Faculty Bibliography
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170
Developmental Consequences of Prenatal Telbivudine Exposure during the Third Trimester
Background & Aims Fewer data exist on neuro-mental development after fetal exposure to telbivudine. We investigated the developmental consequences of infants from mothers that received telbivudine treatment for chronic hepatitis B (CHB). Methods CHB mothers with high viral load at gestational week 28 were assigned to receive either telbivudine (LdT) or usual care without antiviral therapy, based on the mothers' preference. Their infants were followed for 52 weeks to assess physical and neuro-metal development with Gesell Developmental Schedule tools. Developmental consequences were compared between the two groups. Results Among 258 mothers enrolled, 159 and 99 in the telbivudine-treated and the non-treated group, respectively. The mean duration of telbivudine therapy for the treatment group was 12.31 ± 1.02 weeks. When compared to the control group, infants at the treated-group at the age of 52 weeks had similar neuro-mental development outcomes regarding Gesell Developmental Schedule scores for gross motor (p = 0.55), fine motor (p = 0.31), adaptive (p = 0.10), linguistic (p = 0.97), and personal social (p = 0.52) domains; their physical parameters were also comparable, which included mean height (77.83±3.31 vs. 77.55±3.03 cm; p=0.51) and mean body weight (and 10.59±1.14 vs.10.57±1.19 kg; p=0.89). However, the vertical transmission rates were slightly higher in the control group (3.19% [3/94] vs. 0% [0/150]; p=0.056). Multivariate logistic regression suggested that telbivudine did not associated with negative developmental consequences. Conclusions The developmental consequences of prenatal telbivudine exposure were comparable to those without the exposure in one year observation. We now know that Telbivudine therapy is safe for hepatitis B mothers during pregnancy; ClincialTrials.gov number, NCT02301650.
PMID: 32371166
ISSN: 1542-7714
CID: 4437152
Infection and disease spectrum in individuals with household exposure to SARS-CoV-2: A family cluster cohort study
We primarily quantified exposure patterns, transmission characteristics, and the clinical spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among household contacts of individuals with severe coronavirus disease-2019 (COVID-19). We conducted a retrospective cohort study of 20 index patients hospitalized with severe COVID-19 and 79 of their household contacts. We determined the transmission frequency, range of manifestations of SARS-CoV-2 infection, and factors associated with infection in household settings. Of the 79 household contacts, 53 (67%) developed SARS-CoV-2 infection (49 [62%] symptomatic, 4 [5%] asymptomatic). Eight patients (10%) developed severe COVID-19, and one died of COVID-19 pneumonia (case-fatality rate: 1.9%). The probability of SARS-CoV-2 infection was similar in children and adults (55% vs. 72%, p = .14), with children being less likely to develop the symptomatic disease (46% vs. 68%, p = .06). Handwashing ≥ 5 times/day was associated with reduced infection risk (52.8% vs. 76.9%, p = .04). SARS-CoV-2 has a high frequency of transmission among household contacts. Nonhospitalized individuals with SARS-CoV-2 infection should be quarantined in patient care facilities rather than at home to minimize spread, if possible, and frequent handwashing should be practiced to prevent transmission.
PMID: 33538342
ISSN: 1096-9071
CID: 4802172
Genome-wide analysis identifies novel susceptibility loci for myocardial infarction
AIMS:While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. METHODS AND RESULTS:We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. CONCLUSIONS:A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.
PMID: 33532862
ISSN: 1522-9645
CID: 4920802
Serum IL-21 levels predict HBeAg decline during rescue therapy in patients with partial response to nucleos(t)ide analogues
To investigate whether IL-21 levels predict treatment outcomes of salvage therapy among patients with suboptimal response (SOR) to nucleos(t)ide analogues (NAs), serum IL-21 levels were measured in a prospective cohort of hepatitis B e antigen (HBeAg)-positive patients with SOR to antiviral therapy. The patients switched therapy to entecavir (ETV) with or without adefovir (ADV) for 104 weeks. IL-21 levels at treatment week 12 in patients who achieved HBeAg loss with undetectable levels of hepatitis B virus (HBV)-DNA at week 104 were the primary endpoint and the results were compared with those of corresponding patients without such an endpoint. Furthermore, IL-21 levels at treatment week 12 in patients who achieved an HBeAg-level decline at week 104 were assessed as the secondary endpoint. Among 24 enrolled patients with SOR to ADV (n=21), telbivudine (n=2) or ETV (n=1), the median (10-90th percentile) levels of HBeAg, HBV-DNA and ALT at baseline were 2.7 (0.2-3.1) log10 S/CO, 5.2 (3.5-7.5) log10 IU/ml and 0.9 (0.5-3.1) upper limit of normal, respectively. Comparison of the patients with and without HBeAg loss at week 104 indicated that their mean IL-21 levels did not significantly differ at week 12 (63.0±14.4 vs. 55.9±10.5 pg/ml; P=0.26). In the secondary endpoint analyses of patients with and without HBeAg level decline, the elevated levels of IL-21 at the first 12 weeks were significantly higher in the decline group (15.6±8.3 vs. 3.1±13.2 pg/ml; P=0.03). Following adjustment for confounding factors, the elevated levels of IL-21 from baseline to week 12 independently predicted an HBeAg level decline at week 104 (odds ratio=1.137, R2=0.23; P=0.047). In conclusion, the serum IL-21 levels at the first 12 weeks during the salvage therapy independently predicted HBeAg level decline at treatment week 104 in patients with SOR to NAs (ClinicalTrials.gov identifier: NCT01829685; date of registration, April 2013).
PMCID:7818553
PMID: 33500704
ISSN: 1792-0981
CID: 5113132
The clinical course and management of cervical cancer with splenic metastasis: Case report and review of the literature [Case Report]
Adenovirus-mediated herpes simplex virus thymidine kinase gene therapy (ADV-TK) in combination with interventional treatment could relieve the symptoms in patients with widespread splenic metastasis.
PMCID:7869355
PMID: 33598227
ISSN: 2050-0904
CID: 4802272
The case for simplifying and using absolute targets for viral hepatitis elimination goals
The 69th World Health Assembly endorsed the Global Health Sector Strategy for Viral Hepatitis, embracing a goal to eliminate hepatitis infection as a public health threat by 2030. This was followed by the World Health Organization's (WHO) global targets for the care and management of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. These announcements and targets were important in raising awareness and calling for action; however, tracking countries' progress towards these elimination goals has provided insights to the limitations of these targets. The existing targets compare a country's progress relative to its 2015 values, penalizing countries who started their programmes prior to 2015, countries with a young population, or countries with a low prevalence. We recommend that (1) WHO simplify the hepatitis elimination targets, (2) change to absolute targets and (3) allow countries to achieve these disease targets with their own service coverage initiatives that will have the maximum impact. The recommended targets are as follows: reduce HCV new chronic cases to ≤5 per 100 000, reduce HBV prevalence among 1-year-olds to ≤0.1%, reduce HBV and HCV mortality to ≤5 per 100 000, and demonstrate HBV and HCV year-to-year decrease in new HCV- and HBV-related HCC cases. The objective of our recommendations is not to lower expectations or diminish the hepatitis elimination standards, but to provide clearer targets that recognize the past and current elimination efforts by countries, help measure progress towards true elimination, and motivate other countries to follow suit.
PMID: 32979881
ISSN: 1365-2893
CID: 4679282
The Characteristics of Natural Killer Cells in Chronic Hepatitis B Patients Who Received PEGylated-Interferon versus Entecavir Therapy
Background/UNASSIGNED:To explore the role of natural killer (NK) cells in the process of hepatitis B virus (HBV) clearance and whether their phenotype is related to antiviral treatment outcome in chronic hepatitis B (CHB) patients. Method/UNASSIGNED:NK cells and mean fluorescence intensity (MFI) of receptors NKp46 and IFNAR2 on the surface of NK cells were measured. Subgroup analyses were performed by comparing treatment responders versus nonresponders with aforementioned parameters in each group. Results/UNASSIGNED:NK frequency and IFNAR2 MFI significantly decreased at 12 and 24 weeks from baseline. Conclusions/UNASSIGNED:treatment significantly enhanced NK cell frequency and function when compared to entacavir. Positive treatment responses to either interferon or entecavir were associated with NK cell function improvement. This trial is registered with clinical trial registration no. NCT03208998.
PMCID:7857883
PMID: 33575322
ISSN: 2314-6141
CID: 4799822
Antiviral kinetics of tenofovir alafenamide and tenofovir disoproxil fumarate over 24 weeks in women of childbearing potential with chronic HBV
BACKGROUND/PURPOSE/OBJECTIVE:Use of tenofovir disoproxil fumarate (TDF) improves patient outcomes in preventing mother-to-child transmission (pMTCT) of the hepatitis B virus (HBV) in mothers with chronic HBV and high viral loads. Given the lack of data for tenofovir alafenamide (TAF) in pMTCT, rates of early viral suppression with TAF and TDF were evaluated in women of childbearing potential (WOCBP) participating in 2 randomized, double-blind, Phase 3 studies in chronic HBV. METHODS:In a patient subset meeting WOCBP criteria and with baseline HBV DNA >200,000 IU/mL, rates of viral suppression with TAF or TDF in achieving the target of HBV DNA <200,000 IU/mL at weeks 12 and 24 were assessed. Multivariate logistic regression was used to identify factors predictive of failure to suppress HBV DNA to the target level. RESULTS:In 275 of 1298 (21%) patients meeting WOCBP criteria with high viral load, 93% and 96% had HBV DNA <200,000 IU/mL at weeks 12 and 24, respectively. Results for TAF (n = 194) vs TDF (n = 81) treatment were similar at weeks 12 and 24 (94% vs. 90% and 97% vs. 93%), respectively. High baseline HBV DNA level, genotype D infection, and prior interferon (week 24 only) were predictive of failure to achieve the target level. Both treatments were well tolerated with TAF showing less impact on renal and bone parameters. CONCLUSIONS:In WOCBP with high VL, no differences were found between TAF and TDF in reducing HBV DNA to levels associated with lower transmission risk. These data support ongoing studies of TAF for pMTCT.
PMID: 33984038
ISSN: 1932-6203
CID: 4878452
EFFICACY AND SAFETY OF SOFOSBUVIR-BASED REGIMENS IN HEPATITIS C PATIENTS WITH DECOMPENSATED CIRRHOSIS: A SYSTEM REVIEW AND META-ANALYSIS [Meeting Abstract]
ISI:000707188003034
ISSN: 0270-9139
CID: 5074112
The safety of antiviral therapy and drug withdrawal for the prevention of mother-to-child transmission of HBV during pregnancy
BACKGROUND AND AIM/OBJECTIVE:The efficacy of prenatal antiviral therapy (AVT) for preventing the vertical transmission of hepatitis B virus (HBV) is well demonstrated. However, data are limited regarding the safety of postpartum cessation of AVT, which may induce alanine aminotransferase (ALT) elevation. We aimed to investigate the necessity of prolonging maternal AVT after delivery. METHODS:IU/ml were prospectively enrolled and received AVT during the third trimester until delivery. Patients were offered to discontinue AVT either at delivery or postpartum week (PPW) 6. In addition, mothers who deferred AVT during pregnancy served as the control group. All mothers were followed until postpartum week 52 for clinical and virological parameters of hepatitis flares. RESULTS:Among 118 mothers recruited, 91 received AVT with 53 (group A) and 24 (group B) discontinue their treatment at delivery and postpartum week 6, respectively. Twenty-seven mothers who deferred AVT during pregnancy were followed as the control (group C). Of 104/118 mothers who completed the study, 50% (52/104) had postpartum elevated ALT levels, which were mild and moderate except 6/104 (5.77%) of patients had levels > 5 times the upper limit of normal. 70% (36/52) of the ALT flares occurred within 12 weeks after delivery. In subgroup analyses, the freuquency of ALT elevation were similar among the groups A vs. B vs. C [50.9% (27/53) vs. 58.3% (14/24) vs 40.7% (11/27), respectively; P = 0.447], as well as the mean peak ALT level (108.4 / 74.1 / 126.7 U/L in groups A/B/C, respectively; P = 0.291). CONCLUSIONS:Although postpartum ALT flares were common for mothers with or without AVT during pregnancy, most cases of ALT elevation were mild to moderate. Our study observed that extending AVT to postpartum week 6 did not affect maternal outcomes and ATV should be discontinued at birth. Close monitoring is warrant as severe flares rarely occurred. ClinicalTrials.gov number: NCT03468907. This article is protected by copyright. All rights reserved.
PMID: 32410298
ISSN: 1096-9071
CID: 4438272
