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  • 1
    Online Resource
    Online Resource
    Safety and effectiveness of metformin plus lifestyle intervention compared with lifestyle intervention alone in preventing progression to diabetes in a Chinese population with impaired glucose regulation: a multicentre, open-label, randomised controlled trial
    Elsevier BV ; 2023
    In:  The Lancet Diabetes & Endocrinology Vol. 11, No. 8 ( 2023-08), p. 567-577
    Details
    In: The Lancet Diabetes & Endocrinology, Elsevier BV, Vol. 11, No. 8 ( 2023-08), p. 567-577
    Type of Medium: Online Resource
    ISSN: 2213-8587
    URL: Article
    DOI: 10.1016/S2213-8587(23)00132-8
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    Long-Term Ozone Exposure and Small Airway Dysfunction: The China Pulmonary Health (CPH) Study
    American Thoracic Society ; 2022
    In:  American Journal of Respiratory and Critical Care Medicine Vol. 205, No. 4 ( 2022-02-15), p. 450-458
    Details
    In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 205, No. 4 ( 2022-02-15), p. 450-458
    Type of Medium: Online Resource
    ISSN: 1073-449X , 1535-4970
    URL: Article
    DOI: 10.1164/rccm.202107-1599OC
    RVK:
    XA 21200
    Language: English
    Publisher: American Thoracic Society
    Publication Date: 2022
    detail.hit.zdb_id: 1468352-0
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  • 3
    Online Resource
    Online Resource
    Sustained viral response and relapse after discontinuation of oral antiviral drugs in HBeAg-positive patients with chronic hepatitis B infection
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-25)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-25)
    Abstract: To investigate the sustained virological response and relapse in chronic hepatitis B (CHB) patients with hepatitis B e antigen (HBeAg) positive after stopping oral antiviral drugs, and to monitor the disease progression and the incidence of adverse events such as liver cirrhosis and hepatocellular carcinoma. Methods This is a prospective observational study. Patients who continued nucleos(t)ide analogue (NA) treatment after achieving HBeAg seroconversion for more than 3 years were enrolled. After signing the informed consent form, patients stopped NA treatment and received follow-up. During the follow-up, the antiviral treatment information of the patients was collected, and the follow-up observation was carried out every 3 months since the enrollment. We monitored the virological indexes, liver and kidney function, serology and liver imaging during follow-up. The purpose of this study was to explore the sustained virological response rate, HBV DNA recurrence rate, clinical relapse rate and the related factors after drug withdrawal. Results A total of 82 patients were enrolled, including 42 males (51.22%) and 40 females (48.78%), with a median age of 34.00 (31.00, 37.25) years. All enrolled patients were followed up for 1 year. At the end of the follow-up, 36.59% (30/82) of patients had sustained virological response, 63.41% (52/82) of patients had HBV DNA reactivation, 17.07% (14/82) of patients had clinical relapse, and 10.98% (9/82) of patients had HBeAg reversion. During the follow-up, there were no adverse events such as liver cirrhosis and hepatocellular carcinoma. The median level of hepatitis B surface antigen (HBsAg) in patients with sustained virological response was lower than that in patients with HBV DNA reactivation (2.92 vs.3.18 log 10 IU/ml, Z =-1.492/ P =0.136), and the median level of baseline HBsAg in patients with HBV DNA reactivation was lower than that in patients with clinical relapse (3.01 vs.3.45 log 10 IU/mL, Z =-1.795/ P =0.073), but the difference was not significant. There was no significant statistical difference between patients with sustained virological response and HBV DNA reactivation of the median total treatment time [69.50 (56.25, 86.00) vs.62.50 (44.00, 88.50) months, Z =-0.689/ P =0.491], and the consolidation treatment time [41.50 (36.75, 54.75) vs.40.50 (36.00, 53.75) months, Z =-0.419/ P =0.675]. Conclusion The sustained virological response rate of HBeAg positive CHB patients after stopping oral antiviral treatment is lower, and it is more common in patients with lower HBsAg levels. Patients still need to be closely monitored after stopping NA therapy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1082091
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 4
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    Online Resource
    Effects of hepatitis B virus infection and strategies for preventing mother-to-child transmission on maternal and fetal T-cell immunity
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 14 ( 2023-2-16)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 14 ( 2023-2-16)
    Abstract: One of the most common routes of chronic hepatitis B virus (HBV) infection is mother-to-child transmission (MTCT). Approximately 6.4 million children under the age of five have chronic HBV infections worldwide. HBV DNA high level, HBeAg positivity, placental barrier failure, and immaturity of the fetal immune are the possible causes of chronic HBV infection. The passive-active immune program for children, which consists of the hepatitis B vaccine and hepatitis B immunoglobulin, and antiviral therapy for pregnant women who have a high HBV DNA load (greater than 2 × 10 5 IU/ml), are currently two of the most important ways to prevent the transmission of HBV from mother to child. Unfortunately, some infants still have chronic HBV infections. Some studies have also found that some supplementation during pregnancy can increase cytokine levels and then affect the level of HBsAb in infants. For example, IL-4 can mediate the beneficial effect on infants’ HBsAb levels when maternal folic acid supplementation. In addition, new research has indicated that HBV infection in the mother may also be linked to unfavorable outcomes such as gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and premature rupture of membranes. The changes in the immune environment during pregnancy and the hepatotropic nature of HBV may be the main reasons for the adverse maternal outcomes. It is interesting to note that after delivery, the women who had a chronic HBV infection may spontaneously achieve HBeAg seroconversion and HBsAg seroclearance. The maternal and fetal T-cell immunity in HBV infection is important because adaptive immune responses, especially virus-specific CD8 T-cell responses, are largely responsible for viral clearance and disease pathogenesis during HBV infection. Meanwhile, HBV humoral and T-cell responses are important for the durability of protection after fetal vaccination. This article reviews the literature on immunological characteristics of chronic HBV-infected patients during pregnancy and postpartum, blocking mother-to-child transmissions and related immune mechanisms, hoping to provide new insights for the prevention of HBV MTCT and antiviral intervention during pregnancy and postpartum.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2023.1122048
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 5
    Online Resource
    Online Resource
    Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 13 ( 2023-1-4)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-4)
    Abstract: In order to develop immune tolerant to the fetal, maternal immune system will have some modification comparing to the time before pregnancy. Immune tolerance starts and develops at the maternal placental interface. In innate immunity, decidual natural killer (dNK) cells, macrophages and dendritic cells play a key role in immue tolerance. In adaptive immunity, a moderate increase of number and immune inhibition function of regulatory T cells (Treg) are essential for immune tolerance. The trophoblast cells and immune cells expressing indoleamine 2,3-dioxygenase (IDO), the trophoblast cells expressing HLA-G, and Th1/Th2 shifting to Th2 dominant and Th17/Treg shifting to Treg domiant are in favor of maternal fetal immune tolerance. Steroids (estrogen and progesterone) and human chorionic gonadotropin (HCG) also participate in immune tolerance by inducing Treg cells or upregulating immunosuppressive cytokines. Most of the patients with chronic HBV infection are in the “HBV immune tolerance period” before pregnancy, and the liver disease is relatively stable during pregnancy. In chronic HBV infection women, after delivery, the relative immunosuppression in vivo is reversed, and Th1 is dominant in Th1/Th2 and Th17 is dominant in Th17/Treg balance. After delivery, the number of Treg decrease and NK cells increase in quantity and cytotoxicity in peripheral blood. Liver NK cells may cause liver inflammation through a non-antigen specific mechanism. After delivery, the number of CD8 + T cells will increase and HBV specific T cell response recovers from the disfunction in pregnancy. Under the background of postpartum inflammation, the rapid decrease of cortisol after delivery, and especially the enhancement of HBV specific T cell response induced by HBV DNA and cytokines, are the main reasons for postpartum hepatitis. HBeAg positive, especially HBeAg & lt;700 S/CO, and HBV DNA & gt;3-5Log 10 IU/ml are risk factors for postpartum hepatitis. Antiviral treatment in late pregnancy can reduce the incidence of mother to child transmission (MTCT) in chronic HBV infection women. Chronic HBV infection women have hepatitis both during pregnancy and more often in 12 weeks postpartum. It is generally agreed that postpartum hepatitis is mild symptoms and self-limited. Delaying drug withdrawal to 48 weeks can increase the seroconversion rate of HBeAg in delivery women with elevated alanine aminotransferase (ALT) in pregnancy.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1112234
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 6
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    Online Resource
    Impact of in vitro fertilization‐embryo transfer on mother‐to‐infant transmission in women with chronic HBV infection
    Wiley ; 2022
    In:  Liver International Vol. 42, No. 10 ( 2022-10), p. 2167-2174
    Details
    In: Liver International, Wiley, Vol. 42, No. 10 ( 2022-10), p. 2167-2174
    Abstract: In vitro fertilization‐embryo transfer (IVF‐ET) may increase the risk of mother‐to‐child transmission (MTCT) of hepatitis B virus (HBV). The purpose of this study was to investigate the impact and safety of IVF‐ET on MTCT in women with chronic HBV infection (CHB). Methods The data of 298 women who got pregnant by IVF‐ET and their 375 children were collected retrospectively. Mothers were divided into the CHB group ( n  = 224) and the control group (HBsAg negative, n  = 74). After birth, newborns were routinely vaccinated with the hepatitis B vaccine, and infants in the CHB group were injected with hepatitis B immunoglobulin within 2 h after birth. Demographic information, clinical data and laboratory test results were collected. The primary outcome measures were the MTCT rate of HBV, and the secondary outcome measures were the safety of the mother and infant. Results There was no case of HBV MTCT in all 282 newborns born in the CHB group and 93 neonates born in the control group. Of the two groups, the birth weight (3056.74 ± 601.65 vs. 2926.24 ± 704.86, P  = .083), length (49.22 ± 1.97 vs. 48.74 ± 3.09, P  = .167), 5‐min Apgar score (9.97 ± 0.21 vs. 9.90 ± 0.51, P  = .212), days of pregnancy (265.70 ± 12.73 vs. 262.02 ± 17.50, P  = .064) and neonatal malformation rate (0.71% vs. 0, P  = 1.000) were similar. Two cases of neonatal malformation occurred in the CHB group. The incidences of pregnancy and childbirth complications were similar between the two groups. Conclusion IVF‐ET does not increase the risk of MTCT in women with chronic HBV infection, and it is safe for mothers and infants.
    Type of Medium: Online Resource
    ISSN: 1478-3223 , 1478-3231
    URL: Issue
    URL: Article
    DOI: 10.1111/liv.v42.10
    DOI: 10.1111/liv.15349
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2124684-1
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  • 7
    Online Resource
    Online Resource
    Image_1.tif
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-21)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-21)
    Abstract: To explore whether the frequencies and functional molecules expression of Natural Killer cells (NK cells) are related to hepatitis B surface antigen (HBsAg) disappearance in hepatitis B e envelope antigen (HBeAg)-positive patients with chronic hepatitis B (CHB) throughout peginterferon alpha-2a (PEG-IFN α-2a) treatment. Methods In this prospective research, HBeAg-positive patients with CHB received PEG-IFN α-2a treatment, completing 4-year follow-up. After PEG-IFN α-2a treatment, undetectable HBV DNA, HBsAg loss, and HBeAg disappearance were defined as functional cure. Proportions of NK, CD56 dim , CD56 bright , NKp46 + , NKp46 dim , NKp46 high , and interferon alpha receptor 2 (IFNAR2) + NK cells, and the mean fluorescence intensity (MFI) of NK cell surface receptors IFNAR2 and NKp46 were detected. Results 66 patients were enrolled into the study in which 17 patients obtained functional cure. At baseline, hepatitis B virus desoxyribose nucleic acid (HBV DNA) titer in patients with functional cure was remarkably lower than that in Non-functional cure group. Compared with baseline, HBV DNA levels, HBsAg levels, and HBeAg levels significantly declined at week 12 and 24 of therapy in patients with functional cure. At baseline, the negative correlation between CD56 bright NK% and HBV DNA and the negative correlation between CD56 dim NK% and HBV DNA was showed; CD56 bright NK% and IFNAR2 MFI in patients with functional cure were remarkably higher than those in patients without functional cure. After therapy, CD56 bright NK% and NKp46 high NK% in patients with functional cure were higher than those in patients without functional cure. In Functional cure group, after 24 weeks of treatment NK%, CD56 bright NK%, IFNAR2 MFI weakly increased, and NKp46 high NK% and NKp46 MFI significantly increased, meanwhile, CD56 dim NK% and NKp46 dim NK% decreased. Only NKp46 MFI increased after therapy in patients without functional cure. Conclusion The lower HBV DNA load and the higher CD56 bright NK% before therapy, and the higher the post-treatment CD56 bright NK%, IFNAR2 MFI, NKp46 high NK%, the easier to achieve functional cure.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    URL: Article
    DOI: 10.3389/fimmu.2022.1067362
    DOI: 10.3389/fimmu.2022.1067362.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 8
    Online Resource
    Online Resource
    Study on liver histopathology of chronic HBV infected patients with different normal ALT values
    Frontiers Media SA ; 2022
    In:  Frontiers in Immunology Vol. 13 ( 2022-11-22)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2022-11-22)
    Abstract: Comparison of liver histopathological findings to explore the occurrence of liver inflammation in patients with chronic hepatitis B (CHB) under different alanine aminotransferase (ALT) normal values. Methods The patients who were diagnosed as chronic hepatitis B virus (HBV) infection by liver histopathology at the Department of Pathology, Beijing Ditan Hospital due to clinical difficulty in defining the degree of liver inflammation or fibrosis were retrospectively enrolled from May 2008 to November 2020. Study of the incidence of significant hepatic histopathology in enrolled patients according to different ALT normal values. Using logistic regression to investigate the relevant factors of significant hepatic histopathology. Results A total of 1474 patients were enrolled, 56.20% of the patients were male, and the overall patients’ age was 36.80 ± 10.60 years. 39.00% of patients had liver inflammation grade G & gt; 1, 34.70% liver fibrosis stage S & gt; 1, and 48.17% patients had significant hepatic histopathology (G & gt; 1 and/or S & gt; 1). Among patients with normal ALT values, 36.40% and 40.40% had significant hepatic histopathology by American Association for the Study of Liver Diseases (AASLD) criteria and Chinese guideline criteria, respectively, but the difference was not statistically significant ( χ 2 = 3.38, P =0.066). In contrast, among patients with abnormal ALT values, 58.90% and 62.20% of patients had significant hepatic histopathology by AASLD criteria and Chinese guideline criteria, respectively, with no significant difference ( χ 2 = 2.28, P =0.131). ALT ( P & lt; 0.001, OR=1.019), hepatitis B surface antigen (HBsAg) ( P & lt; 0.001, OR=0.665) and hepatitis B e antigen (HBeAg) status ( P & lt; 0.001, OR=2.238) were relevant factors in the occurrence of significant hepatic histopathology. ALT was positively corelated with grade of inflammation G (r =0.194, P & lt; 0.001) and negatively correlated with liver fibrosis stage S (r =-0.066, P =0.021). Conclusions Our study found no statistically significant differences in the presence of significant hepatic histopathology under the two ALT criteria. ALT, HBsAg and HBeAg status were related to the occurrence of significant hepatic histopathology.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1069752
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2606827-8
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  • 9
    Online Resource
    Online Resource
    Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 13 ( 2023-1-5)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-5)
    Abstract: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. Methods We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. Results 85 HBV DNA-negative and HBeAg-negative patients were 37.90 ± 10.30 years old, 23.50% of patients with grade of inflammation (G) & gt;1, 35.30% of patients with liver fibrosis stage (S) & gt;1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 ± 10.70 vs 34.80 ± 8.87 years, t=-3.28, P =0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) μmol/L, z=-2.26, P =0.024], lower cholinesterase (CHE) (t=-2.86, P =0.005, 7388.00 ± 2156.00 vs 8988.00 ± 2823.00 U/L) and lower platelet (PLT) (t=2.75, P =0.007, 157.00 ± 61.40 vs 194.00 ± 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P =0.020, 66.70% vs 337.50%). G had significant correlation with CHE ( P =0.008, r=-0.23), alanine aminotransferase (ALT) ( P =0.041, r=0.18), aspartate aminotransferase (AST) ( P =0.001, r=0.29). S had significant correlation with TBIL ( P = 0.008, r = 0.23), age ( P & lt; 0.001, r = 0.32), international normalized ratio (INR) ( P = 0.04, r = 0.23), CHE ( P & lt; 0.001, r = -0.30), PLT ( P & lt; 0.001, r = -0.40) and prothrombin time activity (PTA) ( P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P =0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. Conclusions A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1113070
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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  • 10
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    Online Resource
    Dynamic changes of the proportion of HLA-DR and CD38 coexpression subsets on T lymphocytes during IFN-based chronic hepatitis B treatment
    Frontiers Media SA ; 2023
    In:  Frontiers in Immunology Vol. 13 ( 2023-1-24)
    Details
    In: Frontiers in Immunology, Frontiers Media SA, Vol. 13 ( 2023-1-24)
    Abstract: To investigate the changes of human leukocyte antigen DR (HLA-DR) and CD38 coexpression subsets on T lymphocytes following interferon (IFN) therapy for those who have chronic hepatitis B (CHB). Methods A prospective cohort of CHB patients participated in this study. CHB patients without IFN treatment (including naïve and nucleoside [nucleotide] analogs [NAs] -treated patients) were given pegylated interferon alfa (Peg-IFNα) treatment. Peripheral blood samples were taken at baseline, 4 weeks and 12-24 weeks of Peg-IFNα treatment. For the patients who entered the Peg-IFNα plateau phase due to the stagnation of the decrease in HBsAg, and Peg-IFNα was discontinued and Peg-IFNα therapy was resumed after an interval of 12-24 weeks. During the interval, they received first-line NAs treatment. Peripheral blood samples were collected at the baseline of the plateau phase, 12-24 weeks of intermittent treatment, and 12-24 weeks of Peg-IFNα retreatment. The peripheral blood samples were taken to determine virological, serological and biochemical indices of hepatitis B virus (HBV), and T lymphocyte related phenotypes were detected using flow cytometry. Results In the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR + CD38 dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR + CD38 hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR + CD38 hi subset percentage. The persistent high proportion of HLA-DR + CD38 hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR + CD38 hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR + CD38 hi subsets significantly increased, but it was still lower than that at the baseline level. Conclusions The spectrum of HLA-DR and CD38 coexpression subsets on T lymphocytes changed during the long-term treatment of IFN. The establishment of the IFN plateau phase was linked to the persistence of a considerable proportion of HLA-DR + CD38 hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR + CD38 hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.
    Type of Medium: Online Resource
    ISSN: 1664-3224
    URL: Article
    DOI: 10.3389/fimmu.2022.1116160
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2606827-8
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