Current treatment of hepatitis B

Dusheiko, G.; Antonakopoulos, Nikolas

doi:10.1136/gut.2005.077891

Cited by 26 publications

(34 citation statements)

References 166 publications

(126 reference statements)

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“…Currently, two major groups of antiviral reagents, interferon alpha (IFN-a) and nucleoside/tide analogs, are available for the treatment of HBV infection . IFN-a, an immunomodulator, can inhibit indirectly HBV replication by inducing the expression of endogenous antiviral proteins, leading to the remission of hepatitis in a highly selective population (Dusheiko and Antonakopoulos, 2008;Yuen et al, 2008). The nucleoside/tide analogs, such as lamivudine, adefovir, entecavir, and telbivudine, have been approved for the treatment of HBV infection, because they target the viral DNA polymerase, leading to the inhibition of viral replication.…”

Section: Introductionmentioning

confidence: 99%

“…Although those available anti-HBV drugs have improved the life quality of patients with HBV infection, long-term treatments with those reagents often result in the development of drug resistance in many patients with HBV infection (Chang and Lai, 2006;Delaney et al, 2002;Feld et al, 2007;Lai et al, 2007). Prolonged treatment with lamivudine for 1 year or more resulted in the emergence of lamivudine-resistant HBV mutants in 17-46% of patients (Dusheiko and Antonakopoulos, 2008;Gaillard et al, 2002). Therefore, the discovery and development of new anti-HBV therapeutic reagents will be of great significance.…”

Section: Introductionmentioning

confidence: 99%

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Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

Niu

Ding

et al. 2011

Med Chem Res

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Nucleoside/tide analogs are now widely used for treatment of chronic hepatitis B (CHB). However, available nucleoside/tide analogs for treatment of CHB usually have limited therapeutic effect and potential adverse effects on CHB patients. We evaluated the anti-HBV effects of three novel derivatives (compounds 1, 4, and 8) of adefovir on the replication of hepatitis B virus (HBV) and determined their cytotoxicity. The effects of those compounds on the replication of human HBV in the HepG2 2.2.15 cell line and duck HBV in infected ducks were characterized by measuring the extracellular and intracellular HBV DNA using the quantitative real-time PCR and Southern blot assays. Their cytotoxicities against HepG2 cells were evaluated by MTT and measuring the contents of mitochondrial DNA using the dot blot assay. We found that all of the compounds inhibited the production of HBV in a dose-dependent manner, similar to that of adefovir dipivoxil. Furthermore, treatment with any of the compounds reduced significantly the replication of DHBV in ducks, accompanied by a significant reduction of inflammation in the livers, and the compound 1 appeared to be a fast-acting and long-lasting anti-DHBV reagent. Importantly, all of the compounds showed little cytotoxicity against HepG2 cells, even at a concentration of 1 mM. Collectively, those novel derivatives of adefovir had potent anti-HBV activity with little adverse effect and may be therapeutic candidates for potential clinical studies.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antiviral effects of three novel derivatives of adefovir on the replication of hepatitis B virus

Niu

Ding

et al. 2011

Med Chem Res

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“…However, clinical trials and cohort studies have shown that resistance to LAM develops rapidly, with around 70% of patients harbouring LAM-resistant YMDD mutant viral strains after 5 years of treatment (1,2). This can have serious clinical consequences because the virological breakthrough that follows the development of LAM resistance is associated with a severe, acute and sometimes fatal exacerbation of liver disease (3,4).…”

Section: Introductionmentioning

confidence: 99%

Avoiding and managing lamivudine resistance in chronic hepatitis B: current approaches and potential strategies including pegylated interferon

Marcellin

Sung

Piratvisuth

2010

Liver International

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Since its approval for the treatment of chronic hepatitis B in 1998, lamivudine (LAM) has been used extensively throughout the world, because of its relatively low costs and favourable tolerability. However, clinical trials and cohort studies have demonstrated that a high rate of resistance to this drug develops and, as a result, it is no longer included as a first-line therapy in most current treatment guidelines. Nevertheless, because of its low cost, this drug continues to be used in many countries and the pool of patients who have developed resistance to LAM continues to increase. Thus, there is a clear need to develop coherent management strategies to treat such patients as well as limit the emergence of resistance in the first instance. The purpose of this review is to highlight the need to aim for long-term treatment success while limiting the emergence of drug resistance and its consequences for the future. In addition to add-on/switch strategies with other nucleos(t)ide analogs, currently available data suggest that interferon-based therapies, with their potential to induce a sustained response, are worthy of consideration not only for reducing de novo resistance but as an option for the management of those patients in whom drug resistance has already developed.

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“…Liver biopsy remains an impractical and expensive diagnostic tool in resource-constrained areas. Current guidelines, such as the European Association for the Study of the Liver (EASL) guidelines, will need constant and rapid adjustment as new therapies and information become available [6,7].…”

Section: Indications For Treatment Of Hepatitis Bmentioning

confidence: 99%