis B

Zoulim

2006

Antiviral Research

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Treatment of chronic hepatitis B remains a clinical challenge. Long-term viral suppression is a major goal of antiviral therapy to improve the clinical outcome of the patients. Antiviral treatment of chronic hepatitis B relies currently on immune modulators such as interferon alpha and its pegylated form, and viral polymerase inhibitors. Because of the slow kinetics of viral clearance and the spontaneous viral genome variability, viral mutants resistant to nucleoside analogs may be selected. However, the development of new antiviral agents is rapidly improving the offing of therapy of chronic hepatitis B. These new therapeutic advances are reviewed in this manuscript.3

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Section: Results Of Adefovir Dipivoxil Administrationmentioning

confidence: 99%

Antiviral therapy of chronic hepatitis B

Zoulim

2006

Antiviral Research

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“…This could explain the apparent, though probably less than complete [29] , disappearance of cccDNA during spontaneous clearance of HBV infection. However, therapeutic cccDNA elimination from the chronically infected liver remains a major issue even with the latest generation antivirals [30,31] ; further investigations into the mechanism of cccDNA formation, and possibly breakdown, are clearly warranted.…”

Section: Hepatitis B Virus Replicationmentioning

confidence: 99%

Hepatitis B virus replication

Beck

Nassal

2007

WJG

413

382

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Hepadnaviruses, including human hepatitis B virus (HBV), replicate through reverse transcription of an RNA intermediate, the pregenomic RNA (pgRNA). Despite this kinship to retroviruses, there are fundamental differences beyond the fact that hepadnavirions contain DNA instead of RNA. Most peculiar is the initiation of reverse transcription: it occurs by protein-priming, is strictly committed to using an RNA hairpin on the pgRNA, ε, as template, and depends on cellular chaperones; moreover, proper replication can apparently occur only in the specialized environment of intact nucleocapsids. This complexity has hampered an in-depth mechanistic understanding. The recent successful reconstitution in the test tube of active replication initiation complexes from purified components, for duck HBV (DHBV), now allows for the analysis of the biochemistry of hepadnaviral replication at the molecular level. Here we review the current state of knowledge at all steps of the hepadnaviral genome replication cycle, with emphasis on new insights that turned up by the use of such cellfree systems. At this time, they can, unfortunately, not be complemented by three-dimensional structural information on the involved components. However, at least for the ε RNA element such information is emerging, raising expectations that combining biophysics with biochemistry and genetics will soon provide a powerful integrated approach for solving the many outstanding questions. The ultimate, though most challenging goal, will be to visualize the hepadnaviral reverse transcriptase in the act of synthesizing DNA, which will also have strong implications for drug development.© 2007 The WJG Press. All rights reserved. Dieter Glebe, PhD, Series EditorPO Box 2345, Beijing 100023, China World J Gastroenterol 2007 January 7; 13(1): 48-64 www.wjgnet.com World Journal of Gastroenterology ISSN 1007-9327 wjg@wjgnet.com © 2007 OVERVIEW OVER THE HEPADNAVIRAL GENOME REPLICATION CYCLEReplication of the hepadnaviral genome can broadly be divided into three phases ( Figure 1): (1) Infectious virions contain in their inner icosahedral core the genome as a partially double-stranded, circular but not covalently closed DNA of about 3.2 kb in length (relaxed circular, or RC-DNA); (2) upon infection, the RC-DNA is converted, inside the host cell nucleus, into a plasmid-like covalently closed circular DNA (cccDNA); (3) from the cccDNA, several genomic and subgenomic RNAs are transcribed by cellular RNA polymerase Ⅱ; of these, the pregenomic RNA (pgRNA) is selectively packaged into progeny capsids and is reverse transcribed by the co-packaged P protein into new RC-DNA genomes. Matured RC-DNA containing-but not immature RNA containingnucleocapsids can be used for intracellular cccDNA amplification, or be enveloped and released from the cell as progeny virions. Below we discuss these genome conversions, with emphasis on the reverse transcription step, and particularly its unique initiation mechanism. RC-DNA TO cccDNA CONVERSIONPersistent viral infections require tha...

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“…It is safe and has a very low resistance rate among treatment-naïve patients as compared to relatively high rate in lamivudine-resistant patients and so warrant consideration for first-line therapy. However, it is much more costly, and the cost-effective analysis need to be systematically assessed [110,111]. After initial data on the lack of activity against HIV, it is recently reported that it affects HIV-1 replication and resistance [112].…”

Section: Entecavir Therapy In Other Patient Subgroupsmentioning

confidence: 99%

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

Leung

2008

Hepatol Int

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Forty years ago in 1967, Professor Blumberg discovered the Australian Antigen, later known as the hepatitis B surface antigen, and was awarded the Nobel Prize. This discovery enables the diagnosis of hepatitis B virus (HBV) infection and defines its epidemiology. Viral hepatitis B infection affects global health situation, and chronic hepatitis B (CHB) is particularly serious in the Asia-Pacific region. HBV vaccines created the first breakthrough in HBV prevention. Through universal HBV vaccination program for the newborns, promoted since the mid-1980s, the main route that perpetuates chronic infection from mother to child is curbed. Most children and young adults now have immunity against HBV infection. The next breakthrough comes with therapy for CHB. This prevents progression to cirrhosis and hepatocellular carcinoma. Standard interferon therapy with modest efficacy has been largely replaced by therapy with nuclos(t)ide analogues or pegylated interferons alfa-2a and -2b. Lamivudine was approved by the FDA USA in 1998, followed by adefovir dipivoxil in 2002, entecavir in 2005, and telbivudine in 2006. Clevudine, tenofovir, and many promising candidates are in different stages of development and clinical trial. This paper critically reviews recent data published or presented since the APASL Consensus and Guideline Update of 2005. Clinical efficacy mostly in patients with raised serum alanine aminotransferase will be analyzed.

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Entecavir: A new treatment option for chronic hepatitis B

Cited by 33 publications

References 32 publications

Antiviral therapy of chronic hepatitis B

Antiviral therapy of chronic hepatitis B

Hepatitis B virus replication

Recent data on treatment of chronic hepatitis B with nucleos(t)ide analogues

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