Treatment of chronic hepatitis B: Evolution over two decades

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2010.06545.x/full

Treatment of chronic hepatitis B: Evolution over two decades

Man-Fung Yuen, Ching-Lung Lai

Article first published online: 4 JAN 2011

DOI: 10.1111/j.1440-1746.2010.06545.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Special Issue: Silver Jubilee Supplement: Celebrating 25 years of JGH

Volume 26, Issue Supplement s1, pages 138–143, January 2011

Additional Information(Show All)

How to CiteAuthor InformationPublication History

How to Cite

Yuen, M.-F. and Lai, C.-L. (2011), Treatment of chronic hepatitis B: Evolution

over two decades. Journal of Gastroenterology and Hepatology, 26: 138–143.

doi: 10.1111/j.1440-1746.2010.06545.x

Author Information

Department of Medicine, the University of Hong Kong, Queen Hospital, Hong

Kong, China

*Correspondence: Professor Man-Fung Yuen and Ching-Lung Lai, Department of

Medicine, The University of Hong Kong, Queen Hospital, Pokfulam Road, Hong

Kong, China. Email: mfyuen@... or hrmelcl@...

Conflict of interest MF Yuen acted as consultant and received research grants

from Glaxo Kline, Gristol Myers Squibb and Novertis. CL Lai has acted as

consultant for Bristol Myers Squibb and Gilead Sciences.

Publication History

Issue published online: 4 JAN 2011

Article first published online: 4 JAN 2011

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licensed in 1991, has been superseded by pegylated IFN-α.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.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1111/j.1440-1746.2010.06545.x/full

Treatment of chronic hepatitis B: Evolution over two decades

Man-Fung Yuen, Ching-Lung Lai

Article first published online: 4 JAN 2011

DOI: 10.1111/j.1440-1746.2010.06545.x

© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell

Publishing Asia Pty Ltd

Issue

Journal of Gastroenterology and Hepatology

Special Issue: Silver Jubilee Supplement: Celebrating 25 years of JGH

Volume 26, Issue Supplement s1, pages 138–143, January 2011

Additional Information(Show All)

How to CiteAuthor InformationPublication History

How to Cite

Yuen, M.-F. and Lai, C.-L. (2011), Treatment of chronic hepatitis B: Evolution

over two decades. Journal of Gastroenterology and Hepatology, 26: 138–143.

doi: 10.1111/j.1440-1746.2010.06545.x

Author Information

Department of Medicine, the University of Hong Kong, Queen Hospital, Hong

Kong, China

*Correspondence: Professor Man-Fung Yuen and Ching-Lung Lai, Department of

Medicine, The University of Hong Kong, Queen Hospital, Pokfulam Road, Hong

Kong, China. Email: mfyuen@... or hrmelcl@...

Conflict of interest MF Yuen acted as consultant and received research grants

from Glaxo Kline, Gristol Myers Squibb and Novertis. CL Lai has acted as

consultant for Bristol Myers Squibb and Gilead Sciences.

Publication History

Issue published online: 4 JAN 2011

Article first published online: 4 JAN 2011

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.