Use of Tumor Necrosis Factor-á Inhibitors in Patients with Chronic Hepatitis B Infection

[Guest guest]

Use of Tumor Necrosis Factor-á Inhibitors in Patients with Chronic Hepatitis B

Infection

B. Carroll MD, FACP, a, and I. Bond DOa

aSan Uniformed Services Health Education Consortium (SAUSHEC), Wilford

Hall Medical Center, Lackland Air Force Base, Lackland, Texas

Available online 25 January 2008.

Objective

Tumor necrosis factor-á (TNF-á) inhibitors have emerged as a potent treatment

for rheumatoid arthritis (RA), but not without significant risks. In chronic

hepatitis B viral infection TNF-á is readily produced, and viral clearance is

dependent on the amount bioavailable. Limited data suggest that TNF-á inhibitors

may facilitate uncontrolled hepatitis B viral replication. The purpose of this

article was to provide a detailed review of the role of TNF-á in controlling

hepatitis B viral infection and the clinical impact blockade might have on viral

control.

Methods

We describe a patient with chronic hepatitis B viral infection and RA treated

with etanercept. We then review case reports, expert opinion, and manufacturer

recommendations regarding hepatitis B viral infection, TNF-á, and TNF-á

inhibitors.

Results

To date, 13 patients with chronic hepatitis B infection treated with TNF-á

inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some

patients received antiviral therapy for hepatitis B (specifically lamivudine)

before, during, or after TNF-á inhibitors were started. Clinically apparent

reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose

of infliximab. Etanercept was not associated with a similar reactivation. The

difference between infliximab and etanercept in viral reactivation may be linked

to the pharmacologic difference of each medication.

Conclusions

TNF-á inhibitors in general should be used cautiously in chronic hepatitis B

viral infection. But if necessary, when deciding which agent to use, the

clinician should consider the mechanism by which the body clears TNF-á.

Keywords: tumor necrosis factor alpha; hepatitis B; etanercept; infliximab;

adalimumab

The authors received neither financial support nor had any affiliation with

organizations outside of their respective institutions. Dr. Carroll is a

shareholder of Abbott Pharmaceuticals (adalimumab-Humira R), Amgen/Wyeth

(etanercept-Enbrel R), and Gilead Sciences (adefovir dipivoxil-Hepsera R).

Address reprint requests to B. Carroll, MD, FACP, 301 Fisher Street,

Keesler AFB, MS 39564

Note to users: The section " Articles in Press " contains peer reviewed accepted

articles to be published in this journal. When the final article is assigned to

an issue of the journal, the " Article in Press " version will be removed from

this section and will appear in the associated published journal issue. The date

it was first made available online will be carried over. Please be aware that

although " Articles in Press " do not have all bibliographic details available

yet, they can already be cited using the year of online publication and the DOI

as follows: Author(s), Article Title, Journal (Year), DOI. Please consult the

journal's reference style for the exact appearance of these elements,

abbreviation of journal names and the use of punctuation.

There are three types of " Articles in Press " :

Accepted manuscripts: these are articles that have been peer reviewed and

accepted for publication by the Editorial Board. The articles have not yet been

copy edited and/or formatted in the journal house style.

Uncorrected proofs: these are copy edited and formatted articles that are not

yet finalized and that will be corrected by the authors. Therefore the text

could change before final publication.

Corrected proofs: these are articles containing the authors' corrections and

may, or may not yet have specific issue and page numbers assigned.

Seminars in Arthritis and Rheumatism

Article in Press, Corrected Proof

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b2756af49fcb467bffdcb1e1efece340

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!

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[Guest guest]

Use of Tumor Necrosis Factor-á Inhibitors in Patients with Chronic Hepatitis B

Infection

B. Carroll MD, FACP, a, and I. Bond DOa

aSan Uniformed Services Health Education Consortium (SAUSHEC), Wilford

Hall Medical Center, Lackland Air Force Base, Lackland, Texas

Available online 25 January 2008.

Objective

Tumor necrosis factor-á (TNF-á) inhibitors have emerged as a potent treatment

for rheumatoid arthritis (RA), but not without significant risks. In chronic

hepatitis B viral infection TNF-á is readily produced, and viral clearance is

dependent on the amount bioavailable. Limited data suggest that TNF-á inhibitors

may facilitate uncontrolled hepatitis B viral replication. The purpose of this

article was to provide a detailed review of the role of TNF-á in controlling

hepatitis B viral infection and the clinical impact blockade might have on viral

control.

Methods

We describe a patient with chronic hepatitis B viral infection and RA treated

with etanercept. We then review case reports, expert opinion, and manufacturer

recommendations regarding hepatitis B viral infection, TNF-á, and TNF-á

inhibitors.

Results

To date, 13 patients with chronic hepatitis B infection treated with TNF-á

inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some

patients received antiviral therapy for hepatitis B (specifically lamivudine)

before, during, or after TNF-á inhibitors were started. Clinically apparent

reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose

of infliximab. Etanercept was not associated with a similar reactivation. The

difference between infliximab and etanercept in viral reactivation may be linked

to the pharmacologic difference of each medication.

Conclusions

TNF-á inhibitors in general should be used cautiously in chronic hepatitis B

viral infection. But if necessary, when deciding which agent to use, the

clinician should consider the mechanism by which the body clears TNF-á.

Keywords: tumor necrosis factor alpha; hepatitis B; etanercept; infliximab;

adalimumab

The authors received neither financial support nor had any affiliation with

organizations outside of their respective institutions. Dr. Carroll is a

shareholder of Abbott Pharmaceuticals (adalimumab-Humira R), Amgen/Wyeth

(etanercept-Enbrel R), and Gilead Sciences (adefovir dipivoxil-Hepsera R).

Address reprint requests to B. Carroll, MD, FACP, 301 Fisher Street,

Keesler AFB, MS 39564

Note to users: The section " Articles in Press " contains peer reviewed accepted

articles to be published in this journal. When the final article is assigned to

an issue of the journal, the " Article in Press " version will be removed from

this section and will appear in the associated published journal issue. The date

it was first made available online will be carried over. Please be aware that

although " Articles in Press " do not have all bibliographic details available

yet, they can already be cited using the year of online publication and the DOI

as follows: Author(s), Article Title, Journal (Year), DOI. Please consult the

journal's reference style for the exact appearance of these elements,

abbreviation of journal names and the use of punctuation.

There are three types of " Articles in Press " :

Accepted manuscripts: these are articles that have been peer reviewed and

accepted for publication by the Editorial Board. The articles have not yet been

copy edited and/or formatted in the journal house style.

Uncorrected proofs: these are copy edited and formatted articles that are not

yet finalized and that will be corrected by the authors. Therefore the text

could change before final publication.

Corrected proofs: these are articles containing the authors' corrections and

may, or may not yet have specific issue and page numbers assigned.

Seminars in Arthritis and Rheumatism

Article in Press, Corrected Proof

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6WWX-4RNS32S-4 & _user=1\

0 & _coverDate=01%2F25%2F2008 & _rdoc=6 & _fmt=summary & _orig=browse & _srch=doc-info(%23\

toc%237142%239999%23999999999%2399999%23FLA%23display%23Articles) & _cdi=7142 & _sor\

t=d & _docanchor= & _ct=36 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=\

b2756af49fcb467bffdcb1e1efece340

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!

http://biggestloser.msn.com/

[Guest guest]

Use of Tumor Necrosis Factor-á Inhibitors in Patients with Chronic Hepatitis B

Infection

B. Carroll MD, FACP, a, and I. Bond DOa

aSan Uniformed Services Health Education Consortium (SAUSHEC), Wilford

Hall Medical Center, Lackland Air Force Base, Lackland, Texas

Available online 25 January 2008.

Objective

Tumor necrosis factor-á (TNF-á) inhibitors have emerged as a potent treatment

for rheumatoid arthritis (RA), but not without significant risks. In chronic

hepatitis B viral infection TNF-á is readily produced, and viral clearance is

dependent on the amount bioavailable. Limited data suggest that TNF-á inhibitors

may facilitate uncontrolled hepatitis B viral replication. The purpose of this

article was to provide a detailed review of the role of TNF-á in controlling

hepatitis B viral infection and the clinical impact blockade might have on viral

control.

Methods

We describe a patient with chronic hepatitis B viral infection and RA treated

with etanercept. We then review case reports, expert opinion, and manufacturer

recommendations regarding hepatitis B viral infection, TNF-á, and TNF-á

inhibitors.

Results

To date, 13 patients with chronic hepatitis B infection treated with TNF-á

inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some

patients received antiviral therapy for hepatitis B (specifically lamivudine)

before, during, or after TNF-á inhibitors were started. Clinically apparent

reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose

of infliximab. Etanercept was not associated with a similar reactivation. The

difference between infliximab and etanercept in viral reactivation may be linked

to the pharmacologic difference of each medication.

Conclusions

TNF-á inhibitors in general should be used cautiously in chronic hepatitis B

viral infection. But if necessary, when deciding which agent to use, the

clinician should consider the mechanism by which the body clears TNF-á.

Keywords: tumor necrosis factor alpha; hepatitis B; etanercept; infliximab;

adalimumab

The authors received neither financial support nor had any affiliation with

organizations outside of their respective institutions. Dr. Carroll is a

shareholder of Abbott Pharmaceuticals (adalimumab-Humira R), Amgen/Wyeth

(etanercept-Enbrel R), and Gilead Sciences (adefovir dipivoxil-Hepsera R).

Address reprint requests to B. Carroll, MD, FACP, 301 Fisher Street,

Keesler AFB, MS 39564

Note to users: The section " Articles in Press " contains peer reviewed accepted

articles to be published in this journal. When the final article is assigned to

an issue of the journal, the " Article in Press " version will be removed from

this section and will appear in the associated published journal issue. The date

it was first made available online will be carried over. Please be aware that

although " Articles in Press " do not have all bibliographic details available

yet, they can already be cited using the year of online publication and the DOI

as follows: Author(s), Article Title, Journal (Year), DOI. Please consult the

journal's reference style for the exact appearance of these elements,

abbreviation of journal names and the use of punctuation.

There are three types of " Articles in Press " :

Accepted manuscripts: these are articles that have been peer reviewed and

accepted for publication by the Editorial Board. The articles have not yet been

copy edited and/or formatted in the journal house style.

Uncorrected proofs: these are copy edited and formatted articles that are not

yet finalized and that will be corrected by the authors. Therefore the text

could change before final publication.

Corrected proofs: these are articles containing the authors' corrections and

may, or may not yet have specific issue and page numbers assigned.

Seminars in Arthritis and Rheumatism

Article in Press, Corrected Proof

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6WWX-4RNS32S-4 & _user=1\

0 & _coverDate=01%2F25%2F2008 & _rdoc=6 & _fmt=summary & _orig=browse & _srch=doc-info(%23\

toc%237142%239999%23999999999%2399999%23FLA%23display%23Articles) & _cdi=7142 & _sor\

t=d & _docanchor= & _ct=36 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=\

b2756af49fcb467bffdcb1e1efece340

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!

http://biggestloser.msn.com/

[Guest guest]

Use of Tumor Necrosis Factor-á Inhibitors in Patients with Chronic Hepatitis B

Infection

B. Carroll MD, FACP, a, and I. Bond DOa

aSan Uniformed Services Health Education Consortium (SAUSHEC), Wilford

Hall Medical Center, Lackland Air Force Base, Lackland, Texas

Available online 25 January 2008.

Objective

Tumor necrosis factor-á (TNF-á) inhibitors have emerged as a potent treatment

for rheumatoid arthritis (RA), but not without significant risks. In chronic

hepatitis B viral infection TNF-á is readily produced, and viral clearance is

dependent on the amount bioavailable. Limited data suggest that TNF-á inhibitors

may facilitate uncontrolled hepatitis B viral replication. The purpose of this

article was to provide a detailed review of the role of TNF-á in controlling

hepatitis B viral infection and the clinical impact blockade might have on viral

control.

Methods

We describe a patient with chronic hepatitis B viral infection and RA treated

with etanercept. We then review case reports, expert opinion, and manufacturer

recommendations regarding hepatitis B viral infection, TNF-á, and TNF-á

inhibitors.

Results

To date, 13 patients with chronic hepatitis B infection treated with TNF-á

inhibitors have been reported: 11 with infliximab and 2 with etanercept. Some

patients received antiviral therapy for hepatitis B (specifically lamivudine)

before, during, or after TNF-á inhibitors were started. Clinically apparent

reactivation of hepatitis B virus typically occurred 1 month after the 3rd dose

of infliximab. Etanercept was not associated with a similar reactivation. The

difference between infliximab and etanercept in viral reactivation may be linked

to the pharmacologic difference of each medication.

Conclusions

TNF-á inhibitors in general should be used cautiously in chronic hepatitis B

viral infection. But if necessary, when deciding which agent to use, the

clinician should consider the mechanism by which the body clears TNF-á.

Keywords: tumor necrosis factor alpha; hepatitis B; etanercept; infliximab;

adalimumab

The authors received neither financial support nor had any affiliation with

organizations outside of their respective institutions. Dr. Carroll is a

shareholder of Abbott Pharmaceuticals (adalimumab-Humira R), Amgen/Wyeth

(etanercept-Enbrel R), and Gilead Sciences (adefovir dipivoxil-Hepsera R).

Address reprint requests to B. Carroll, MD, FACP, 301 Fisher Street,

Keesler AFB, MS 39564

Note to users: The section " Articles in Press " contains peer reviewed accepted

articles to be published in this journal. When the final article is assigned to

an issue of the journal, the " Article in Press " version will be removed from

this section and will appear in the associated published journal issue. The date

it was first made available online will be carried over. Please be aware that

although " Articles in Press " do not have all bibliographic details available

yet, they can already be cited using the year of online publication and the DOI

as follows: Author(s), Article Title, Journal (Year), DOI. Please consult the

journal's reference style for the exact appearance of these elements,

abbreviation of journal names and the use of punctuation.

There are three types of " Articles in Press " :

Accepted manuscripts: these are articles that have been peer reviewed and

accepted for publication by the Editorial Board. The articles have not yet been

copy edited and/or formatted in the journal house style.

Uncorrected proofs: these are copy edited and formatted articles that are not

yet finalized and that will be corrected by the authors. Therefore the text

could change before final publication.

Corrected proofs: these are articles containing the authors' corrections and

may, or may not yet have specific issue and page numbers assigned.

Seminars in Arthritis and Rheumatism

Article in Press, Corrected Proof

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6WWX-4RNS32S-4 & _user=1\

0 & _coverDate=01%2F25%2F2008 & _rdoc=6 & _fmt=summary & _orig=browse & _srch=doc-info(%23\

toc%237142%239999%23999999999%2399999%23FLA%23display%23Articles) & _cdi=7142 & _sor\

t=d & _docanchor= & _ct=36 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md5=\

b2756af49fcb467bffdcb1e1efece340

_________________________________________________________________

Shed those extra pounds with MSN and The Biggest Loser!

http://biggestloser.msn.com/