What Is the Best End Point for Hepatitis B Treatment?

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> http://www.annals.org/cgi/content/full/148/7/560-a> > What Is the Best End

Point for Hepatitis B Treatment?> > > Bulent Degertekin, MD, and S.F. Lok,

MD> > 1 April 2008 | Volume 148 Issue 7 | Pages 560-561> > > IN RESPONSE:> > We

appreciate Drs. Lai and Yuen's comments. We agree that lifelong > maintenance

therapy would be preferred when safe, affordable, and > effective treatment is

available to prevent disease recurrence. > However, the safety of lifetime use

of nucleoside or nucleotide > analogues for hepatitis B has not been

established. Adefovir is > associated with a small risk for nephrotoxicity.

Entecavir at high > doses in rodents was associated with a variety of tumors,

prompting > the manufacturer to pledge a 10-year follow-up study to establish

its > long-term safety in humans. Furthermore, currently available > hepatitis B

treatments are very expensive, and their efficacy in > maintaining viral

suppression is diminished by the selection of > drug-resistant mutations during

long-term therapy. Even in cancer > that has the propensity for late recurrence,

treatment is > discontinued after disease remission or a finite duration of >

consolidation therapy (1).> > We completely agree that cirrhosis and

hepatocellular carcinoma are > the key outcomes of chronic HBV infection.

However, as Drs. Lai and > Yuen indicated, a persistently high HBV DNA level is

the most > important predictor of these outcomes. Thus, the risk for adverse >

outcomes after treatment discontinuation is related to the risk for >

reactivation of viral replication.> > Drs. Lai and Yuen cited a recent study (2)

in Greek children showing > that 21 of 34 Thracian Muslims (62%) had an

HBV-infected mother. > However, this study did not determine whether the mothers

were the > source of infection and whether the infection was acquired >

perinatally. In the same study, only 47 of 121 Thracian Christians > (39%) had

an HBV-infected mother. Other studies from Italy and > Greece, where HBV

genotype D is preponderant, reported increased > prevalence of chronic HBV

infection with age, with the highest > prevalence in those older than 40 years

of age. This supports the > idea that HBV infection in these countries is mostly

acquired during > childhood and adult life (3, 4).> > Although the strict

definition of HBeAg seroconversion was not > clearly described in the 2007

American Association for the Study of > Liver Diseases Practice Guidelines (5),

a recent analysis of 74 > patients who lost HBeAg after 48 weeks of entecavir

therapy found > that 70 had HBeAg seroconversion, 71 had undetectable HBV DNA by

> polymerase chain reaction, and 63 had normalization of > aminotransferases.

These findings support the idea that most patients > who achieve HBeAg

seroconversion during nucleoside or nucleotide > analogue therapy meet the

strict definition of HBeAg seroconversion (6).> From the University of Michigan

Health System, Ann Arbor, MI 48109.> > Potential Financial Conflicts of

Interest: None disclosed.> References> > 1. Fisher B, Dignam J, J,

Wolmark N. Five versus more than > five years of tamoxifen for lymph

node-negative breast cancer: > updated findings from the National Surgical

Adjuvant Breast and Bowel > Project B-14 randomized trial. J Natl Cancer Inst.

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11333290].<http://www.annals.org/cgi/content/full/148/7//cgi/ijlink?linkType=ABS\

T & journalCode=jnci & resid=93/9/684>[Abstract/Free<http://www.annals.org/cgi/conte\

nt/full/148/7//cgi/ijlink?linkType=ABST & journalCode=jnci & resid=93/9/684> > Full

Text]> > 2. Zacharakis G, Koskinas J, Kotsiou S, Pouliou E, Papoutselis M, >

Tzara F, et al. Natural history of chronic hepatitis B virus > infection in

children of different ethnic origins: a cohort study > with up to 12 years'

follow-up in northern Greece. J Pediatr > Gastroenterol Nutr. 2007;44:84-91.

[PMID: >

17204959].<http://www.annals.org/cgi/content/full/148/7//cgi/external_ref?access\

_num=17204959 & link_type=MED>[Medline] > > > 3. Stroffolini T, Guadagnino V,

Chionne P, Procopio B, Mazzuca EG, > Quintieri F, et al. A population based

survey of hepatitis B virus > infection in a southern Italian town. Ital J

Gastroenterol Hepatol. > 1997;29:415-8. [PMID: >

9494849].<http://www.annals.org/cgi/content/full/148/7//cgi/external_ref?access_\

num=9494849 & link_type=MED>[Medline] > > > 4. Sypsa V, Hadjipaschali E, Hatzakis

A. Prevalence, risk factors and > evaluation of a screening strategy for chronic

hepatitis C and B > virus infections in healthy company employees. Eur J

Epidemiol. > 2001;17:721-8. [PMID: >

12086089].<http://www.annals.org/cgi/content/full/148/7//cgi/external_ref?access\

_num=12086089 & link_type=MED>[Medline] > > > 5. Lok AS, McMahon BJ. Chronic

hepatitis B. Hepatology. > 2007;45:507-39. [PMID: >

17256718].<http://www.annals.org/cgi/content/full/148/7//cgi/external_ref?access\

_num=17256718 & link_type=MED>[Medline] > > > 6. Gish RG, Lok AS, Chang TT, de Man

RA, Gadano A, Sollano J, et al. > Entecavir therapy for up to 96 weeks in

patients with HBeAg-positive > chronic hepatitis B. Gastroenterology.

2007;133:1437-44. [PMID: >

17983800].<http://www.annals.org/cgi/content/full/148/7//cgi/external_ref?access\

_num=17983800 & link_type=MED>[Medline] > > > > Related articles in ls:

Perspectives The Natural History and > Treatment of Chronic Hepatitis B: A

Critical Evaluation of Standard > Treatment Criteria and End PointsChing-Lung

Lai AND Man-Fung Yuen> ls 2007 147: 58-61. >

<http://www.annals.org/cgi/content/full/148/7//cgi/content/abstract/147/1/58>[AB\

STRACT]<http://www.annals.org/cgi/content/full/148/7//cgi/content/full/147/1/58>\

[Full > Text]> > Letters What Is the Best End Point for Hepatitis B >

Treatment?Ching-Lung Lai AND Man-Fung Yuen> ls 2008 148: 560. >

<http://www.annals.org/cgi/content/full/148/7//cgi/content/full/148/7/560>[Full

> Text]> > >

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