Search

ObjectiveTo explore any correlation between serum urate (SU) level or insulin resistance (IR) and metabolic dysfunction associated steatotic liver disease (MASLD) in patients with metabolic syndrome (MS).MethodsData from all MASLD patients, diagnosed by liver biopsy, were enrolled and divided into MASLD alone group and MASLD with MS group. They were subdivided into hyperuricemia group and normal SU group to find correlation between SU/IR and MASLD in patients with MS and independent risk factors for MASLD.ResultsData from 539 MASLD patients were analyzed. Body mass index (BMI) (p = 0.000), waist circumference (WC) (p = 0.004), and low-density lipoprotein (LDL) (p = 0.000) were dramatically higher in MASLD with MS group than those with MASLD alone; MASLD with MS patients had significantly more family history of diabetes (p = 0.000) and hypertension (p = 0.000) than patients with MASLD alone. Height (p = 0.000), weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.001), and LDL (p = 0.007) were dramatically higher in hyperuricemia patients than those with normal SU. SU was inversely associated with age (p = 0.000) and high-density lipoprotein (HDL) (p = 0.003), and positively correlated with weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.000), TG (p = 0.000), and LDL (p = 0.000). Logistic Regression analysis showed that age (p = 0.031), TG (p = 0.002), LDL (p = 0.010), HbA1c (p = 0.026), and family history of hypertension (p = 0.000) may be independent risk factors for MASLD in patient with MS.ConclusionInsulin resistance (IR) in MASLD patients with MS, but not higher SU levels, has closer correlation with the occurrence of MASLD in patients with family history of hypertension and diabetes having higher BMI, LDL, HbA1c.

To explore the impact of ursodeoxycholic acid (UDCA) on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and clinical outcomes in patients with autoimmune liver disease (AILD). Patients diagnosed with AILD were enrolled and divided into a UDCA group and a non-UDCA group based on whether they received UDCA treatment. Relevant data were collected regarding AILD diagnosis, treatment, biochemical indicators, and imaging examination. The incidence of SARS-CoV-2 infection and the prognosis of AILD patients were observed. A total of 1,138 patients completed follow-up. The usage rate of hormone (P = 0.003) and immunosuppressant (P = 0.001) used for treating AILD in the non-UDCA group was markedly lower than in the UDCA group. The UDCA usage rate was markedly lower in SARS-CoV-2 infected patients than in uninfected patients (P = 0.003). The rate of SARS-CoV-2 infection in the non-UDCA group was significantly higher than in the UDCA group (P = 0.018). Logistic regression analysis showed that UDCA use (P = 0.003) was correlated to a lower incidence of SARS-CoV-2, while immunosuppressant use (P = 0.017) increased the incidence. Recovery time from SARS-CoV-2 infection was markedly longer for those receiving UDCA treatment than those in the non-UDCA group (P = 0.018). UDCA is associated with low SARS-CoV-2 incidence in AILD patients, while immunosuppressant increases its incidence instead. Patients receiving UDCA treatment have a longer recovery time after being infected.

ABSTRACTBackground Studies have shown acute flares of chronic hepatitis B (CHB) might be related to immunologic changes that occur during pregnancy. However, the indicators for predicting acute flares of CHB among pregnant women still need further study. We aimed to distinguish the relevance between serum levels of HBcrAg and acute flares of CHB in pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy.Methods A total of 172 chronic HBV-infected pregnant women who were judged to be in the immune-tolerant phase were recruited in our research. All patients received short-course antiviral therapy with TDF. The biochemical, serological, and virological parameters were measured using standard laboratory procedures. The serum levels of HBcrAg were tested by ELISA.Results Fifty-two (30.2%) out of 172 patients had acute flares of CHB. At postpartum week 12 (TDF cessation), serum HBcrAg (OR, 4.52; 95% CI, 2.58–7.92) and HBsAg (OR, 2.52; 95% CI, 1.13–5.65) were associated with acute flares of CHB. The serum HBcrAg levels were beneficial for confirmation of patients with acute flares of CHB, with an area under the ROC curve of 0.84 (95% CI, 0.78–0.91).Conclusions For pregnant women with chronic HBV infection in the immune-tolerant phase, serum HBcrAg and HBsAg levels at postpartum week 12 were associated with acute flares of CHB after short-course antiviral therapy with TDF. The serum HBcrAg level can correctly identify acute flares of CHB and may be a predictor of the need for continuing antiviral therapy after 12 weeks postpartum.

ABSTRACTThe purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688–0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT.

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 × 105 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.

BackgroundTo investigate the changes of natural killer (NK) cell phenotype in the interferon alpha (IFN-α) treatment of chronic hepatitis B (CHB) and its relationship with clinical indicators.MethodsThe CHB patients who did not receive any antiviral treatment were set as initial treatment group and used pegylated interferon alpha (PEG-IFN α). Peripheral blood samples were collected at baseline, 4 weeks, and 12-24 weeks. For IFN-treated patients who entered the plateau were set as plateau group, and PEG-IFN α was discontinued and resumed after an interval of 12-24 weeks. Besides, we also enrolled some patients who had received oral drug for more than 6 months as oral drug group without follow up. Peripheral blood was collected during the plateau period, which was set as baseline, and after 12-24 weeks of intermittent treatment, and after 12-24 weeks of additional treatment with PEG-IFN α. The aim of the collection was to detect hepatitis B virus (HBV) virology, serology and biochemical indicators, and the NK cell related phenotype was detected by flow cytometry.ResultsIn the plateau group, subgroup of CD69+CD56dim was higher with statistical significance when comparing with the initial treatment group and oral drug group [10.49 (5.27, 19.07) vs 5.03 (3.67, 8.58), Z = -3.11, P = 0.002; 10.49 (5.27, 19.07) vs 4.04 (1.90, 7.26), Z = -5.30, P < 0.001)]. CD57+CD56dim was significantly lower than that in initial treatment group and oral drug group respectively [68.42±10.37 vs 55.85±12.87, t = 5.84, P < 0.001; 76.38±9.49 vs 55.85±12.87, t = -9.65, P < 0.001]. The CD56brightCD16- subgroup in the plateau group was higher with statistical significance compared with initial treatment group and oral drug group respectively [11.64 (6.05, 19.61) vs 3.58 (1.94, 5.60), Z = -6.35, P < 0.001; 11.64 (6.05, 19.61) vs 2.37 (1.70, 4.30), Z = -7.74, P < 0.001)]. CD57+CD56dim in the plateau group had a significant higher percentage than that at baseline after IFN discontinuation for 12-24 weeks (55.85±12.87 vs 65.95±12.94, t = -2.78, P = 0.011).ConclusionDuring the long-term treatment of IFN, the killer subgroup of NK cells is continuously depleted, leading to the differentiation of the regulatory subgroup into the killer subgroup. In the killing subgroup, although the number is continuously depleted, the activity of the subgroup is continuously increased. In the plateau phase, after stopping IFN for a period of time, the number of NK cell subsets would gradually recover, but was still lower than that in the initial treatment group.

BackgroundTo 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).MethodsA 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.ResultsIn the process of long-term treatment of Peg-IFNα, the percentage of HLA-DR+CD38dim subsets increased significantly at first, then decreased gradually, while the percentage of HLA-DR+CD38hi subsets markedly increased. During long-term Peg-IFNα treatment, there was a considerable negative correlation between HBsAg and the HLA-DR+CD38hi subset percentage. The persistent high proportion of HLA-DR+CD38hi subsets was related to the occurrence of Peg-IFNα plateau phase. After Peg-IFNα intermittent treatment, the percentage of HLA-DR+CD38hi subsets decreased significantly. After Peg-IFNα retreatment, the level of HBsAg began to decrease again. At the same time, the percentage of HLA-DR+CD38hi subsets significantly increased, but it was still lower than that at the baseline level.ConclusionsThe 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+CD38hi subsets on T lymphocytes. IFN intermittent treatment could significantly reduce the proportion of HLA-DR+CD38hi subsets, helping regain the antiviral efficacy of IFN during IFN retreatment.

ObjectivePrecise assessment of liver inflammation in untreated hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B virus (HBV) infection can determine when to initiate antiviral therapy. The aim of this study was to develop and validate a nomogram model for the prediction of non-minimal liver inflammation based on liver pathological injuries combined with age and alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B surface antigen (HBsAg), HBeAg, and HBV DNA quantification.MethodsWe retrospectively included 735 HBeAg-positive chronic hepatitis B (CHB) patients with ALT

AimsStudy 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.MethodsWe 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.Results85 HBV DNA-negative and HBeAg-negative patients were 37.90 ± 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >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 < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 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.ConclusionsA 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

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 HBeAg3-5Log10IU/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.

ObjectiveTo 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.MethodsThis 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.ResultsA 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 log10IU/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 log10IU/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].ConclusionThe 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.

AimsComparison 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.MethodsThe 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.ResultsA 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 > 1, 34.70% liver fibrosis stage S > 1, and 48.17% patients had significant hepatic histopathology (G > 1 and/or S > 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 (χ2 =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 (χ2 =2.28, P =0.131). ALT (P

ObjectiveTo 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.MethodsIn 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, CD56dim, CD56bright, NKp46+, NKp46dim, NKp46high, and interferon alpha receptor 2 (IFNAR2)+ NK cells, and the mean fluorescence intensity (MFI) of NK cell surface receptors IFNAR2 and NKp46 were detected.Results66 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 CD56bright NK% and HBV DNA and the negative correlation between CD56dim NK% and HBV DNA was showed; CD56bright NK% and IFNAR2 MFI in patients with functional cure were remarkably higher than those in patients without functional cure. After therapy, CD56bright NK% and NKp46high 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%, CD56bright NK%, IFNAR2 MFI weakly increased, and NKp46high NK% and NKp46 MFI significantly increased, meanwhile, CD56dim NK% and NKp46dim NK% decreased. Only NKp46 MFI increased after therapy in patients without functional cure.ConclusionThe lower HBV DNA load and the higher CD56bright NK% before therapy, and the higher the post-treatment CD56bright NK%, IFNAR2 MFI, NKp46high NK%, the easier to achieve functional cure.

ObjectiveTo explore the correlation between postpartum hepatitis and changes of plasmacytoid dendritic cells’ (pDC) function and frequency in hepatitis B e antigen (HBeAg)-positive pregnant women with chronic hepatitis B virus (HBV) infection.MethodsPregnant women with chronic HBV infection receiving antiviral treatment (treated group) or not receiving antiviral treatment (untreated group) were enrolled and demographic information was collected before delivery. Clinical biochemical, virological serology, pDC frequency and functional molecular expression were tested before delivery and at 6, 12, 24 weeks after delivery.Results90 eligible pregnant women were enrolled, 36 in the untreated group and 54 in the treated group. 36 patients developed postpartum hepatitis, including 17 (17/36, 47.2%) in the untreated group and 19 (19/54, 35.2%) in the treated group (χ2 = 1.304 p=0.253), and 22 cases of hepatitis occurred at 6 weeks postpartum, 12 at 12 weeks postpartum, and 2 at 24 weeks postpartum. The alanine transaminase (ALT) levels at any time postpartum were significantly higher than that of the antepartum, especially at 6 weeks and 12 weeks postpartum. However, the frequencies of pDCs, CD83+ pDCs and CD86+ pDCs antepartum had no significant difference from any time postpartum. The frequencies of CD83+ pDCs, CD86+ pDCs in the treated group antepartum were significantly higher than those in the untreated group [12.70 (9.46, 15.08) vs. 10.20 (7.96, 11.85), p=0.007; 22.05 (19.28, 33.03) vs. 18.05 (14.33, 22.95), p=0.011], and the same at 12 weeks postpartum [12.80 (10.50, 15.50) vs. 9.38 (7.73, 12.60), p=0.017; 22.50 (16.80, 31.20) vs. 16.50 (12.65, 20.80), p=0.001]. The frequency of CD86+ pDCs in the treated group was significantly higher than that in the untreated group at 24 weeks postpartum [22.10 (16.70, 30.00) vs. 17.10 (13.70, 20.05), p=0.006].ConclusionsPostpartum hepatitis in HBV infected women mainly occurs at 6-12 weeks postpartum. Antiviral treatment during pregnancy can significantly increase the frequencies of CD83+ pDCs and CD86+ pDCs in pregnant women with chronic HBV infection.

ObjectiveWe explore the expression of functional molecules on CD8+ T lymphocytes, cytokines concentration, and their correlation to occurrence of hepatitis B and hepatitis B virus (HBV) desoxyribose nucleic acid (DNA), hepatitis B surface antigen (HBsAg), hepatitis B envelope antigen (HBeAg), and alanine aminotransferase (ALT) in patients infected with HBV.MethodsThis is a single center study. 32 patients with acute hepatitis B (AHB), 30 patients with immune tolerant (IT) phase chronic HBV infected, and 50 patients with chronic hepatitis B (CHB) were enrolled. The activation molecules (CD69) and the apoptosis-inducing molecules (CD178) on surface of CD8+ T lymphocytes were tested by the flow cytometry. Fms-like tyrosine kinase 3 ligand (Flt-3L), interleukin 17A (IL-17A), interferon γ (IFN-γ), and Interferon α2 (IFN-α2) were quantitated by Luminex assay. We use linear regression analysis to analyze their correlations to ALT, HBV DNA, HBsAg, and HBeAg.ResultsThe frequency of CD69+CD8+ T lymphocytes in CHB and AHB groups were increased significantly compared with IT group (4.19[3.01, 6.18]% and 4.45[2.93, 6.71]% vs. 3.02[2.17, 3.44]%; H=26.207, P=0.001; H=28.585, P=0.002), and the mean fluorescence intensity (MFI) of CD69 in AHB group was significantly higher than IT and CHB groups (27.35[24.88, 32.25] vs. 20.45[19.05, 27.75] and 23.40[16.78, 28.13]; H=25.832, P=0.005 and H=22.056, P=0.008). In IT group, HBsAg levels and HBV DNA loads were negatively correlated with CD69MFI (β=-0.025, t=-2.613, P=0.014; β=-0.021, t=-2.286, P=0.030), meanwhile, HBeAg was negatively related to the frequency of CD69+CD8+ T lymphocytes (β=-61.306, t=-2.116, P=0.043). In AHB group, IFN-α2 was positively related to the frequency of CD8+ T lymphocytes (β=6.798, t=2.629, P=0.016); however, in CHB group, IFN-α2 was negatively associated with frequency of CD8+ T lymphocytes (β=-14.534, t=-2.085, P=0.043). In CHB group, HBeAg was positively associated with frequency of CD69+CD8+ T lymphocytes (β=43.912, t=2.027, P=0.048). In AHB group, ALT was positively related to CD69MFI (β=35.042, t=2.896, P=0.007), but HBsAg was negatively related to CD178MFI (β=-0.137, t=-3.273, P=0.003).ConclusionsThe activation of CD8+ T lymphocytes was associated with the occurrence of AHB and CHB. However, due to the insufficient expression of functional molecules of CD8+ T lymphocytes and the depletion of CD8+ T lymphocytes, CHB patients were difficult to recover from HBV infection.

ObjectiveTo study the effect of antiviral therapy during pregnancy on the frequency of natural killer (NK) cells in peripheral blood of women with HBV DNA positive chronic hepatitis B (CHB).MethodIn total 124 female subjects were divided into four groups: 11 healthy non-pregnant women (Normal group), 26 non-pregnant women in immune tolerance period of chronic hepatitis B virus (HBV) infection (CHB group), 41 pregnant CHB women without antiviral treatment during pregnancy (Untreated group), and 46 pregnant CHB women receiving antiviral treatment during pregnancy (Treated group). The frequency of NK cells in peripheral blood were detected by flow cytometry.ResultThe frequency of NK cells in healthy women [15.30 (12.80, 18.40)] was higher than that in women with HBV infection, but there was no significant statistical difference (p=0.436). The frequency of NK cells in CHB group [10.60 (6.00, 18.30)] was higher than those in pregnant CHB women [Untreated: 6.90 (4.89, 10.04), P=0.001; Treated: 9.42 (6.55, 14.10), P=0.047]. The frequency of NK cells in treated group was significantly higher than that in untreated group (P = 0.019). The frequencies of NK cells, CD56bright NK cells and NKp46dim NK cells at 12 and 24 weeks postpartum in the untreated group were increased significantly than those before delivery. In treated group, the frequencies of NK cells, CD56bright NK cells, NKp46+ NK cells and NKp46dim NK cells were significantly increased at 6 and 12 weeks than those before delivery. The frequencies of NK cells and CD56bright NK cells postpartum were increased significantly in treated group than those in untreated group. The frequencies of CD56dim NK cells decreased significantly after delivery in treated than those in untreated patients. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) significantly increased after delivery than those before delivery. The results showed that the postpartum ALT level was weak positive correlated with NKp46high frequency (r=0.199) and was weak negative correlated with NKp46dim frequency (r= -0.199).ConclusionAntiviral treatment during pregnancy could significantly increase the frequency of NK cells postpartum. Postpartum hepatitis may be related to the immune injury caused by change of NK cell frequency and HBV infection.

Abstract Background Antiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy. Methods Thirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+ T cells, CD4+ T cells, CD68+ mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence. Results The overall median frequency of CD8+ T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p

Metagenomics is a new approach to study microorganisms obtained from a specific environment by functional gene screening or sequencing analysis. Metagenomics studies focus on microbial diversity, community constitute, genetic and evolutionary relationships, functional activities, and interactions and relationships with the environment. Sequencing technologies have evolved from shotgun sequencing to high-throughput, next-generation sequencing (NGS), and third-generation sequencing (TGS). NGS and TGS have shown the advantage of rapid detection of pathogenic microorganisms. With the help of new algorithms, we can better perform the taxonomic profiling and gene prediction of microbial species. Functional metagenomics is helpful to screen new bioactive substances and new functional genes from microorganisms and microbial metabolites. In this article, basic steps, classification, and applications of metagenomics are reviewed.