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The Molecular and Structural Basis of HBV-resistance to Nucleos(t)ide Analogs.

Gupta N, Goyal M, Wu CH, Wu GY - J Clin Transl Hepatol (2014)

Bottom Line: The main problems with this therapy are the frequency and severity of side effects.In contrast, nucleos(t)ide analogs (NAs) have significantly lower side effects, but require long term treatment as sustained virological response rates are extremely low.Only by understanding the molecular basis of resistance and using agents with multiple sites of action can drugs be designed to optimally prevent the occurrence of HBV antiviral resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Heath Center, Farmington, USA.

ABSTRACT
Infection with hepatitis B virus (HBV) is a worldwide health problem. Chronic hepatitis B can lead to fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Management of the latter two conditions often requires liver transplantation. Treatment with conventional interferon or pegylated interferon alpha can clear the virus, but the rates are very low. The likelihood, however, of viral resistance to interferon is minimal. The main problems with this therapy are the frequency and severity of side effects. In contrast, nucleos(t)ide analogs (NAs) have significantly lower side effects, but require long term treatment as sustained virological response rates are extremely low. However, long term treatment with NAs increases the risk for the development of anti-viral drug resistance. Only by understanding the molecular basis of resistance and using agents with multiple sites of action can drugs be designed to optimally prevent the occurrence of HBV antiviral resistance.

No MeSH data available.


Related in: MedlinePlus

Molecular structures of approved NAs.
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f03: Molecular structures of approved NAs.

Mentions: The presence of extremely stable cccDNA HBV in infected hepatocytes is the major obstacle to permanent elimination of HBV.77,78 The cccDNA acts as template for viral RNA genome production. The DNA-dependent DNA polymerase of HBV catalyzes synthesis of RNA, RNase H, and protein priming activities along with replication of HBV genome. Recently, NAs have been developed to directly inhibit the function of HBV DNA polymerase by either competitive binding to the enzyme or by terminating viral replication prematurely, which inhibits viral genome production. NAs currently available for HBV treatment are shown in Fig. 3.


The Molecular and Structural Basis of HBV-resistance to Nucleos(t)ide Analogs.

Gupta N, Goyal M, Wu CH, Wu GY - J Clin Transl Hepatol (2014)

Molecular structures of approved NAs.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4548360&req=5

f03: Molecular structures of approved NAs.
Mentions: The presence of extremely stable cccDNA HBV in infected hepatocytes is the major obstacle to permanent elimination of HBV.77,78 The cccDNA acts as template for viral RNA genome production. The DNA-dependent DNA polymerase of HBV catalyzes synthesis of RNA, RNase H, and protein priming activities along with replication of HBV genome. Recently, NAs have been developed to directly inhibit the function of HBV DNA polymerase by either competitive binding to the enzyme or by terminating viral replication prematurely, which inhibits viral genome production. NAs currently available for HBV treatment are shown in Fig. 3.

Bottom Line: The main problems with this therapy are the frequency and severity of side effects.In contrast, nucleos(t)ide analogs (NAs) have significantly lower side effects, but require long term treatment as sustained virological response rates are extremely low.Only by understanding the molecular basis of resistance and using agents with multiple sites of action can drugs be designed to optimally prevent the occurrence of HBV antiviral resistance.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Heath Center, Farmington, USA.

ABSTRACT
Infection with hepatitis B virus (HBV) is a worldwide health problem. Chronic hepatitis B can lead to fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Management of the latter two conditions often requires liver transplantation. Treatment with conventional interferon or pegylated interferon alpha can clear the virus, but the rates are very low. The likelihood, however, of viral resistance to interferon is minimal. The main problems with this therapy are the frequency and severity of side effects. In contrast, nucleos(t)ide analogs (NAs) have significantly lower side effects, but require long term treatment as sustained virological response rates are extremely low. However, long term treatment with NAs increases the risk for the development of anti-viral drug resistance. Only by understanding the molecular basis of resistance and using agents with multiple sites of action can drugs be designed to optimally prevent the occurrence of HBV antiviral resistance.

No MeSH data available.


Related in: MedlinePlus