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Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up.

Virine B, Osiowy C, Gao S, Wang T, Castillo E, Martin SR, Lee SS, Simmonds K, van Marle G, Coffin CS - PLoS ONE (2015)

Bottom Line: Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy.The presence of minor VEM warrant infant follow-up.

View Article: PubMed Central - PubMed

Affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB, Canada.

ABSTRACT

Background: Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection.

Objectives: To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers.

Study design: In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis.

Results: The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor "a determinant" and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.

Conclusions: Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.

No MeSH data available.


Related in: MedlinePlus

Neighbor-joining phylogenetic reconstruction of the HBV pre-S/S (A, N = 20), Pre-C/C (B, N = 11) and full genome (C, N = 3) using the bootstrap method.Clustering is prominent between individual cases, indicating a greater degree of variation between individuals, than amongst each of their viral quasispecies. Bootstrap values greater than 70 were considered significant. Case #146 was excluded from analysis as only the pre-S1 region was sequenced.
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pone.0140070.g001: Neighbor-joining phylogenetic reconstruction of the HBV pre-S/S (A, N = 20), Pre-C/C (B, N = 11) and full genome (C, N = 3) using the bootstrap method.Clustering is prominent between individual cases, indicating a greater degree of variation between individuals, than amongst each of their viral quasispecies. Bootstrap values greater than 70 were considered significant. Case #146 was excluded from analysis as only the pre-S1 region was sequenced.

Mentions: a Both pregnant and post-partum samples were analyzed from Cases 128, 160, 176, 196, 215, 223, 226 and 233 in the pre S/S and/or in the pre-C/C region (see Fig 1A and 1B). Case #176 was followed during 2 pregnancies, HBV pre-S/S/P sequences were analyzed in a sample collected after her first pregnancy (176–2 post-partum) and during her second pregnancy (176–3). HBV Pre-C/C sequences were analyzed at 3 time-points during first pregnancy (176), post-partum (176–2) and during second pregnancy (176–3) (see Figs 1 and 2).


Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up.

Virine B, Osiowy C, Gao S, Wang T, Castillo E, Martin SR, Lee SS, Simmonds K, van Marle G, Coffin CS - PLoS ONE (2015)

Neighbor-joining phylogenetic reconstruction of the HBV pre-S/S (A, N = 20), Pre-C/C (B, N = 11) and full genome (C, N = 3) using the bootstrap method.Clustering is prominent between individual cases, indicating a greater degree of variation between individuals, than amongst each of their viral quasispecies. Bootstrap values greater than 70 were considered significant. Case #146 was excluded from analysis as only the pre-S1 region was sequenced.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608582&req=5

pone.0140070.g001: Neighbor-joining phylogenetic reconstruction of the HBV pre-S/S (A, N = 20), Pre-C/C (B, N = 11) and full genome (C, N = 3) using the bootstrap method.Clustering is prominent between individual cases, indicating a greater degree of variation between individuals, than amongst each of their viral quasispecies. Bootstrap values greater than 70 were considered significant. Case #146 was excluded from analysis as only the pre-S1 region was sequenced.
Mentions: a Both pregnant and post-partum samples were analyzed from Cases 128, 160, 176, 196, 215, 223, 226 and 233 in the pre S/S and/or in the pre-C/C region (see Fig 1A and 1B). Case #176 was followed during 2 pregnancies, HBV pre-S/S/P sequences were analyzed in a sample collected after her first pregnancy (176–2 post-partum) and during her second pregnancy (176–3). HBV Pre-C/C sequences were analyzed at 3 time-points during first pregnancy (176), post-partum (176–2) and during second pregnancy (176–3) (see Figs 1 and 2).

Bottom Line: Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy.The presence of minor VEM warrant infant follow-up.

View Article: PubMed Central - PubMed

Affiliation: Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, 3280 Hospital Drive NW, University of Calgary, Calgary, AB, Canada.

ABSTRACT

Background: Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection.

Objectives: To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers.

Study design: In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis.

Results: The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor "a determinant" and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity.

Conclusions: Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.

No MeSH data available.


Related in: MedlinePlus