Hepatitis B virus (HBV) quasispecies in hepatic and extrahepatic viral reservoirs in liver transplant recipients on prophylactic therapy

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/lt.22312/abstract

Original Articles

Hepatitis B virus (HBV) quasispecies in hepatic and extrahepatic viral

reservoirs in liver transplant recipients on prophylactic therapy

Carla S. Coffin1,*,†, M. Mulrooney-Cousins2, Guido van Marle3, P.

4, Tomasz I. Michalak2, Norah A. Terrault5DOI:

10.1002/lt.22312

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Liver Transplantation

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Characterization of hepatitis B virus (HBV) quasispecies in different

compartments in liver transplant (LT) recipients may help optimize prophylaxis

regimens.

Aims:

To evaluate liver, peripheral blood mononuclear cells (PBMC) and plasma for HBV

and compare quasispecies in hepatic vs. extrahepatic sites in LT recipients on

long-term prophylaxis.

Methods:

Liver, plasma and PBMC from 12 patients followed for up to 15 years post-LT (all

HBV DNA negative by conventional PCR assays) were evaluated for HBV DNA by

sensitive nested PCR, covalently closed circular DNA (cccDNA) in liver/PBMC, and

sequencing, and phylogenetic analysis of polymerase (P) quasispecies.

Results:

In 10 patients with no clinical recurrence on prophylaxis (median post-LT 15.5

mo, range 12-96), 9/10 of liver, 3/10 of plasma, and 2/7 of PBMC were HBV

DNA-reactive, including one with HBV cccDNA in PBMC. Sequence analysis showed

all HBV clones with wild-type sequence in liver and PBMC. In 2 patients with

early HBV recurrence post-LT, treated with nucleosides only, HBV DNA was

detected in serum, PBMC and liver and HBV cccDNA was found in liver. HBV M204I

lamivudine resistant (LMVr) variant was identified in liver (66% and 70% clones)

and in plasma (100% clones), but wild-type sequence in 100% of PBMC clones.

Conclusions:

Despite prophylaxis and absence of HBV DNA by conventional assays, HBV is

detectable in serum, liver and PBMC in almost all patients, supporting the use

of continued anti-HBV therapy in this group. Antiviral drug resistant variants

are more frequent in liver than in PBMC but both compartments are potential

sources for reinfection. Liver Transpl, 2011. © 2011 AASLD.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/lt.22312/abstract

Original Articles

Hepatitis B virus (HBV) quasispecies in hepatic and extrahepatic viral

reservoirs in liver transplant recipients on prophylactic therapy

Carla S. Coffin1,*,†, M. Mulrooney-Cousins2, Guido van Marle3, P.

4, Tomasz I. Michalak2, Norah A. Terrault5DOI:

10.1002/lt.22312

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Liver Transplantation

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Characterization of hepatitis B virus (HBV) quasispecies in different

compartments in liver transplant (LT) recipients may help optimize prophylaxis

regimens.

Aims:

To evaluate liver, peripheral blood mononuclear cells (PBMC) and plasma for HBV

and compare quasispecies in hepatic vs. extrahepatic sites in LT recipients on

long-term prophylaxis.

Methods:

Liver, plasma and PBMC from 12 patients followed for up to 15 years post-LT (all

HBV DNA negative by conventional PCR assays) were evaluated for HBV DNA by

sensitive nested PCR, covalently closed circular DNA (cccDNA) in liver/PBMC, and

sequencing, and phylogenetic analysis of polymerase (P) quasispecies.

Results:

In 10 patients with no clinical recurrence on prophylaxis (median post-LT 15.5

mo, range 12-96), 9/10 of liver, 3/10 of plasma, and 2/7 of PBMC were HBV

DNA-reactive, including one with HBV cccDNA in PBMC. Sequence analysis showed

all HBV clones with wild-type sequence in liver and PBMC. In 2 patients with

early HBV recurrence post-LT, treated with nucleosides only, HBV DNA was

detected in serum, PBMC and liver and HBV cccDNA was found in liver. HBV M204I

lamivudine resistant (LMVr) variant was identified in liver (66% and 70% clones)

and in plasma (100% clones), but wild-type sequence in 100% of PBMC clones.

Conclusions:

Despite prophylaxis and absence of HBV DNA by conventional assays, HBV is

detectable in serum, liver and PBMC in almost all patients, supporting the use

of continued anti-HBV therapy in this group. Antiviral drug resistant variants

are more frequent in liver than in PBMC but both compartments are potential

sources for reinfection. Liver Transpl, 2011. © 2011 AASLD.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/lt.22312/abstract

Original Articles

Hepatitis B virus (HBV) quasispecies in hepatic and extrahepatic viral

reservoirs in liver transplant recipients on prophylactic therapy

Carla S. Coffin1,*,†, M. Mulrooney-Cousins2, Guido van Marle3, P.

4, Tomasz I. Michalak2, Norah A. Terrault5DOI:

10.1002/lt.22312

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Liver Transplantation

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Characterization of hepatitis B virus (HBV) quasispecies in different

compartments in liver transplant (LT) recipients may help optimize prophylaxis

regimens.

Aims:

To evaluate liver, peripheral blood mononuclear cells (PBMC) and plasma for HBV

and compare quasispecies in hepatic vs. extrahepatic sites in LT recipients on

long-term prophylaxis.

Methods:

Liver, plasma and PBMC from 12 patients followed for up to 15 years post-LT (all

HBV DNA negative by conventional PCR assays) were evaluated for HBV DNA by

sensitive nested PCR, covalently closed circular DNA (cccDNA) in liver/PBMC, and

sequencing, and phylogenetic analysis of polymerase (P) quasispecies.

Results:

In 10 patients with no clinical recurrence on prophylaxis (median post-LT 15.5

mo, range 12-96), 9/10 of liver, 3/10 of plasma, and 2/7 of PBMC were HBV

DNA-reactive, including one with HBV cccDNA in PBMC. Sequence analysis showed

all HBV clones with wild-type sequence in liver and PBMC. In 2 patients with

early HBV recurrence post-LT, treated with nucleosides only, HBV DNA was

detected in serum, PBMC and liver and HBV cccDNA was found in liver. HBV M204I

lamivudine resistant (LMVr) variant was identified in liver (66% and 70% clones)

and in plasma (100% clones), but wild-type sequence in 100% of PBMC clones.

Conclusions:

Despite prophylaxis and absence of HBV DNA by conventional assays, HBV is

detectable in serum, liver and PBMC in almost all patients, supporting the use

of continued anti-HBV therapy in this group. Antiviral drug resistant variants

are more frequent in liver than in PBMC but both compartments are potential

sources for reinfection. Liver Transpl, 2011. © 2011 AASLD.

[Guest guest]

http://onlinelibrary.wiley.com/doi/10.1002/lt.22312/abstract

Original Articles

Hepatitis B virus (HBV) quasispecies in hepatic and extrahepatic viral

reservoirs in liver transplant recipients on prophylactic therapy

Carla S. Coffin1,*,†, M. Mulrooney-Cousins2, Guido van Marle3, P.

4, Tomasz I. Michalak2, Norah A. Terrault5DOI:

10.1002/lt.22312

Copyright © 2011 American Association for the Study of Liver Diseases

Issue

Liver Transplantation

Accepted Article (Accepted, unedited articles published online for future

issues)

Abstract

Characterization of hepatitis B virus (HBV) quasispecies in different

compartments in liver transplant (LT) recipients may help optimize prophylaxis

regimens.

Aims:

To evaluate liver, peripheral blood mononuclear cells (PBMC) and plasma for HBV

and compare quasispecies in hepatic vs. extrahepatic sites in LT recipients on

long-term prophylaxis.

Methods:

Liver, plasma and PBMC from 12 patients followed for up to 15 years post-LT (all

HBV DNA negative by conventional PCR assays) were evaluated for HBV DNA by

sensitive nested PCR, covalently closed circular DNA (cccDNA) in liver/PBMC, and

sequencing, and phylogenetic analysis of polymerase (P) quasispecies.

Results:

In 10 patients with no clinical recurrence on prophylaxis (median post-LT 15.5

mo, range 12-96), 9/10 of liver, 3/10 of plasma, and 2/7 of PBMC were HBV

DNA-reactive, including one with HBV cccDNA in PBMC. Sequence analysis showed

all HBV clones with wild-type sequence in liver and PBMC. In 2 patients with

early HBV recurrence post-LT, treated with nucleosides only, HBV DNA was

detected in serum, PBMC and liver and HBV cccDNA was found in liver. HBV M204I

lamivudine resistant (LMVr) variant was identified in liver (66% and 70% clones)

and in plasma (100% clones), but wild-type sequence in 100% of PBMC clones.

Conclusions:

Despite prophylaxis and absence of HBV DNA by conventional assays, HBV is

detectable in serum, liver and PBMC in almost all patients, supporting the use

of continued anti-HBV therapy in this group. Antiviral drug resistant variants

are more frequent in liver than in PBMC but both compartments are potential

sources for reinfection. Liver Transpl, 2011. © 2011 AASLD.