Vol.:(0123456789) 1 3 Digestive Diseases and Sciences https://doi.org/10.1007/s10620-019-05745-w ORIGINAL ARTICLE Presence of Precore (C)/C Promoter Mutants in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B (CHB) Carriers During Pregnancy Does Not Correlate with Increased Risk of Liver Disease in 4 Years of Follow‑Up Shivali S. Joshi 1,2  · Shan Gao 1,2  · Eliana Castillo 3  · Carla S. Coffin 1,2 Received: 3 April 2019 / Accepted: 18 July 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose HBV precore (PC) and basal core promoter (BCP) mutants are associated with liver disease severity, yet have been suggested to protect against HBV vertical transmission. HBV within peripheral blood mononuclear cells (PBMC) has been reported in association with intrauterine HBV infection. We analyzed HBV replication status in PBMC and PC/BCP mutants in PBMC from pregnant chronic hepatitis B (CHB) patients. Methods Pregnant CHB carriers were assessed for HBeAg, HBV-DNA, ALT in second–third trimester and liver stiffness measurement (LSM) postpartum. HBV-DNA, HBV-cccDNA, and HBV-mRNA were tested in PBMC by in-house PCR. BCP/PC variants were determined by Sanger sequencing and analyzed using MEGA7. Results In 37 CHB pregnant carriers, median age 32 years, 53% Asian, median ALT 19 versus 26 U/L, median HBV-DNA 2.6 versus 8.1 logIU/mL (untreated vs. treated), eight HBeAg + , with genotype 10%A, 29%B, 21%C, 10%D, 19%E, eight received tenofovir in pregnancy to reduce vertical transmission risk. HBV-DNA was detected in ~ 55% (25/45) PBMC, and PC/BCP mutations were found in 36% (9/25) and 4% (1/25), respectively. All infants received HBV immunoprophylaxis and tested HBV surface antigen negative at 9–12 months of age. During a median 4 years (IQR 3–5), follow-up all moth- ers showed normal LSM, with no significant change in ALT, HBeAg status, or HBV-DNA levels compared to baseline in untreated CHB carriers. Conclusion In this multiethnic cohort of pregnant CHB carriers, HBV replicative intermediates and PC/BCP mutants were found in significant proportion of PBMC, but were not associated with increased risk of HBV immunoprophylaxis failure or liver disease severity over long-term follow-up. Keywords Chronic hepatitis B · Pregnancy · HBV genomes · HBV variants · PBMC · Long-term follow-up Abbreviations HBV Hepatitis B virus HCC Hepatocellular carcinoma MTCT Mother-to-child transmission CHB Chronic hepatitis B HBIG Hepatitis B immune globulin PBMC Peripheral blood mononuclear cells PC Precore BCP Basal core promoter HBeAg Hepatitis B e antigen ALT Alanine transaminase Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10620-019-05745-w) contains supplementary material, which is available to authorized users. * Carla S. Coffin cscoffin@ucalgary.ca 1 Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W., Calgary, AB T2N 4Z6, Canada 2 Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Canada 3 Section of Maternal Fetal Medicine, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Canada