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 machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".