Hepatitis B Virus Mutations and Chronic Hepatitis B Clinical Outcomes During Pregnancy and Post-Partum Follow-up
Bibliographic record
Abstract
Chronic hepatitis B (CHB) is a dynamic disease, that may be affected by host immunological changes in pregnancy. Certain HBV genotypes (i.e., C vs B) and HBV core (C), basal core promoter (BCP) and surface (S) variants are associated with increased liver disease risk, and rarely linked to vaccine failure due to mother-to-child transmission (MTCT) of vaccine escape mutants (VEM). In highly viremic mothers guidelines recommend consideration of nucleos/tide analogs (NA) therapy targeting the HBV polymerase (P) to reduce MTCT risk. AIM : To follow untreated and NA-treated CHB carriers during pregnancy until ~ 6 months postpartum to assess HBV viral load, liver enzymes and HBV eAg (HBeAg) status, and to evaluate for changes in the HBV genome. METHODS: In this prospective study, demographic and clinical data were collected from 21 women recruited in the 2 nd trimester (one with 2 pregnancies), and during post-partum follow-up. In plasma collected during pregnancy (20/21), and post-partum (11/21), the HBV pre-S/S overlapping P region in all, and the HBV pre-C/C gene (9/21 to date) were PCR amplified, amplicons cloned and ~15 clones/plasma sample sequenced and analyzed with MEGA V5.0. Maternal clinical outcomes assessed included changes in HBV DNA, quantitative HBV surface antigen (qHBsAg) titres, ALT and HBeAg serconversion. RESULTS: In 21 patients (median age 31 y, 62% Asian with genotype B or C, 41% HBeAg+, 23% (5/21) were treated with TDF to reduce maternal viremia (median baseline HBV DNA 8.5 log IU/ml). In 16 untreated patients, the median baseline vs postpartum ALT increased (19.5 [range 6-43] vs 24.5 [range 7- 64], P<0.01) albeit with no significant change in HBV DNA (2.7 vs 2.4 log10 IU/ml). All had normal post-partum liver stiffness measurement (LSM) by transient elastography (median LSM 4.7 kpa, range 2.8-6.1) and none had HBeAg loss. Clonal sequencing analysis of the HBV preS/S/overlapping P region showed that patients often carried minor variants associated with immune escape (N=12) and liver disease (N=8), as well as NA resistance (N=4). Clonal sequencing analysis of the HBV pre C/C region in 9 patients to date showed that patients often carried pre C variants (N=7), only a few had carried BCP variants (N=1). SUMMARY : CHB carriers followed during pregnancy and post-partum often experience mild ALT elevations from baseline and carry minor HBV variants at residues associated with vaccine escape, liver disease and NA resistance. Analysis of the pre C/C region to date showed variants associated with HBeAg(-) CHB and increased risk of liver disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".