Article: Treatment of chronic hepatitis B: Evolution over two decades
| Title | Treatment of chronic hepatitis B: Evolution over two decades | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Authors | Yuen, MF1 Lai, CL1 | ||||||||
| Keywords | Antiviral agents Chronic hepatitis B HBV DNA Nucleoside analogs Treatment | ||||||||
| Issue Date | 2011 | ||||||||
| Publisher | Wiley-Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JGH | ||||||||
| Citation | Journal Of Gastroenterology And Hepatology, 2011, v. 26 SUPPL. 1, p. 138-143 [How to Cite?] DOI: http://dx.doi.org/10.1111/j.1440-1746.2010.06545.x | ||||||||
| Abstract | There has been a recent paradigm shift in the indications and endpoints of treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)-negative disease is being increasingly recognized. Antiviral treatment for both HBeAg-positive and HBeAg-negative patients should aim at long-term suppression of HBV DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg) seroconversion. Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α. HBeAg seroconversion using pegylated IFN-α is 33%, with only 25% of HBeAg-positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg-negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infection. With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd. | ||||||||
| ISSN | 0815-9319 2011 Impact Factor: 2.865 2011 SCImago Journal Rankings: 0.208 | ||||||||
| DOI | http://dx.doi.org/10.1111/j.1440-1746.2010.06545.x | ||||||||
| ISI Accession Number ID | WOS:000285880400018
Funding Information: MF Yuen acted as consultant and received research grants from Glaxo Smith Kline, Gristol Myers Squibb and Novertis. CL Lai has acted as consultant for Bristol Myers Squibb and Gilead Sciences. | ||||||||
| References | References in Scopus |
| dc.contributor.author | Yuen, MF | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Lai, CL | ||||||||
| dc.date.accessioned | 2011-09-23T05:50:30Z | ||||||||
| dc.date.available | 2011-09-23T05:50:30Z | ||||||||
| dc.date.issued | 2011 | ||||||||
| dc.description.abstract | There has been a recent paradigm shift in the indications and endpoints of treatment for chronic hepatitis B (CHB). Hepatitis B e antigen (HBeAg)-negative disease is being increasingly recognized. Antiviral treatment for both HBeAg-positive and HBeAg-negative patients should aim at long-term suppression of HBV DNA, with the ultimate ideal endpoint of hepatitis B surface antigen (HBsAg) seroconversion. Conventional interferon alpha (IFN-α), the only agent licensed in 1991, has been superseded by pegylated IFN-α. HBeAg seroconversion using pegylated IFN-α is 33%, with only 25% of HBeAg-positive patients achieving undetectable HBV DNA by polymerase chain reaction (PCR) assay. Five nucleoside/nucleotide analogues have been licensed since 1998. Lamivudine, an L-nucleoside, is limited by the development of resistance in 76% of patients after 5 years of therapy. Telbivudine, another L-nucleoside, is more potent than lamivudine but resistance still develops in 25% of HBeAg-positive and 11% HBeAg-negative patients after 2 years. Adefovir, an acyclic phosphonate, is relatively weak, but is effective against lamivudine- and telbivudine- resistant mutations, for which it should be used in combination (add-on therapy) rather than substituted. Resistance to adefovir develops slowly, rising to 29% for HBeAg-negative patients by year 5, but more rapidly when used alone for lamivudine-resistant HBV. Currently the two first line nucleoside/nucleotides are entecavir and tenofovir. Entecavir, a cyclopentane (D-nucleoside), is very potent, with 94% of patients having undetectable HBV DNA after 5 years. Resistance develops in only 1.2% of treatment-naïve patients. Tenofovir, another acyclic nucleotide, is more potent with less renal toxicity compared to adefovir. It is effective against lamivudine-resistant mutations when used alone. No resistance to tenofovir has been described after its use for 3 years or longer, often for patients with human immunodeficiency virus/HBV co-infection. With these current, potent antiviral agents associated with very low rates of resistance, long-term HBV DNA suppression and possibly even reversal of cirrhosis can now be achieved in a proportion of patients. In addition, long-term treatment with these antiviral agents is associated with a reduced risk of development of hepatocellular carcinoma. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd. | ||||||||
| dc.description.nature | link_to_OA_fulltext | ||||||||
| dc.identifier.citation | Journal Of Gastroenterology And Hepatology, 2011, v. 26 SUPPL. 1, p. 138-143 [How to Cite?] DOI: http://dx.doi.org/10.1111/j.1440-1746.2010.06545.x | ||||||||
| dc.identifier.doi | http://dx.doi.org/10.1111/j.1440-1746.2010.06545.x | ||||||||
| dc.identifier.epage | 143 | ||||||||
| dc.identifier.hkuros | 195204 | ||||||||
| dc.identifier.hkuros | 189893 | ||||||||
| dc.identifier.isi | WOS:000285880400018
Funding Information: MF Yuen acted as consultant and received research grants from Glaxo Smith Kline, Gristol Myers Squibb and Novertis. CL Lai has acted as consultant for Bristol Myers Squibb and Gilead Sciences. | ||||||||
| dc.identifier.issn | 0815-9319 2011 Impact Factor: 2.865 2011 SCImago Journal Rankings: 0.208 | ||||||||
| dc.identifier.issue | SUPPL. 1 | ||||||||
| dc.identifier.pmid | 21199525 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-78650780786 | ||||||||
| dc.identifier.spage | 138 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/139477 | ||||||||
| dc.identifier.volume | 26 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | Wiley-Blackwell Publishing Asia. The Journal's web site is located at http://www.blackwellpublishing.com/journals/JGH | ||||||||
| dc.publisher.place | Australia | ||||||||
| dc.relation.ispartof | Journal of Gastroenterology and Hepatology | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.rights | The definitive version is available at www3.interscience.wiley.com | ||||||||
| dc.subject.mesh | Antiviral Agents - therapeutic use | ||||||||
| dc.subject.mesh | Carcinoma, Hepatocellular - prevention and control - virology | ||||||||
| dc.subject.mesh | Hepatitis B virus - genetics - immunology - pathogenicity | ||||||||
| dc.subject.mesh | Hepatitis B, Chronic - complications - diagnosis - drug therapy | ||||||||
| dc.subject.mesh | Liver Neoplasms - prevention and control - virology | ||||||||
| dc.subject | Antiviral agents | ||||||||
| dc.subject | Chronic hepatitis B | ||||||||
| dc.subject | HBV DNA | ||||||||
| dc.subject | Nucleoside analogs | ||||||||
| dc.subject | Treatment | ||||||||
| dc.title | Treatment of chronic hepatitis B: Evolution over two decades | ||||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong