The Incidence and Clinical Outcome of YMDD Mutants in Hepatitis B Surface Antigen-Positive Renal All

[Guest guest]

Kidney transplantation

The Incidence and Clinical Outcome of YMDD Mutants in Hepatitis B Surface

Antigen-Positive Renal Allograft Recipients After Prolonged Lamivudine Therapy

G.-Y. Gwaka, W. Huha, , , D.H. Leea, M.S. Choia, J.H. Leea, K.C. Koha, S.-J.

Kimb, J.-W. Johb and H.-Y. Oha

aDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea

bDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea.

Available online 21 December 2007.

Abstract

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV),

prolonged therapy may induce the development of LAM-resistant strains, YMDD

mutants. Although YMDD mutants have impaired replication that leads to a benign

clinical course compared with wild-type virus, some immunosuppressive agents may

enhance replication of YMDD mutants, causing a severe hepatitis flare. We

retrospectively investigated the incidence and clinical outcomes of YMDD mutants

in renal allograft recipients on immunosuppressive treatment. Clinical records

of 25 renal allograft recipients, who underwent renal transplantation between

December 1997 and February 2006 were hepatitis B surface antigen positive at the

time of transplantation, were reviewed. All patients received LAM treatment

after renal transplantation. Over 9 to 98 months of follow-up, 16 patients

(64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%)

showed persistent or increased levels of HBV DNA. Seven were identified as

having developed YMDD mutants. Although genotypic analysis was not performed,

YMDD mutants were strongly suspected in another two patients, who developed

severe hepatic dysfunction combined with high levels of HBV viremia at close to

2 years of LAM therapy. One patient recovered after hepatic transplantation and

another patient died of hepatic failure. In conclusion, the incidence of YMDD

mutants was similar to that of nonimmunosuppressed individuals; however, the

presence of these mutants made it more likely for severe liver disease to

develop in renal transplant recipients. Therefore, close monitoring for the

development of YMDD mutants should be performed during LAM treatment, especially

in this group of patients.

Address reprint requests to Wooseong Huh, MD, Department of Medicine, Samsung

Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong,

Gangnam-Gu, 135-710, Seoul, Republic of Korea.

Transplantation Proceedings

Volume 39, Issue 10, December 2007, Pages 3121-3126

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6VJ0-4RD9KMT-1D & _user=\

10 & _coverDate=12%2F31%2F2007 & _rdoc=40 & _fmt=summary & _orig=browse & _srch=doc-info(%\

23toc%236080%232007%23999609989%23677001%23FLA%23display%23Volume) & _cdi=6080 & _so\

rt=d & _docanchor= & _ct=139 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md\

5=5b7959cc1c308f59d22d5f1606bf19f0

_________________________________________________________________

Watch “Cause Effect,” a show about real people making a real difference.

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[Guest guest]

Kidney transplantation

The Incidence and Clinical Outcome of YMDD Mutants in Hepatitis B Surface

Antigen-Positive Renal Allograft Recipients After Prolonged Lamivudine Therapy

G.-Y. Gwaka, W. Huha, , , D.H. Leea, M.S. Choia, J.H. Leea, K.C. Koha, S.-J.

Kimb, J.-W. Johb and H.-Y. Oha

aDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea

bDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea.

Available online 21 December 2007.

Abstract

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV),

prolonged therapy may induce the development of LAM-resistant strains, YMDD

mutants. Although YMDD mutants have impaired replication that leads to a benign

clinical course compared with wild-type virus, some immunosuppressive agents may

enhance replication of YMDD mutants, causing a severe hepatitis flare. We

retrospectively investigated the incidence and clinical outcomes of YMDD mutants

in renal allograft recipients on immunosuppressive treatment. Clinical records

of 25 renal allograft recipients, who underwent renal transplantation between

December 1997 and February 2006 were hepatitis B surface antigen positive at the

time of transplantation, were reviewed. All patients received LAM treatment

after renal transplantation. Over 9 to 98 months of follow-up, 16 patients

(64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%)

showed persistent or increased levels of HBV DNA. Seven were identified as

having developed YMDD mutants. Although genotypic analysis was not performed,

YMDD mutants were strongly suspected in another two patients, who developed

severe hepatic dysfunction combined with high levels of HBV viremia at close to

2 years of LAM therapy. One patient recovered after hepatic transplantation and

another patient died of hepatic failure. In conclusion, the incidence of YMDD

mutants was similar to that of nonimmunosuppressed individuals; however, the

presence of these mutants made it more likely for severe liver disease to

develop in renal transplant recipients. Therefore, close monitoring for the

development of YMDD mutants should be performed during LAM treatment, especially

in this group of patients.

Address reprint requests to Wooseong Huh, MD, Department of Medicine, Samsung

Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong,

Gangnam-Gu, 135-710, Seoul, Republic of Korea.

Transplantation Proceedings

Volume 39, Issue 10, December 2007, Pages 3121-3126

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6VJ0-4RD9KMT-1D & _user=\

10 & _coverDate=12%2F31%2F2007 & _rdoc=40 & _fmt=summary & _orig=browse & _srch=doc-info(%\

23toc%236080%232007%23999609989%23677001%23FLA%23display%23Volume) & _cdi=6080 & _so\

rt=d & _docanchor= & _ct=139 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md\

5=5b7959cc1c308f59d22d5f1606bf19f0

_________________________________________________________________

Watch “Cause Effect,” a show about real people making a real difference.

http://im.live.com/Messenger/IM/MTV/?source=text_watchcause

[Guest guest]

Kidney transplantation

The Incidence and Clinical Outcome of YMDD Mutants in Hepatitis B Surface

Antigen-Positive Renal Allograft Recipients After Prolonged Lamivudine Therapy

G.-Y. Gwaka, W. Huha, , , D.H. Leea, M.S. Choia, J.H. Leea, K.C. Koha, S.-J.

Kimb, J.-W. Johb and H.-Y. Oha

aDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea

bDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea.

Available online 21 December 2007.

Abstract

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV),

prolonged therapy may induce the development of LAM-resistant strains, YMDD

mutants. Although YMDD mutants have impaired replication that leads to a benign

clinical course compared with wild-type virus, some immunosuppressive agents may

enhance replication of YMDD mutants, causing a severe hepatitis flare. We

retrospectively investigated the incidence and clinical outcomes of YMDD mutants

in renal allograft recipients on immunosuppressive treatment. Clinical records

of 25 renal allograft recipients, who underwent renal transplantation between

December 1997 and February 2006 were hepatitis B surface antigen positive at the

time of transplantation, were reviewed. All patients received LAM treatment

after renal transplantation. Over 9 to 98 months of follow-up, 16 patients

(64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%)

showed persistent or increased levels of HBV DNA. Seven were identified as

having developed YMDD mutants. Although genotypic analysis was not performed,

YMDD mutants were strongly suspected in another two patients, who developed

severe hepatic dysfunction combined with high levels of HBV viremia at close to

2 years of LAM therapy. One patient recovered after hepatic transplantation and

another patient died of hepatic failure. In conclusion, the incidence of YMDD

mutants was similar to that of nonimmunosuppressed individuals; however, the

presence of these mutants made it more likely for severe liver disease to

develop in renal transplant recipients. Therefore, close monitoring for the

development of YMDD mutants should be performed during LAM treatment, especially

in this group of patients.

Address reprint requests to Wooseong Huh, MD, Department of Medicine, Samsung

Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong,

Gangnam-Gu, 135-710, Seoul, Republic of Korea.

Transplantation Proceedings

Volume 39, Issue 10, December 2007, Pages 3121-3126

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6VJ0-4RD9KMT-1D & _user=\

10 & _coverDate=12%2F31%2F2007 & _rdoc=40 & _fmt=summary & _orig=browse & _srch=doc-info(%\

23toc%236080%232007%23999609989%23677001%23FLA%23display%23Volume) & _cdi=6080 & _so\

rt=d & _docanchor= & _ct=139 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md\

5=5b7959cc1c308f59d22d5f1606bf19f0

_________________________________________________________________

Watch “Cause Effect,” a show about real people making a real difference.

http://im.live.com/Messenger/IM/MTV/?source=text_watchcause

[Guest guest]

Kidney transplantation

The Incidence and Clinical Outcome of YMDD Mutants in Hepatitis B Surface

Antigen-Positive Renal Allograft Recipients After Prolonged Lamivudine Therapy

G.-Y. Gwaka, W. Huha, , , D.H. Leea, M.S. Choia, J.H. Leea, K.C. Koha, S.-J.

Kimb, J.-W. Johb and H.-Y. Oha

aDepartment of Medicine, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea

bDepartment of Surgery, Samsung Medical Center, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea.

Available online 21 December 2007.

Abstract

Although lamivudine (LAM) is a potent inhibitor of hepatitis B virus (HBV),

prolonged therapy may induce the development of LAM-resistant strains, YMDD

mutants. Although YMDD mutants have impaired replication that leads to a benign

clinical course compared with wild-type virus, some immunosuppressive agents may

enhance replication of YMDD mutants, causing a severe hepatitis flare. We

retrospectively investigated the incidence and clinical outcomes of YMDD mutants

in renal allograft recipients on immunosuppressive treatment. Clinical records

of 25 renal allograft recipients, who underwent renal transplantation between

December 1997 and February 2006 were hepatitis B surface antigen positive at the

time of transplantation, were reviewed. All patients received LAM treatment

after renal transplantation. Over 9 to 98 months of follow-up, 16 patients

(64.0%) maintained undetectable HBV DNA levels; however, 9 patients (36.0%)

showed persistent or increased levels of HBV DNA. Seven were identified as

having developed YMDD mutants. Although genotypic analysis was not performed,

YMDD mutants were strongly suspected in another two patients, who developed

severe hepatic dysfunction combined with high levels of HBV viremia at close to

2 years of LAM therapy. One patient recovered after hepatic transplantation and

another patient died of hepatic failure. In conclusion, the incidence of YMDD

mutants was similar to that of nonimmunosuppressed individuals; however, the

presence of these mutants made it more likely for severe liver disease to

develop in renal transplant recipients. Therefore, close monitoring for the

development of YMDD mutants should be performed during LAM treatment, especially

in this group of patients.

Address reprint requests to Wooseong Huh, MD, Department of Medicine, Samsung

Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong,

Gangnam-Gu, 135-710, Seoul, Republic of Korea.

Transplantation Proceedings

Volume 39, Issue 10, December 2007, Pages 3121-3126

http://www.sciencedirect.com/science?_ob=ArticleURL & _udi=B6VJ0-4RD9KMT-1D & _user=\

10 & _coverDate=12%2F31%2F2007 & _rdoc=40 & _fmt=summary & _orig=browse & _srch=doc-info(%\

23toc%236080%232007%23999609989%23677001%23FLA%23display%23Volume) & _cdi=6080 & _so\

rt=d & _docanchor= & _ct=139 & _acct=C000050221 & _version=1 & _urlVersion=0 & _userid=10 & md\

5=5b7959cc1c308f59d22d5f1606bf19f0

_________________________________________________________________

Watch “Cause Effect,” a show about real people making a real difference.

http://im.live.com/Messenger/IM/MTV/?source=text_watchcause