The Changing Global Epidemiology of Hepatocellular Carcinoma.

Hepatocellular carcinoma is among the leading causes of morbidity and mortality. Owing to the current epidemic of metabolic syndrome, the population affected by nonalcoholic fatty liver disease/nonalcoholic steatohepatitis continues to increase and now comprises a significant portion with those with hepatocellular carcinoma. The World Health Organization goal of obtaining universal hepatitis B virus vaccination has led to a global effort to improve vaccination, prevent mother-to-child transmission, and implement linkage to care to avoid the development of hepatocellular carcinoma. In contrast with the decreased burden of chronic hepatitis C virus, there has been an increase in new-onset acute hepatitis C virus.

Hepatitis B Virus Infection in Pregnancy: An Update on Evidence-Based Management.

IMPORTANCE: Vertical hepatitis B virus (HBV) transmission is the important route of chronic HBV infection. Although infant immunoprophylaxis is effective, a significant number of infants still become infected, most are associated with intrauterine infection. New evidences support intrauterine treatment in cases of high risk. OBJECTIVE: The aim of this study was to review the current evidences and recommendations for management of HBV infection in pregnancy. EVIDENCE ACQUISITION: Original research articles, review articles, and guidelines were reviewed. RESULTS: The management can be summarized as follows: (1) all pregnant women should be screened for hepatitis B surface antigen (HBsAg) and antibody to HBsAg. High-risk HBsAg-negative pregnant women without immunity should be vaccinated during pregnancy. (2) HBsAg-positive pregnant women should undergo further workup for liver status and indicative factors for immunoprophylaxis failure. (3) Pregnant women should be treated with HBV DNA levels greater than 200,000 IU/mL or 6 log copies/mL. (4) Antiviral drug should be started around 28 to 32 weeks. The first-line drug is tenofovir disoproxil fumarate. (5) Delivery route should be chosen based only on obstetric indications. (6) Breastfeeding is not contraindicated because it does not increase the risk of transmission in neonates with HBV vaccine and immunoglobulin administration. (7) Neonates born to HBsAg-positive mothers should receive HBV vaccine and immunoglobulin after birth as soon as possible. (8) Follow-up of the mothers and neonates is important. Beware of hepatitis flare after birth and after antiretroviral drug discontinuation; alanine transaminase assessment every 1 to 3 months until 6 months is suggested. Also, the schedule of infant vaccination and follow-up of serologic testing at 9 to 12 months old is needed.

Efficacy and Safety of Tenofovir in the Prevention of Perinatal Transmission of Hepatitis B, a Meta-Analysis.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is recommended for the prevention of perinatal transmission of the hepatitis B virus (HBV). This study aimed to systematically assess the efficacy and safety of TDF in pregnant women with chronic HBV and their infants. MATERIAL AND METHODS: Database searches were performed to identify studies blocking the mother-to-child transmission of the hepatitis B virus with tenofovir. The search included pregnant women with chronic HBV infection administered with TDF compared to the no treatment controls, and data from individual studies were pooled using RevMan v5.3 for meta-analysis. RESULTS: Seven studies with a total of 911 patients met the inclusion criteria: 433 patients in the TDF group and 478 patients in the non-TDF group. The HBV mother-to-child transmission rate in the tenofovir group was effectively reduced compared to the control group (RR: 0.18, 95% CI: 0.08-0.40). HBV-DNA positivity was also significantly low in infants from TDF group (RR: 0.17, 95% CI: 0.10-0.30) and the TDF treatment resulted in significantly higher anti-HBs production (RR: 1.11, 95% CI: 1.04-1.18). Similarly, maternal HBV-DNA was suppression was significantly high in the TDF group (RR: 34.16, 95% CI: 16.40-71.13). Women treated with TDF and their infants did not result in serious adverse events that are statistically different as compared to the women who did not receive any treatment. CONCLUSION: Treatment of HBV infected pregnant women with TDF can effectively and safely prevent the perinatal transmission of chronic hepatitis B.

Trends in Hepatitis B Surveillance Among Pregnant Women in New York City, 1998-2015.

OBJECTIVE: Infants born to women with hepatitis B virus (HBV) infection are at high risk for chronic HBV infection and premature death. We examined epidemiologic trends among women with HBV infection who gave birth in New York City (NYC) to inform public health prevention activities. METHODS: We obtained data on HBV-infected women residing and giving birth in NYC during 1998-2015 from the NYC Perinatal HBV Prevention Program. We obtained citywide birth data from the NYC Office of Vital Statistics. We calculated the incidence of births to HBV-infected women per 100 000 live births and stratified by maternal race, birthplace, and age. We calculated annual percentage change (APC) in incidence of births to HBV-infected women by using joinpoint regression. RESULTS: Of 29 896 HBV-infected women included in the study, 28 195 (94.3%) were non-US-born, of whom 16 600 (58.9%) were born in China. Overall incidence of births to HBV-infected women per 100 000 live births increased from 1156 in 1998 to 1573 in 2006 (APC = 3.1%; P < .001) but declined to 1329 in 2015 (APC = -1.4%; P = .02). Incidence among US-born women declined from 1998 to 2015 (330 to 84; APC = -7.3%; P < .001) and among non-US-born women increased from 1998 to 2007 (1877 to 2864; APC = 3.6%; P < .001) but not thereafter. Incidence among women born in China increased from 1998 to 2006 (13 275 to 16 480; APC = 1.8%; P = .02) but decreased to 12 631 through 2015 (APC = -3.3%; P < .001). CONCLUSIONS: The incidence of births to HBV-infected women in NYC declined significantly among US-born women but not among non-US-born women, highlighting the need for successful vaccination programs worldwide.

Efficacy and safety of tenofovir alafenamide fumarate for preventing mother-to-child transmission of hepatitis B virus: a national cohort study.

BACKGROUND: Data on tenofovir alafenamide fumarate (TAF) for preventing mother-to-child transmission of hepatitis B virus (HBV) are lacking. AIMS: To investigate the efficacy and safety of TAF therapy for preventing hepatitis B mother-to-child transmission. METHODS: Mothers with chronic HBV infection, positive for hepatitis B e-antigen and with HBV DNA >200 000 IU/mL received TAF for preventing mother-to-child transmission were enrolled retrospectively from multiple centres with data collection on mother-infant dyads up to postpartum week 24-28. Primary measurements were the mother-to-child transmission rate and infants' malformation rate. Secondary assessments included maternal HBV DNA reduction at delivery, and maternal or infant adverse events during follow up. RESULTS: Among 71 mothers enrolled, the mean (±SD) age was 30.3 (±2.2) years. TAF was initiated during the second or third trimester and continued to delivery with a mean (±SD) duration of 12.8 (±4.0) weeks. At delivery, 85.9% (61/71) of the mothers achieved HBV DNA <200 000 IU/L. Seventy-three infants (two sets of twins) were born from mothers treated with TAF and none had congenital defects or malformations. All infants received HBV immunoglobulin and vaccine at birth with additional HBV vaccinations at one and six months. At age 24-28 weeks, all infants had negative hepatitis B surface antigen and undetectable levels of HBV DNA (<100 IU/mL). Body weight, height, and head circumferences were comparable to national standards for physical development. No severe adverse effects were reported in either mothers or infants. CONCLUSIONS: TAF for highly viraemic mothers effectively prevented mother-to-child transmission of hepatitis B. There were no safety concerns for either mothers or infants with 24-28 weeks of follow up.

Prevalence of HBV and HCV infections, Bhutan, 2017: Progress and next steps.

BACKGROUND: Bhutan is committed to eliminating hepatitis B and hepatitis C, though recent baseline estimates of disease burden in the general population are unknown. In 2017, we carried out a biomarker survey in the general population to estimate the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) biomarkers to evaluate the impact of immunization and guide further efforts. METHODS: In 2017, a cross-sectional, population-based, three-stage cluster survey was undertaken of the general population (1-17 and 20+ years of age). We visited households, collected blood specimens and administered a standard questionnaire. Specimens were collected for hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (anti-HCV) testing. We calculated prevalence of infection and selected characteristics, along with confidence intervals (CIs). RESULTS: Of 1372 individuals approached, 1358 (99%) participated. Of those, 1321 (97%) had a specimen tested for HBsAg, and among 1173 enrolled individuals 5 years of age or older, 1150 (98%) individuals were tested for anti-HCV. The prevalence of HBsAg was 2.0% in 775 persons 20 years of age or older (95% CI: 1.0-4.0) and 0.5% in 546 persons 1-17 years of age (95% CI: 0.1-1.8). The prevalence of anti-HCV was 0.3% (95% CI: 0.1-0.8) among persons ≥5 years. CONCLUSIONS: Universal hepatitis B immunization of infants has resulted in a low prevalence of chronic HBV infection in persons 1-17 years of age and the prevalence of anti-HCV is low among persons aged ≥5 years. Efforts should continue to reach high coverage of the timely birth dose along with completion of the hepatitis B vaccine series. To reduce the chronic liver disease burden among adults, HBV and HCV testing and treatment as indicated might be restricted to pregnant women, blood donors, individuals with chronic liver diseases, and other groups with history of high-risk exposures.

Maternal knowledge of the risk of vertical transmission and offspring acquisition of hepatitis B.

INTRODUCTION AND OBJECTIVES: Universal vaccination at birth and in infancy is key to the elimination of chronic hepatitis B infection. We aimed to assess hepatitis B immune-prophylaxis and perinatal transmission knowledge, in a large and ethnically diverse cohort of previously pregnant North American women, chronically infected with hepatitis B. MATERIALS AND METHODS: The Hepatitis B Research Network (HBRN) is comprised of 28 Clinical Centers in the United States and Canada. Female cohort participants were administered a questionnaire to assess: (1) their assertion of knowledge regarding HBV prophylaxis at birth, testing, and diagnosis of hepatitis B in their children, and (2) the percentage of affirmative to negative responses for each of the HBV-related interventions her child may have received. The relationship between asserted knowledge, actions taken and maternal demographics were assessed. RESULTS: A total of 351 mothers with 627 children born in or after 1992 were included. Median age at enrollment was 39.8 years. Mothers were mostly foreign-born with the largest percentage from Asia (73.4%) and Africa (11.7%). Of the 627 children, 94.5% had mothers who asserted that they knew whether their child had received HBIG or HBV vaccine at birth, for 88.8% of the children, their mothers indicated that they knew if their child was tested for HBV and for 84.5% of children, their mothers knew if the child was diagnosed with HBV infection. Among children whose mothers asserted knowledge of their HBV management, 95.3% were reported to have received HBIG or HBV vaccine, 83.4% of children were said to have been tested for HBV, and 4.8% of children were said to have been diagnosed with HBV. Younger maternal age was the only factor significantly associated with higher percentage of children for whom mothers reported knowledge of testing (p=0.02) or diagnosis of HBV (p=0.02). CONCLUSIONS: While high percentages of North American children had mothers asserting knowledge of HBV prophylaxis and testing, knowledge gaps remain, with mothers of 5.5-15.5% of children lacking knowledge of key components of the HBV prevention and diagnosis in the perinatal setting. Targeted education of HBsAg-positive mothers may aid in closing this gap and reducing vertical transmission.

Efficacy and safety of telbivudine treatment for the prevention of HBV perinatal transmission.

To observe the efficacy of telbivudine in chronic hepatitis B (CHB) women with high viral load during pregnancy and the long-term effects on intelligence, growth, and development of the newborns.A total of 87 patients were included. Forty-two patients received telbivudine orally 600 mg per day and treatment initiated from 12 weeks after gestation until the 12th postpartum week. Forty-five patients were untreated according to principle of informed consent. All infants received injection of hepatitis B immune globulin (HBIG; 200 IU) and were vaccinated with recombinant HBV vaccine. Wechsler preschool intelligence scale was used to assess mental and neuropsychological developments of these children till they were 6 years old. Data including serum HBV DNA viral load, Apgar score, and scores of Wechsler preschool intelligence scale were analyzed and compared.Levels of both serum HBV DNA and ALT in patients who received telbivudine were significantly decreased at the 12th week after delivery, compared with baseline levels (P < .01). No significant changes were observed in patients not receiving telbivudine (P > .05). Serum HBV DNA and ALT levels at the 12th week after delivery in the telbivudine group were significantly lower than those of patients without telbivudine (P < .01). The serum HBsAg-positive rate in neonates 7 months of age was 0%, which was significantly lower than that in control group (11.11%) (P < .05). No statistical differences were observed between the 2 groups regarding maternal cesarean section rate, adverse pregnancy rate, postpartum bleeding rate, neonatal body mass, Apgar score, neonatal malformation incidence, or intelligence development of newborn.Telbivudine is effective to reduce the viral load in CHB mothers with high viral load and could lower the perinatal transmission rate. Both mental and physical development in neonates with exposure to telbivudine during perinatal period were similar to those without telbivudine exposure.

Viral hepatitis in patients on hemodialysis.

Hepatitis B and hepatitis C (HCV) prevalence are higher in people on hemodialysis (HD) than the general population. Through implementation of prevention interventions including vaccines, serologic screening, and post-exposure management, transmissions linked to HD have decreased dramatically. In this manuscript, we review epidemiology of viral hepatitis, summarize current screening and vaccine recommendations, and appraise the available data about efforts to decrease incidence within HD facilities, including isolation of people with viral hepatitis within HD units. Also included is a discussion of the highly effective all-oral HCV treatment options and treatment for HCV in people awaiting kidney transplant.

"To die is better than to tell": reasons for and against disclosure of chronic hepatitis B status in Ghana.

BACKGROUND: People with a condition subject to stigmatisation, such as chronic hepatitis B, face the dilemma of whether or not to disclose their status. In Ghana, 12.3% of the adult population has the hepatitis B virus (HBV). One key strategy for breaking the cycle of hepatitis B transmission is the disclosure of hepatitis B status by people with chronic hepatitis B (PWHB). Disclosure can facilitate preventive actions to reduce hepatitis B transmission (e.g., not sharing personal items and avoiding contact with blood and body fluids). Disclosure can also motivate family members of PWHB to get tested, linked to care and clinically managed in order to reduce the progression of hepatitis B to liver cirrhosis and cancer. Given the importance of disclosure, we set out to explore reasons for and against disclosure of chronic hepatitis B status in the Greater Accra and Upper East region of Ghana. METHODS: In this exploratory qualitative study, 18 participants (10 from the Greater Accra region and 8 from the Upper East region) were recruited for semi-structured interviews. Interviews were recorded and transcribed verbatim. Data were then processed using QSR Nvivo version 10.0 and analysed for themes. RESULTS: Participants were selective disclosers, disclosing in some contexts and not in others. Reasons for non-disclosure of chronic hepatitis B status were: 1) fear of stigmatisation and 2) previous negative experiences with disclosure. Reasons for disclosure were: 1) wanting close contacts to get tested or vaccinated, 2) trusting the disclosure target(s), and 3) needing social and/or financial support. CONCLUSIONS: Our findings highlight various reasons for and against disclosure of chronic hepatitis B status in Ghana. Because anticipated, observed, and experienced stigma were important motivations for non-disclosure of chronic hepatitis B status, we recommend the development and implementation of theory and evidence-based stigma reduction interventions that are culturally appropriate, and that prioritize the participation of target populations. We also recommend the provision of counselling and support services that assist PWHB in their disclosure decision-making processes.

Assisted reproduction in hepatitis carrier couples.

Chronic Hepatitis B virus (HBV) infection is endemic worldwide, and the prevalence is especially high in the Asia-Pacific regions. Despite its high prevalence, the literature regarding the impact of HBV infection on subfertility and fertility treatment remains limited and conflicting. Latest studies do not suggest any detrimental effect of HBV infection on the outcome of IVF/ICSI treatment in women having chronic HBV infection. There is evidence that HBV exists in ovarian tissue including oocyte and follicular fluid, and therefore has the potential risk of transmission to the embryo, which can explain the finding of vertical transmission despite immunoprophylaxis. Most recently, we have observed the evidence of HBV viral replication in female HBV carriers undergoing IVF/ICSI treatment. This raises the question of whether antiviral medication should be administered during ovarian stimulation in IVF/ICSI treatment cycles for women with chronic HBV infection to help reduce the chance of vertical transmission.

Intra-host diversity of hepatitis B virus during mother-to-child transmission: the X gene may play a key role in virus survival in children after transmission.

Mother-to-child transmission of hepatitis B virus (HBV) is the main route of transmission in Asia, and characterization of HBV quasispecies is needed to further understand virus evolution and adaptation. To understand changes in HBV during mother-to-child transmission, we enrolled nine pairs of mothers and children in the study, including a set of twins. Three groups were infected with HBV genotype C, and six groups were infected with HBV genotype B. The full-length HBV genome was amplified by PCR from serum samples before antiviral treatment, the whole viral genomes from each pair were sequenced, and the complexity and diversity of the quasispecies were analyzed. The entropy of transmitted HBV in children was found to be lower than their mothers, suggesting that there was a bottleneck effect during HBV transmission from the mother to the child. Selective evolution was shown by calculating πN and πS in the whole genomes, and the highest values were obtained for the X gene, which plays a role in viral replication and immune escape. All genotype C patients and only one genotype B pair had a πN/πS greater than 1 ratio, indicating that positive selection had occurred. In addition, quasispecies were found to be different between the twin children despite having the same mother, indicating that virus evolution is host-specific.

Reasons to consider early treatment in chronic hepatitis B patients.

In spite of a decrease in the prevalence and incidence seen in recent years, chronic hepatitis B (CHB) still remains a major healthcare challenge, prevalent mostly in developing but also in developed regions. CHB is associated with significant morbidity and mortality, secondary to the complications of disease progression; cirrhosis and hepatocellular carcinoma (HCC). Historically, antiviral treatment has been restricted to patients with active hepatitis, established liver disease, fibrosis or cirrhosis and/or the risk of HCC development. As a result, patients with hepatitis B 'e' antigen (HBeAg) -positive chronic infection, formerly referred to as the 'immune tolerant' disease phase, have been excluded from treatment, since immune tolerant CHB had been considered 'benign' with no ostensible progressive liver disease. However, recent advances in 'decoding' the immunopathogenesis of CHB challenged the accuracy of this classical perception: it is now well-recognised that HBeAg-positive chronic infection is not characterized by immunological tolerance and that events associated with tumourigenesis are already present during this early disease phase. These findings have led to a paradigm shift: in 2017, the European Association for the Study of the Liver (EASL) recommended a change in the nomenclature and clinical categorisation of CHB and proposed lowering the threshold for antiviral treatment to include patients with HBeAg-positive chronic infection. It is anticipated that this could delay or even prevent disease progression and the development of HCC, alongside the potential to achieve functional cure (hepatitis B 'surface' antigen loss with or without development of hepatitis B 'surface' antibody). The current article reviews relevant literature and discusses the reasons for considering early treatment in CHB.

Efficacy of oral antiviral drugs to prevent mother-to-child transmission of hepatitis B virus: a network meta-analysis.

BACKGROUND: Hepatitis B is a serious global health problem. Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major risk factor in the endemicity of HBV infection. Oral antiviral drugs are recommended to highly viremic mothers to decrease MTCT of HBV. The present network analysis compared the efficacy of available treatments to prevent the MTCT of HBV. METHODS: The electronic databases of PubMed, Embase, Web of Science, Scopus, and Wanfang data were searched for eligible studies. Pair-wise meta-analysis and Bayesian network analysis were applied to compare the efficacy of antiviral drugs. RESULTS: Seventy-five studies involving 12,740 pregnant females were eligible for analysis. On pair-wise analysis, lamivudine (OR 0.15, 95% CI 0.09-0.25, I-squared = 0%), telbivudine (OR 0.07, 95% CI 0.05-0.10, I-squared = 0%) and tenofovir (OR 0.07, 95% CI 0.04-0.13, I-squared = 0%) significantly decreased the MTCT rate. Results of multiple comparisons with ranking probability based on Bayesian analysis showed that tenofovir (SUCRA = 96.83%) appeared more effective than the two other drugs. CONCLUSION: In addition to active and passive immunoprophylaxis, lamivudine, telbivudine and tenofovir in highly viremic mothers can further decrease MTCT of HBV. Based on direct and indirect evidence, tenofovir appears to be more effective than the two other drugs in the prevention of HBV MTCT.

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

Pregnancy Outcome of Women with Chronic Hepatitis B who Discontinued Antiviral Treatment before or in the Early Pregnancy.

Background: The aim of this study was to describe biochemical, virological features and Mother-to child-transmission (MTCT) rate in chronic hepatitis B (CHB) women who stopped antiviral therapy before or in the early pregnancy. Methods: This was a single-center, retrospective study. Forty-three CHB women who stopped treatment before or in the early pregnancy and 103 CHB women with tenofovir disoproxil fumarate (TDF) treatment throughout pregnancy were enrolled. The virological and biochemical flares during pregnancy and postpartum period were studied. MTCT rates were also compared. Results: During pregnancy, ALT flares (43.9% vs 1.0%) and viral rebound (31.7% vs 0) were more common in women who stopped treatment (P<0.001). Postpartum ALT flares were less frequent in women with treatment than those stopped treatment (0 vs 6/35, P = 0.001). The birth defect rate in the mothers who stopped treatment did not statistically differ from that of mothers treated throughout pregnancy (4.9 % vs 3.9 %, P = 1.000). There were no significant differences of gestational complications between the two groups, except intrahepatic cholestasis of pregnancy (12.2% vs 0, P = 0.002). The rate of MTCT in mothers who discontinued treatment was higher (2.4% vs 0, P = 0.285), although there was no statistically significant. Conclusion: ALT flares were common in mothers who discontinued antiviral therapy. Thus, these pregnant women should be monitored closely. Cessation of treatment was not recommended although no hepatic failure was observed. Larger studies are needed to evaluate the safety of discontinuation before pregnancy.

Integration of hepatitis B virus DNA into p21-activated kinase 3 (PAK3) gene in HepG2.2.15 cells.

Integration of HBV DNA into host chromosomes was found in most of the patients with chronic hepatitis B (CHB). In this study, using inverse nested PCR (invPCR), we found the integration site chrX: 111,009,033, which inserted into the p21-activated kinase 3 (PAK3) gene in HepG2.2.15 cells. The viral-human chimeric transcripts were also observed and, significant differences of the copy numbers of integration site chrX: 111,009,033 (P = 0.012) and intra-cell HBV DNA levels (P = 0.027) were found between the cells with and without H2O2 treatment, respectively. This study may provide a novel insight into the elucidation of etiology of HBV integration.

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.

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 mothers 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.