LdT Group Research Articles

Comparison of the efficacy and safety of TAF, TDF, and LdT to prevent the transmission of hepatitis B in pregnant women: A retrospective study.

To compare the efficacy and safety of telbivudine (LdT), tenofovir alafenamide fumarate (TAF), and tenofovir disoproxil fumarate (TDF) for preventing hepatitis B transmission in immune-tolerant pregnant women with HBV infection. We conducted a retrospective cohort study involving women who had hepatitis B virus deoxyribonucleic acid (HBV DNA) ≥ 2 × 105 IU/mLand initiated LdT, TDF, or TAF to prevent mother-to-child transmission (MTCT). The primary endpoint was the safety of mothers and infants. The secondary endpoints were maternal HBV DNAreduction at delivery and MTCT rate. A total of 96 patients were enrolled in the study (LdT group, n = 36; TDF group, n = 35; TAF group, n = 25). All infants received hepatitis B virus immunoprophylaxis. The MTCT rate was 0%([0 of 25] vs. [0 of 35] vs. [0 of 36], p > .05). No severe liver function damage occurred in any of the mothers. Babies delivered in all groups had prenatal ultrasound screening abnormalities, but abnormality rates were not statistically significant between groups. The application of TDF, TAF, or LdT to immune-tolerant HBV-infected pregnant women in middle-late pregnancycan successfully interrupt MTCT of the HBV virus. However, for all three groups of pregnant women who delivered babies with abnormal prenatal ultrasound screening, an expanded sample size may be needed for further observation.

The molecular feature of abnormal fetal neuromuscular development after maternal use of telbivudine or tenofovir during pregnancy in rodent model

AimsMaternal treatment with nucleoside analogues such as telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) has been applied worldwide. However, administration of LdT or TDF during pregnancy may affect the fetal neuromuscular development. We conducted the current study to investigate the histological pathology and transcriptomic changes pertaining to the neuromuscular system of the newborn exposed to LdT or TDF during pregnancy in rodent model. Main methodsPregnant C57/BL6 mice were randomly divided into three arms and administered either with LdT solution (0.1 ml, 78 mg/kg/d), TDF solution (0.1 ml, 39 mg/kg/d) or normal saline solution (0.1 ml). Pups in each arm were weighed and sacrificed after birth. Both sides of quadriceps femoris muscle of the newborn were obtained. The histological observation was conducted under light microscope. The transcriptional profiling was analyzed with RNA sequencing (RNA seq). Key findingsFour types of morphological abnormalities of the newborn neuromuscular system, being clusters of rhabdomyoblasts, skeletal muscle fibrosis, rhabdomyolysis and necrosis and immature muscle fiber bundles, were noted in both LdT group and TDF group. Moreover, both groups showed significantly decreased gross cross-sectional area of muscle fiber and significantly increased percentage of muscle lesion area. RNA seq identified a total of 164 differentially expressed genes (DEGs) essential to fetal neuromuscular development. These DEGs were involved in calcium regulation, phospholipid activity, muscle cell development, the functioning of mitochondria/endoplasmic reticulum/lysosome/cytoskeleton, the regulation of arachidonic acid and the development of nervous system. SignificanceOur findings suggest maternal administration of LdT or TDF lead to abnormal neuromuscular development in offspring mice. Further study should be encouraged to investigate the down-stream signaling pathways.

Short versus long course therapy in the treatment of febrile urinary tract infections in men based on serum PSA values

BackgroundFebrile urinary tract infections (fUTI) in men are frequently complicated with subclinical prostatic involvement, measured by a transient increase in serum prostate-specific-antigen (sPSA). The aim of this study was to evaluate recurrence rates in a 6-month follow-up period of 2-week versus 4-week antibiotic treatment in men with fUTI, based on prostatic involvement. Clinical and microbiological cure rates at the end-of-therapy (EoT) were also assessed. MethodsOpen label, not-controlled, prospective study. Consecutive men diagnosed of fUTI were included. Duration of therapy was 2 weeks for patients with a sPSA level <5mg/L (short duration therapy, SDT) or 4 weeks for PSA >5 mg/L (long duration therapy, LDT). ResultsNinety-one patients were included; 19 (20%) received SDT. Median age was 56.9 years (range 23-88). Bacteremia was present in 9.8% of patients (Escherichia coli was isolated in 91%). Both groups had similar demographic, clinical characteristics and laboratory findings. Median PSA levels were 2.3 mg/L in the SDT group vs 23.4 mg/L in the LDT group. In the 6-month visit, 26% of patients had achieved complete follow-up. Nonsignificant differences between groups were found neither in recurrence rates after 6 months (9% in SDT vs 10% in LDT) nor in clinical or microbiological cure rates at EoT (100% in SDT vs 95% in LDT and 95% in SDT vs 93% in LDT respectively). ConclusionsOne fifth of men with fUTI did not present apparent prostatic involvement. A 2-week regimen seems adequate in terms of clinical, microbiological cure and recurrence rates for those patients without PSA elevation.

Comparison of tenofovir disoproxil fumarate and telbivudine in preventing hepatitis B transmission in mothers with high viral load.

To add to the limited data that exist on the selection of drugs to prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV). This is a prospective cohort study that enrolled mothers with HBV-DNA ≥2× 105 IU/ml. All enrolled mothers received either tenofovir disoproxil fumarate (TDF) or telbivudine (LdT) to prevent HBV transmission. A total of 270 mothers received TDF treatment and 275 mothers received LdT treatment. The predelivery decline in HBV-DNA in the TDF group was higher than the LdT group (3.92 ± 0.93 log IU/ml vs. 3.76 ± 0.94 log IU/ml, P= 0.043). In the primary analysis, the MTCT rate of the TDF group was comparable to that of the LdT group, both in the intention-to-treat analysis (1.5% [4/275] vs. 1.8% [5/273], P> 0.99) and the per-protocol analysis (0% in both groups, P> 0.99). The alanine aminotransferase elevation rates in the TDF group were lower than in the LdT group (17.3% vs. 27.4%, P= 0.005). Less anorexia and more arthralgia were observed in the LdT group than the TDF group. TDF and LdT are both effective in preventing MTCT of HBV, but they may cause different adverse events. TDF is more effective in reducing HBV viral load and had fewer alanine aminotransferase abnormalities than LdT.

Efficacy and safety of tenofovir disoproxil fumarate or telbivudine used throughout pregnancy for the prevention of mother-to-child transmission of hepatitis B virus: A cohort study

ObjectiveTenofovir disoproxil fumarate (TDF) use compared with telbivudine (LdT) use throughout pregnancy has not been adequately investigated. To compare the efficacy and safety of TDF and LdT for the prevention of mother-to-child transmission (MTCT) of hepatitis B from highly viremic mothers throughout pregnancy in real-world settings. Study designThis was a single-center, retrospective cohort study. From January 1, 2013, to December 31, 2018, we retrospectively enrolled 602 mothers with chronic hepatitis B (CHB) who received antiviral treatment throughout pregnancy at Beijing Ditan Hospital. A total of 562 mothers met the inclusion criteria, with 167 in the TDF group and 395 in the LdT group. Mothers and infants were followed for 28 weeks postpartum. The primary endpoint was the MTCT rate of HBV. The secondary endpoints were the safety profiles in mothers and infants. ResultsThe MTCT rates were 0 % in both the TDF and LdT groups. The rates of neonatal congenital abnormalities were similar between the TDF and LdT groups (1.2 % vs 1.8 %, P = 0.896). There were no significant differences in perinatal complications between the two groups (all P > 0.05). There were also no significant differences in gestational age or infant height, weight, Apgar score. The level of HBV DNA at 28 weeks postpartum was an independent risk factor for postpartum alanine aminotransferase (ALT) flares (OR = 2.348, 95 % CI: 1.100–5.016, P = 0.027). ConclusionTDF and LdT treatments throughout pregnancy in mothers with CHB were equally effective in preventing MTCT and safe.

Long-term follow-up of treatment-naïve HBeAg-negative patients with chronic hepatitis B.

We aimed to explore long-term results of oral antiviral agents in treatment-naïve "HBeAg negative chronic hepatitis B (CHB)" and determine the factors affecting the complete virological response. Patients with HBeAg-negative CHB who used oral antiviral agents for at least 3years were evaluated retrospectively. A total of 173 patients were recorded. The mean duration of treatment was 62.2 ± 28.9months. Complete virological responses (CVR) were 82.8% (n = 53/64) in tenofovir disoproxil fumarate (TDF), 84.4% (n = 49/58) in lamivudine (LAM), 83.9% (n = 26/31) in entecavir (ETV), 95% in telbivudine (LdT) (n = 19/20) (p = 0.290). Multivariate analysis revealed age ≤ 40 (p = 0.012, 95%CI = 1.38-13.76, OR = 4.36) and baseline HBV DNA value (p = 0.003, 95%CI = 1.23-2.63, OR = 1.78) as independent factors for CVR. Virological breakthrough was detected in 29 (50%) patients on LAM therapy, two (6.4%) patients on ETV therapy, and two (10%) patients on LdT therapy. Treatment was switched to another antiviral agent due to osteoporosis in four patients in the TDF group, muscle pain in nine patients in the LDT group, and headache in one patient in the ETV group. Hepatocelluler cancer was detected in five patients. HBsAg seroclearance developed in two patients. Anti-HBs seroconversion was not detected. CVR was achieved at similar rates with all four antiviral agents, while younger age (≤ 40) and low baseline viral load were the main factors for virological response. However, drug resistance and virological breakthrough in the LAM group and side effects in the LdT group were detected during the long-term follow-up. Moreover, HBsAg seroclearance was achieved at very low rates with oral antiviral agents.

Infant immune response to hepatitis B vaccine after fetal exposure to telbivudine

ABSTRACT Whether telbivudine (LdT) treatment to pregnant women with hepatitis B surface antigen (HBsAg) affects infant immune response to hepatitis B vaccine (HepB) has not been investigated. A total of 127 HBsAg positive mothers and their neonates were enrolled and followed up at 11–13 months. Mothers took LdT (LdT group) or did not receive antiviral therapy (control group). Infant anti-HBs, immune cells and cytokines were measured after HepB was administered according to 0-1-6 procedure. We performed a 1:3 propensity score matching (PSM). Immune indexes in the two groups were compared. Baseline characteristics of mother-baby pairs were comparable in LdT group and control group. Infant anti-HBs geometric mean concentration (GMC) did not differ significantly between the two groups [767.70 (745.35) vs. 711.90 (819.60), P = .599]. There was no difference between the two groups in infant positive rate of anti-HBs [97.8% (91/93) vs. 97.1% (33/34), P = .999] and strong positive rate of anti-HBs [40.9% (38/93) vs. 44.1% (15/34), P = .742]. Infants with negative, low, medium, and high anti-HBs levels were similarly distributed between the two groups (P = .511). No differences in proportion of helper T cells, cytotoxic T cells, B cells, myeloid dendritic cells, and plasmacytoid dendritic cells of infants (P > .05) were detected between the two groups. Children in the LdT and control group had comparable levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, interleukin-12, interferon-α, interferon-γ and tumor necrosis factor-α (P > .05). Intrauterine exposure to LdT was safe to infant immune response to HepB after birth.

Developmental consequences of children born from mothers with telbivudine treatment during late pregnancy: A prospective study with 3-year follow-up

ABSTRACT We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant’s development in gross motor (OR 6.49, 95% CI 1.37–30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05–0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation. Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin.

Analysis of long-term safety and efficacy of nucleos(t)ide analogue therapy for chronic hepatitis B throughout pregnancy

BackgroundLimited data exist regarding the efficacy and long-term safety of nucleos(t)ide analogue therapy throughout pregnancy for women with chronic hepatitis B and their children. MethodsThis retrospective cohort study included 165 women in total: 91 women received telbivudine (LDT) and 74 women received tenofovir (TDF) throughout pregnancy. The virological response and safety in women were recorded, and the physical development and bone mineral density in children were evaluated up to 5 years of age. ResultsThe rate of virological breakthrough in women was 4.24% overall (7.70% in LDT group and 0% in TDF group; P < 0.05). No cases of renal injury or other obstetric adverse events occurred in either group of women. Among the children, only one child had a significantly low Z score for weight for age (<-2), and no children had a significantly low Z score for height for age or bone mineral density. No significant difference was found between the children in the two groups. ConclusionsNucleos(t)ide analogue therapy with TDF or LDT throughout pregnancy had no effect on the long-term physical development and bone development of children. In addition, the use of TDF throughout pregnancy had better long-term antiviral efficacy than LDT in women, with no evidence of renal toxicity.

Developmental Consequences of Children Born from Mothers with Telbivudine Treatment During Late Pregnancy: A Prospective Study with 3-Year Follow-Up

Aims: We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Methods: Mothers with high HBV load were assigned to either LdT group (n=81, 600 mg of LdT each day from gestational week 28 to delivery) or control group (n=39, untreated). Their infants were followed for 36 months to assess physical and neurological development with Gesell Developmental Schedule (GDS) tools. Results: At 12 months after birth, the mean scores in LdT group for gross motor, fine motor, adaptive, linguistic and personal social domains were similar to those in control group. At 36 months, infants in LdT group had higher mean score for gross motor than control group (98.42±9.69 vs 94.54±7.48, p=0.03). In LdT group, the rates of normal development were higher for gross motor (96.30% vs 82.05% p=0.01) and lower for adaptive (74.07% vs 92.31% p=0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant’s development in gross motor (OR 6.49, 95% CI 1.37-30.20, p=0.02) and adaptive (OR 0.18, 95% CI 0.05-0.71, p=0.01) at 36 months. Conclusions: Prenatal LdT exposure might affect neurological development in long-term observation. Trial Registration: The study was registered at clinicaltrials.gov (Clinical Trials. gov ID: NCT02301650). Funding Statement: This study was funded in part by the Beijing Municipal Science & Technology Commission [No. Z151100004015122], in part by the Beijing Municipal Administration of Hospitals Clinical medicine Development of special funding support [No.XMLX 201706], in part by the National Science and Technology Major Project of China [No.2017ZX10201201-001-006, No.2017ZX10201201-002-006, and 2018ZX10715-005-003-005)], in part by Beijing Science and Technology Commission [No. D161100002716002], in part by the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority [No.XXZ0302 and XXT28]. Declaration of Interests: No potential conflict of interest relevant to this article was reported. Ethics Approval Statement: The study was approved by the Institutional Review Board of Beijing Ditan Hospital (Approval number: JDL2014-076-01). Written informed consents were obtained from all participants.

Efficacy and Safety of Lamivudine or Telbivudine in Preventing Mother-to-Child Transmission of Hepatitis B Virus: A Real-World Study.

Background There are few large sample studies evaluating the safety and efficacy of lamivudine (LAM) or telbivudine (LdT) in preventing hepatitis B mother-to-child transmission (MTCT) in highly viremic mothers in the third trimester of pregnancy in real-world settings. The purpose of this study was to analyze a large sample size of HBV-infected mothers to better understand the safety and efficacy of LAM and LdT under the aforementioned criteria. Methods During the period of November 2008 to November 2017, we retrospectively enrolled mothers with HBV DNA > 1 × 106 IU/mL who received LAM or LdT during the third trimester of pregnancy and compared them to untreated mothers. All mothers were divided into the three following groups: the LAM group, the LdT group, and the control group. Results A total of 2624 HBV-infected mothers were enrolled in the study, with 363 in the LAM group, 1283 in the LdT group, and 978 in the control group. The MTCT rates were significantly lower in the LAM or LdT group than that in the control group (0.4% or 0.3% versus 9.0%, P < 0.001). Infants born to untreated mothers had a significantly higher risk of HBV infection (OR = 28.6, 95% CI: 10.4–78.7, P < 0.001). There were no significant differences in perinatal complications between the three groups (P > 0.05). There were also no differences for gestational age or infants' height, weight, Apgar scores, or birth defect rates. Postpartum discontinuation of antiviral therapy did not seem to increase the risk of postpartum alanine aminotransferase (ALT) flare. Conclusion LAM or LdT treatment initiated in the third trimester for mothers with HBV DNA > 1 × 106 IU/mL was equally safe and effective in preventing MTCT.

Efficacy and safety of telbivudine and tenofovir disoproxil fumarate in preventing hepatitis B vertical transmission: A real-life practice.

Mother-to-child transmission (MTCT) is a major obstacle in the elimination of hepatitis B virus (HBV) infection. Telbivudine (LdT) and tenofovir disoproxil fumarate (TDF) are the two most common antiviral medicines for preventing MTCT. However, the efficacy and safety of LdT and TDF in preventing HBV vertical transmission during the second to third trimester have not been compared rigorously. Therefore, we carried out a prospective multicentre cohort study of chronic hepatitis B in mothers with HBV DNA>106 IU/mL, receiving LdT or TDF during the second to third trimester. Among the 893 mothers enrolled, 857 (LdT/TDF/untreated group (NTx)=396/325/136) completed consecutive follow-up with 854 infants (LdT/TDF/NTx=395/323/136). LdT and TDF treatment resulted in a similar decrease of HBV DNA in mothers at delivery. Multivariate analysis indicated that only HBsAg titre at the baseline correlated with viral DNA decrease (P=0.015). With intention-to-treat analysis, MTCT rates in the LdT, TDF and NTx group were 4.41%, 2.42% and 22.08%, respectively. An increasing vertical transmission rate was found to be closely associated with higher HBsAg titre,5.32% and 17.65% infection rate was estimated in infants born to mothers with HBsAg>4 and >5 log10 IU/mL, respectively. No serious side effects were reported in either mothers or infants. LdT and TDF treatments were well tolerated and showed comparable efficacy in reducing MTCT. Higher risk of MTCT was shown in pregnant women with HBsAg>4 log10 IU/mL.

Impact of cessation of antiviral therapy at delivery on postpartum liver function in mothers with chronic hepatitis B virus infection

Objective: To investigate the impact of immediate cessation of antiviral therapy on postpartum liver function and the factors influencing postpartum abnormality in mothers with chronic hepatitis B virus infection. Methods: A retrospective cohort study was conducted. One hundred eighty-eight pregnant women with HBV DNA level > 2×106 IU/ml were enrolled from June 2014 to June 2018. Demographic information and clinical data of liver function and HBV DNA load during gravidity, intrapartum and postpartum period were collected. According to the antiviral treatment recommendations during pregnancy, the women were divided into three groups, namely, tenofovir (TDF), telbivudine (LdT) and control group. Liver function abnormalities among the three groups were compared within 6 months after delivery, and the factors influencing abnormal liver function were analyzed by unconditional logistic regression. Results: Of the 188 cases, 72 cases were in the TDF group, 80 cases in the LdT group, and 36 cases in the control group. Pregnant women in the TDF and LdT groups received oral TDF (300 mg/d) and LdT (600 mg/d) from 28 ± 4 weeks of gestation till delivery. Among the 188 patients, 30 (16.0%) had abnormal postpartum liver function abnormality. The incidence of postpartum liver function abnormality [alanine aminotransferase (ALT) > 2 × upper limit of normal (ULN)] in the TDF, LdT, and control groups was 19.4%, 12.5%, and 16.7%, respectively. The postpartum peak levels of ALT (median, range) in the three groups were 34.5 (12.0-946.0) U/L, 37.5 (12.0-733.8) U/L, and 39.0 (7.0-513.0) U/L, respectively. There was no significant difference between the two indexes among the three groups (P > 0.05). There was no statistically significant difference in the degree of postpartum liver function abnormalities between the three groups (P = 0.944). Most of the liver function abnormalities were mild to moderate (2 × ULN≤ALT < 10 × ULN), and usually resolved spontaneously or by treatment. Univariate and multivariate analysis showed that baseline ALT level during pregnancy was an independent factor associated with postpartum liver function abnormality (OR = 1.031, CI 95%: 1.005-1.058; χ(2) = 5.340, P = 0.021), whereas age, antiviral therapy, HBeAg-positivity, baseline HBV DNA levels, gravidity, parity, preterm delivery and delivery mode were not significantly associated with postpartum liver function abnormality. Conclusion: Cessation of antiviral therapy after delivery did not significantly increase the risk of postpartum liver function abnormality in pregnant women with chronic HBV infection. The ALT level during pregnancy is a factor influencing postpartum liver function abnormality.

Clinical study on blocking mother-to-child transmission of hepatitis B virus with high viral load and HBeAg positivity during pregnancy in Guizhou province

Objective: To observe the efficacy and safety related measures by blocking mother-to-child transmission of hepatitis B virus with high viral load and HBeAg positivity during pregnancy in Guizhou province. Methods: Outpatient and inpatient cases of the Department of Infectious Diseases and Obstetrics of Guizhou Medical University Affiliated Hospitals from May 2016 to July 2017 were retrospectively divided into intervention group, non-intervention group and non- hepatitis B pregnant women group; with 75 cases in each group. HBsAg and HBeAg were positive in the intervention group. Pregnant women with HBV DNA ≥10(6) IU/ml were treated with anti-HBV therapy for 24 to 28 weeks of gestation until delivery. According to oral drugs, they were divided into tenofovir (TDF) group or telbivudine (LDT) group, non-intervention group (HBsAg and HBeAg positive), HBV DNA positive pregnant women, pregnant women with no anti-HBV drugs, non-hepatitis B pregnant women (normal pregnant women without HBV infection). Infants and young children born to the three groups of women were immunized with the national viral hepatitis B action plan. The gestational weeks and Apgar scores at birth, delivery mode, feeding mode, sex and 7-months-old age were observed and counted. Serum hepatitis B markers (HBVM) and HBV DNA were quantitatively detected. HBVM was detected by time-resolved fluorescence immunoassay (TRFIA), and HBV DNA was detected by real-time PCR (FQ-PCR). The changes of liver parameters, HBsAg, HBeAg, HBV DNA, adverse drug reactions and treatment response of pregnant intervention group before medication (12-24 weeks of gestation), 4 weeks of medication (28-32 weeks of gestation), 36-40 weeks of gestation (36-40 weeks of gestation) were statistically calculated. A t-test was used to compare the data between the measurements. Data measurements within the groups were analyzed using rank -sum test. Results: In the intervention group, therapeutic medications showed no differences in demographic and clinical characteristics between TDF group and LDT group, including liver parameters, HBsAg, HBeAg and log10HBV DNA level. Compared with pre-treatment (TDF group: 4.84 ± 2.01; LDT group: 5.08 ± 1.99), TDF and LDT were significantly lower at the end of pregnancy (TDF group: 3.06 ± 0.66; LDT group: 3.51 ± 1.20). P < 0.05); and the treatment response rate was 100%. There were no serious adverse events in the intervention group. Infants and young children (7-months-old) in the intervention group had negative HBsAg, HBeAg and HBV DNA. The mother-to-child transmission rate of HBV was zero, with blocking rate of 100%. In addition, both infants and young children had different degrees of hepatitis B protective antibodies (anti-HBs, M: 144.33), and their antibody titers were higher than that of non-intervention group (anti-HBs, M: 65.91) and non-hepatitis B pregnant women (anti-HBs, M: 58.43). The difference was statistically significant (P < 0.05), and there was no significant correlation between the use of antiviral and the way of delivery and feeding. Outcomes of mother-to-child transmission of HBV infection in infants and young children (7-months-old) delivered by three groups of pregnant women in the non-intervention groups had 20.0% (15/75)/ 17.3% (13/75) HBsAg/HBeAg positivity rate, and 17.3% (13/75) HBV DNA positivity rate. Overall, mother-to-child transmission rate of HBV infection was 20% (15/75). Furthermore, the relationship between mother's HBV DNA load and infant HBV infection in the non-intervention group showed mother's HBV DNA ≥10(6) IU/ml. Conclusion: In the non-intervention group, mother-to-child transmission of HBV occurred, and infected mothers HBV DNA was ≥106 IU/ml before delivery. This suggests that HBeAg positive and high load HBV DNA replication were independent risk factors for mother-to-child transmission of hepatitis B. Therefore, prenatal drug intervention and postpartum standard immune blockade are necessary for high-risk pregnant women with hepatitis B to achieve zero mother-to-child transmission of hepatitis B in real- clinical practice.

Effects of tenofovir and telbivudine on HBV RNA in pregnant women with different genotypes of HBeAg-positive hepatitis B in Guizhou Province

Objective: To investigate whether HBV genotype influences HBV DNA and RNA responses to tenofovir(TDF) and telbivudine(LDT) in pregnant women with HBeAg-positive in Guizhou. Methods: This was a retrospective analysis of 75 pregnant women hepatitis B with HBsAg and HBeAg double-positive(19-38 years old, median age 26 years old), who were enrolled in the Department of Infectious Diseases and Obstetrics Clinic of the Affiliated Hospital of Guizhou Medical University from May 2016 to July 2017.Blood samples were collected at 12-24, 28-32 and 36-40 weeks of pregnancy for analyses of genotype, including hepatitis B surface antigen(HBsAg), hepatitis B e antigen (HBeAg), HBV DNA, HBV RNA and liver function, alanine transaminase(ALT), aspartate transaminase(AST), total bilirubin(TBiL), total bile acids(TBA), cholinesterase(CHE), alkaline phosphatase (ALP). Continuous variable was adopted by means of mean±standard deviation, and categorical variables were used for statistical analysis. Results: The HBV genotype was B in 64.0%(48/75)and C in 36.0%(27/75). The TDF and LDT groups showed no differences in demographic and clinical characteristics, including liver function tests, HBsAg, HBeAg, log(10)HBV DNA and log(10)HBV RNA.TDF groups, pre-treatment: HBV DNA (4.8±2.0), HBV RNA (6.4±1.1); at 4 weeks of treatment: HBV DNA (4.0±0.8), HBV RNA (6.0±0.9); at the end of treatment: HBV DNA (3.1±0.7), HBV RNA (5.5±0.8). LDT groups, pre-treatment HBV DNA (5.1±2.0), HBV RNA(6.5±0.9); at 4 weeks of treatment: HBV DNA (4.4±1.2), HBV RNA(6.5±0.8); at the end of treatment: HBV DNA(3.5±1.2), HBV RNA (6.1±0.7). Compared with pre-treatment (12-24 weeks), the TDF and LDT group showed significant reductions in log(10)(HBV DNA) and log(10)(HBV RNA) at 36-40 weeks ( P<0.05). Under the influence of excluding other variables, the genotype had a certain influence on the HBV RNA load.That was, HBV RNA in patients with the C genome decreased by 0.54 units(log(10)) at the end of the treatment compared to patients with the B genome, and the P value was less than 0.05. Conclusion: B and C genotypes are predominant in pregnant women with hepatitis B in Guizhou Province. B-type viruses are more easily controlled when different genotypes are treated with nucleotide analogues.

Compare the effect of combined therapy between telbivudine plus adefovir dipivoxil and lamivudine plus adefovir dipivoxil corresponding to renal function in patients with hepatitis B virus infection

Objective: To compare the effect of combined therapy using lamivudine (LAM) plus adefovir (ADV) versus telbivudine (LdT) plus adefovir corresponding to the renal function of CHB patients. Methods: A total of 120 patients with chronic hepatitis B were enrolled. According to single daily dosing, they were divided into 4 groups: LdT + ADV group (n = 32), ADV+LdT group (n = 28), LAM + ADV group (n = 38) and ADV + LAM group (n = 22). Hepatorenal function, HBV serological markers, HBV DNA quantification, creatine kinase (CK) and other parameters were examined every 3 months. Serum alanine aminotransferase (ALT) normalization rate, undetectable HBV DNA rate, hepatitis B e antigen (HBeAg) seroconversion rate, level of serum creatinine (CR) and estimated glomerular filtration rate (eGFR) were analyzed at baseline time, and at weeks 24 and 52.Stastical data were analyzed by t- test and analysis of variance, count data using χ (2) test. Results: There was no statistically significant difference between the four groups in terms of ALT normalization rate, HBeAg seroconversion rate, undetectable HBV DNA rate at 24 and 52 weeks. Compared with baseline, at 24 weeks of treatment, there was no significant change in serum creatinine and eGFR in the 4 groups, but after 52 weeks of treatment, serum creatinine decreased in LdT + ADV and ADV + LdT groups and eGFR increased (P < 0.05); Serum creatinine in ADV and ADV + LAM increased, and eGFR was decreased than before (P < 0.05). After treatment, there was no significant difference in renal function between the four groups at 24 weeks, but at week 52, eGFR increased and serum creatinine decreased in LdT + ADV group compared with LAM + ADV group (P < 0.05); ADV + LdT Compared with ADV + LAM group, eGFR increased and serum creatinine decreased (P < 0.05). At 52 weeks of treatment, 5 patients with mildly impaired renal function in the ADV + LdT group [n = 10, eGFR 60-90 ml·min(-1) ·(1.73 m(2))(-1)] returned to normal, and none of the ADV + LAM group (n = 9) returned to normal. Conclusion: For patients with mild impaired renal function, adding LdT combined with ADV can improve renal function compared to that of LAM plus ADV.

Motor development delay in offspring is associated with prenatal telbivudine exposure.

Telbivudine is an orally nucleoside analog with potent and specific antihepatitis B virus (HBV) activity, and it has been reported to block mother-to-infant transmission. However, few studies have focused on the safety of prenatal exposure for offspring development.This is a prospective noninterventional study. Participants were enrolled during delivery through the Women's Hospital of Zhejiang University School of Medicine between January 2012 and September 2013. Neonate's umbilical cord arterial blood (UCAB) was collected after delivery. Hepatitis B virus DNA copy, HBV serology, alanine aminotransferase (ALT), creatine kinase (CK), creatinine (CRE), and blood urea nitrogen (BUN) were measured. The development of the offspring was evaluated by the Chinese Revision of Bayley Scales of Child Development (BSCD-CR) at 12 to 24 months old.Around 30 and 31 chronic hepatitis B mothers were recruited in untreated group (non-LdT group) and telbivudine-treatment group (LdT group), respectively, and 2 children (one in non-LdT group and 1 in LdT group) were lost in follow-up. Sixty-one normal women and their children were recruited as a normal control (control group). Compared with non-LdT group, telbivudine treatment effectively blocks HBV transmission from mother to infant. However, CK in UCAB was significantly increased in the LdT group. Moreover, children with prenatal telbivudine exposure showed lower level of serum creatinine than non-LdT group, reduction of psychomotor developmental index and increased risk of motor development delay.Prenatal telbivudine exposure is correlated with motor development delay in offspring.

Real World Experience of Telbivudine Versus Entecavir in Patients with Chronic Hepatitis B, Including Long-Term Outcomes after Treatment Modification.

PurposeTo estimate long-term outcomes after treatment modification in patients with chronic hepatitis B (CHB) treated with entecavir (ETV) and telbivudine (LdT).Materials and MethodsThe study enrolled 131 nucleos(t)ide analogue (NA)-naïve CHB patients treated with ETV or LdT. During the 3-year study, NA treatment history including the incidence, the type of treatment modification, reasons for the modification, and overall complete virologic response (CVR) rate were retrospectively evaluated using the patients' medical records.ResultsAmong the 131 patients, 84 and 47 were initially treated with ETV and LdT, respectively. During the course of 3-year study, 82 patients in the ETV group (97.6%) maintained initial treatment whereas only 19 in the LdT group (40.4%). In the LdT group, 26 patients (92.9%) switched to another NA and another NA was added in 2 (7.1%) patients. An assessment of the CVR rate at 3 years, including treatment modification, showed that 89.3% and 95.7% of patients in the ETV and LdT groups, respectively, had undetectable serum hepatitis B virus DNA levels (p=0.329). Among LdT patients with treatment modification, the cumulative incidence rate of a CVR for rescue therapy was significantly higher in the tenofovir than in the ETV group (p=0.009).ConclusionDuring the 3-year study, there were no significant differences in the CVR between the ETV and LdT groups if appropriate rescue therapy was considered.

Diagnostic Accuracy of Basal Cortisol Level to Predict Adrenal Insufficiency in Cosyntropin Testing: Results from an Observational Cohort Study with 804 Patients

Adrenocorticotrophic hormone (ACTH) stimulation testing is the current standard for assessing primary and secondary adrenal insufficiency (AI). We aimed to investigate the value of basal cortisol level for prediction of AI. We retrospectively analyzed 804 consecutive patients who had high-dose (250 μg, HDT) or low-dose (1 μg, LDT) ACTH testing as part of their diagnostic work-up. Site-specific cut-off levels for AI were <550 in and <500 nmol/L in HDT and LDT, respectively. Overall, 70/400 (17.5%) in the LDT group and 118/404 (29.2%) in the HDT group showed an insufficient increase of cortisol and were categorized as AI. The receiver operating characteristic curve analysis showed an overall area under the curve (AUC) for basal cortisol of 0.88, which was comparable in LDT (area under the curve [AUC] 0.88) and HDT (AUC 0.88). If basal cortisol levels were ≥450 nmol/L (n = 234/804, 29.1%), the negative predictive value to rule out AI was 98.7%. If cortisol was ≤100 nmol/L (n = 69/804, 8.6%) the positive predictive value was 93.2% to rule in AI. There was a minimal additional value of the 30-minute cortisol level in HDT as compared to the 60-minute result, as well as for delta values. Basal cortisol levels ≤100 and ≥450 nmol/L were found in almost half of patients tested for possible AI and had high diagnostic accuracy, abolishing the need for formal ACTH testing. The 30-minute cortisol value in HDT did not increase diagnostic accuracy. These data may help guide clinicians when testing can safely be omitted, thereby reducing expenses and simplifying test protocols. ACTH = adrenocorticotropic hormone AI = adrenal insufficiency AUC = area under the curve CI = confidence interval HDT = high-dose test HPA axis = hypothalamus-pituitary-adrenal axis ITT = insulin tolerance test LDT = low-dose test NR = normal responders LR+/- = positive/negative likelihood ratio NPV = negative predictive value PPV = positive predictive value.

Comparison of Telbivudine and Entecavir therapy on estimates of glomerular filtration rate in patients with hepatitis B virus-related compensated cirrhosis

Objective To compare the impact of Telbivudine (LDT) and Entecavir (ETV) administration on estimates of glomerular filtration rate for anti-viral therapy in patients with hepatitis B virus (HBV)-related compensated cirrhosis by an open, prospective randomized controlled study. Methods Patients with HBV-related compensated cirrhosis at clinic or hospitalized in Shaoxing Municipal Hospital from January 2012 to June 2013 were included. A total of 170 patients were randomly divided into LDT (600 mg/d) or ETV (0.5 mg/d) groups at a ratio of 1∶1 according to the random number table method. All patients were treated for more than 36 months. The LDT group was optimized according to the roadmap.Patients with poor response or resistance in both treatment group were added with Adefovir dipivoxil (ADV) 10 mg/d for optimal treatment. The clinical outcome, creatinine (CR), estimated glomerular filtration rate (eGFR) of patients before and after 36 months of treatment were compared between two groups. All categorical data were analyzed using chi-square test and data accorded with normal distribution were compared by t test. Results After 36 months of treatment, the virological and biochemical responses in LDT group and ETV group were similar. The mean CR levels at month 24 and 36 in LDT group were (74.25±22.98) μmol/L and (70.72±24.75) μmol/L, respectively, which were both lower than baseline level ([83.09±17.68] μmol/L, t=2.811 and 3.145, respectively, both P<0.01). The mean CR levels at month 36 between two groups were statistically different (t=3.431, P=0.001). The mean eGFR levels at month 12, 24 and 36 in LDT group were all significantly lower than that at baseline (t=3.976, 8.297 and 10.629, respectively, all P<0.01). The mean eGFR levels at month 24 and 36 between two groups were statistically different (t=9.684 and 15.019, respectively, both P<0.01). A total of 64 patients including 34 in LDT group and 30 in ETV group had mild nephritic injury at baseline. The mean eGFR in patients with mild nephritic injury at baseline in LDT group at month 12, 24 and 36 were significantly different compared to baseline (t=6.098, 10.191 and 14.378, respectively, all P<0.01). The mean eGFR level at month 36 in ETV group had statistical difference compared to baseline (t=2.058, P<0.05). The mean eGFR levels at months 12, 24 and 36 were all statistical different between two groups (all P<0.01). The mean eGFR levels at month 24 and 36 in the optimized group were superior to ETV group (P<0.01). Conclusions In patients with HBV-related compensated cirrhosis, LDT and ETV treatment have similar clinical efficacy. LDT is more effective in protecting nephritic function than ETV. Key words: HBV related compensated cirrhosis; Estimates of glomerular filtration rate; Telbivudine; Entecavir