Molecular mechanisms of resistance to antiviral therapy in patients with chronic hepatitis B.

Abstract:

:Similar to the human immunodeficiency virus (HIV), the hepatitis B virus (HBV) replicates via reverse transcription, in this case, within infected hepatocytes. Substantial advances have been achieved in the past ten years in developing and utilizing nucleoside/nucleotide analog drugs to inhibit HBV replication. Most are chain terminators that interfere with one or more steps in the replication cycle. Four of them (lamivudine, adefovir dipivoxil, entecavir, and telbivudine), have been approved by the United States Food and Drug Administration (FDA) for the treatment of chronic hepatitis B (CHB). In clinical trials of HBeAg positive and negative CHB patients, 48-52 week of treatment with these drugs can induce a 4-7 log decrease of HBV viremia and histological improvement. Long-term suppression of active HBV replication has been found to be associated with decreased inflammation, reversal of liver fibrosis and a lower incidence of hepatocellular carcinoma. However, permanent clearance of HBV is rarely achieved with current available antiviral agents, maintenance therapy being required for continuous suppression of HBV replication. In patients on continuous therapy, drug resistant mutations develop with all four drugs. Combination therapy with different nucleos(t)ide analog drugs or nucleos(t)ide drugs and pegylated interferon needs further clinical study. Newer promising nucleotide analog drugs with more potent antiviral efficacy are also under development.

journal_name

Curr Mol Med

authors

Yuan HJ,Lee WM

doi

10.2174/156652407780059159

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

185-97

issue

2

eissn

1566-5240

issn

1875-5666

journal_volume

7

pub_type

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