Hepatitis B chronic infection among pregnant women attending the antenatal care in Bor State Referral Hospital, South Sudan

Introduction: Hepatitis B virus (HBV) is a major public health problem affecting 400 million people worldwide, and is a common cause of chronic liver failure (cirrhosis) and hepatocellular carcinoma. Sixty-eight percent of infected people are from the African and Pacific regions. Vertical transmission from mother to newborn baby is one of the mechanisms by which chronic hepatitis virus infection spreads, besides infections from contaminated needles and syringes and sexual contact. Hepatitis B chronic infection is endemic in many poor countries, especially in Africa. Method: A cross-sectional study was conducted between July and August 2021. Pregnant women attending the antenatal care (ANC) in Bor State referral hospital, South Sudan, were interviewed to collect information on their socio-demographic characteristics and risk factors for hepatitis B infection. The objective was to determine the seroprevalence of hepatitis B chronic infection through blood testing. Prevalence ratios for certain risk factors were calculated. Results: Two hundred pregnant women were enrolled. The Prevalence Rate for chronic infection with hepatitis B virus, diagnosed using the rapid immune-chromatographic assay for Hepatitis B surface antigen (HBsAg), was 8.5%. (95% CI; 4.7% - 12.3%). None of the suspected risk factors studied were found to be significantly associated with testing positive for HBV, except for a history of previous jaundice. Conclusion: The prevalence of HBV chronic infection among pregnant women in Bor, Jonglei State, is high hence there is a need for established public health interventions that can lead to a reduction of HBV vertical transmission. Treatment of pregnant women with HBV chronic infection using anti-viral medications during pregnancy might curb the vertical transmission rates.

Seroprevalence and associated risk factors for hepatitis B virus among pregnant women attending health facility in Osogbo, Nigeria

Background Hepatitis B virus (HBV) infection among pregnant women has a high rate of vertical transmission and consequential effects on fetal and neonatal outcomes. The aim of this study was to determine the prevalence and associated risk factors of infection among pregnant women attending antenatal care services in Osogbo, Nigeria. Methodology This hospital based cross-sectional study was conducted among pregnant women attending routine antenatal care clinic between April and June 2021. Systematic random sampling technique was used to recruit 240 pregnant women, their data were collected by face to face interview using a pretested questionnaire, while blood sample was collected aseptically to determine hepatitis B surface antigen by enzyme linked immunosorbent assay test kit. Univariate and multivariate logistic regression were used to examine the association between explanatory variables and outcome variable. Results The mean age and seroprevalence of the study population were 27.50 ± 4.4 years and 5.8% respectively. The significant risk factors for HBV infection were tattooing (aOR = 5.22; 95% CI = 0.52­8.01; p = 0.0000), history of multiple sexual partners (aOR = 2.88; 95% CI = 1.92­12.42; p = 0.0044); and past history of contact with HBV patient (aOR = 2.17; 95% CI = 1.21­15.32; p = 0.0310) were significant predictors of HBV infection. Conclusion The seroprevalence of HBV from this study was of intermediate endemicity. We therefore, advocate for continuous health education programs on the mode of HBV transmission, high-risk behaviors and methods of preventions at antenatal care clinics to raise the awareness of mothers and limit the spread of infection.

Prévalence de l'infection par l'hépatite virale B et facteurs associés chez les enfants des sujets ivoiriens porteurs de l'AGHBS / Prevalence of hepatitis B infection and factors associated in children of Ivorian HBsAg carrier

Objectifs : Déterminer la prévalence de l'infection par le virus de l'hépatite B (VHB) chez les enfants (sujets contact) des sujets porteurs chroniques de l'Ag HBs (sujets index) et rechercher les facteurs associés à cette infection chez ces enfants.Patients et méthodes: il s'est agi d'étude rétrospective transversale portant sur les patients positifs pour l'Ag HBs (sujets index), dont la famille (sujets contact: conjoints et enfants) a été soumise à un dépistage systématique de l'infection par le VHB. Résultats: L'âge médian de nos 44 sujets était de 43,1 ± 7,49 ans. Le nombre moyen d'enfants par sujet index était de 2,3 ± 1,1. L'âge médian des 92 enfants était de 9,3 ± 4,55 (de 1 à 15 ans) et 43 (44,8%) étaient vaccinés contre le VHB. La fréquence de l'infection par le VHB était de 24%. Les facteurs indépendants associés à l'infection par le VHB chez les enfants étaient l'ADN du VHB pour les sujets index> 2000 UI/ml (OR = 11,5; p = 0,001), l'existence du VHB chez les deux parents (OR = 7,9; p = 0,03) et l'absence de vaccination contre le VHB chez les enfants (OR = 30,9; p = 0,003). Conclusion: La couverture vaccinale des enfants des sujets index était insuffisante. Outre la transmission verticale, le risque de transmission intrafamiliale était élevé en présence d'au moins un des trois facteurs associés

Objectives: To determine the prevalence of hepatitis B virus (HBV) infection in children (contact subjects) of chronic HBsAg (index subjects) and to investigate the factors associated with this infection in these children. Patients and methods: this was a retrospective cross-sectional study of HBsAg positive patients (index subjects), whose families (contact subjects: spouses and children) were routinely screened for HBV infection. Results: The median age of our 44 subjects was 43.1 ± 7.49 years. The average number of children per index subject was 2.3 ± 1.1. The median age of the 92 children was 9.3± 4.55 (1 to 15 years) and 43 (44.8%) were vaccinated against HBV. The prevalence of HBV infection was 24%. The independent factors associated with HBV infection in children were HBV DNA for index subjects> 2000 IU/ml (OR = 11.5; p = 0.001), the existence of HBV in both parents (OR = 7.9; p = 0.03) and no HBV vaccination in children (OR = 30.9; p = 0.003). Conclusion: Immunization coverage of children of index subjects was insufficient. In addition to vertical transmission, the risk of intrafamilial transmission was high in the presence of at least one of the three associated factors.

Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study / 中华肝脏病杂志

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

Persistence follow-up of immune memory to hepatitis B vaccine among infants with non- and low-response to primary vaccination after revaccination with three doses / 中华预防医学杂志

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.

Research progress of biomarkers of hepatitis B virus and clinical significance / 生物医学工程学杂志

The infection of Hepatitis B virus (HBV) can result in severe consequences, including chronic hepatitis, liver fibrosis, cirrhosis, and even liver cancer. Effective antiviral treatment has the potential to slow down the progression of the disease. HBV serum biomarkers play a crucial role in the dynamic management of chronic hepatitis B (CHB) patients. However, the conventional hepatitis B virus markers, such as hepatitis B serologic testing and HBV DNA, are insufficient to meet the clinical requirements. This review provided a comprehensive overview of the current research on the quantification of HBsAg and anti-HBc, HBV RNA and HBV core-associated antigen, which summarized the crucial role these markers play in the administration of antiviral medications, predicting the efficacy of treatment and anticipating the likelihood of virologic rebound following drug cessation, as well as assessing disease progression in CHB patients.

Epidemiological survey of hepatitis B and analysis of hepatitis B vaccine coverage rate among children aged 1-14 years in Lhasa in 2006, 2014 and 2020 / 中华预防医学杂志

In 2006, 2014 and 2020, the positive rates of HBsAg in 560, 384 and 402 children aged 1 to 14 years were 4.5%, 2.6% and 2.5%, respectively, with no statistically significant differences (P>0.05). The positive rate of anti-HBs was highest in 2014 (57.8%) and lowest in 2006 (34.1%) (P<0.05). The positive rate of anti-HBc was highest in 2006 (15.7%), and decreased in 2014 (7.8%) and 2020 (5.7%) (P<0.001). The timely rate of the first dose of hepatitis B vaccine for children in Lhasa in 2006, 2014 and 2020 was 7.7% (43/560), 50.3% (193/384) and 94.8% (381/402), respectively. The overall vaccination rates were 15.4% (86/560), 35.2% (135/384) and 96.0% (386/402), respectively, showing a trend of gradual increases (χtrend values were 718.63 and 589.59, both P values<0.001).

Incidence and factors associated with hepatitis B surface antigen seroclearance in patients co-infected with HBV/HIV during antiretroviral therapy in Guangdong, China / 中华医学杂志(英文版)

BACKGROUND@#Hepatitis B surface antigen (HBsAg) clearance is vital for a functional cure of hepatitis B virus (HBV) infection. However, the incidence and predictors of HBsAg seroclearance in patients co-infected with HBV and human immunodeficiency virus (HIV) remain largely unknown in Guangdong, China.@*METHODS@#Between 2009 and 2019, patients co-infected with HBV/HIV undergoing antiretroviral therapy (ART) in Guangzhou Eighth People's Hospital affiliated to Guangzhou Medical University were retrospectively reviewed with the endpoint on December 31, 2020. The incidence and risk factors for HBsAg seroclearance were evaluated using Kaplan-Meier and multivariate Cox regression analyses.@*RESULTS@#A total of 1550 HBV/HIV co-infected patients were included in the study, with the median age of 42 years and 86.0% (1333/1550) males. Further, 98.3% (1524/1550) received ART containing tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC). HBV DNA was examined in 1283 cases at the last follow-up. Over the median 4.7 years of follow-up, 8.1% (126/1550) patients achieved HBsAg seroclearance, among whom 50.8% (64/126) obtained hepatitis B surface antibody, 28.1% (137/488) acquired hepatitis B e antigen seroconversion, and 95.9% (1231/1283) undetectable HBV DNA. Compared with patients who maintained HBsAg positive, cases achieving HBsAg seroclearance showed no differences in age, gender, CD4 + T cell count, alanine aminotransferase (ALT) level, or fibrosis status; however, they presented lower HBV DNA levels, lower HBsAg levels, and higher rates of HBV genotype B at the baseline. Multivariate analysis showed that baseline HBsAg <1500 cutoff index (COI) (adjusted hazard ratio [aHR], 2.74, 95% confidence interval [95% CI]: 1.48-5.09), ALT elevation >2 × upper limit of normal during the first six months after receiving ART (aHR, 2.96, 95% CI: 1.53-5.77), and HBV genotype B (aHR, 3.73, 95% CI: 1.46-9.59) were independent predictors for HBsAg seroclearance (all P <0.01).@*CONCLUSIONS@#Long-term TDF-containing ART has high anti-HBV efficacy including relatively high overall HBsAg seroclearance in HBV/HIV co-infected patients. Lower baseline HBsAg levels, HBV genotype B, and elevated ALT levels during the first six months of ART are potential predictors of HBsAg seroclearance.

Kashmiri refugees at the verge of hepatitis B and C epidemic in the State of Azad Jammu and Kashmir, Pakistan

ABSTRACT OBJECTIVE To determine the seroprevalence of hepatitis B and C among immigrants residing refugee camps in Muzaffarabad, Azad Kashmir, Pakistan, and to identify possible risk factors for hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission. METHODS Around 1,225 individuals inhabiting Muzaffarabad refugee camps, participated in the study. A qualitative Immuno-Chromatographic Technique was used for initial screening and PCR test was used for detection of HBV and HCV in participants. The major risk factors for HBV and HCV transmission were assessed using a questionnaire approach. RESULTS Around 86 (7.0%) individuals were observed for hepatitis B surface antigen (HBsAg) presence, and 215 (17.5%) individuals were found positive for Anti-HCV. Only 32 (2.6%) individuals were confirmed for HBV DNA and 126 (10.3%) individuals were positive for HCV RNA after PCR. Demographically, both HBsAg and Anti-HCV were found more prevalent in female (4.4% HBsAg and 10.8% Anti-HCV) population as compared to male (2.6% HBsAg and 6.7% Anti-HCV) population. Surprisingly, the HBsAg (23.5%) and Anti-HCV (41.1%) appeared to be more frequent in the age group 62-75 years. Previous history of hepatitis in the family (p < 0.0001), blood transfusion (p = 0.0197) dental treatment (p < 0.0001) and tattooing or piercing on any part of the body (p = 0.0028) were assessed as significant risk factors in HBV and HCV transmission. CONCLUSIONS Presence of 7.0% HBsAg and 17.5% Anti-HCV in a small fragment of the migrant population cannot be overlooked. Lack of awareness among people and negligence of health department could escalate the situation.

Sero-prevalence of Hepatitis B virus surface antigen and associated factors among women of reproductive age in Bench Maji Zone, Southwest Ethiopia: community based cross-sectional study

Background: Hepatitis B virus infection is one of the leading causes of liver diseases which occurs worldwide particularly in developing countries. It is often caused by prenatal transmission from mother to child or household transmission from a close contact during early childhood. It causes different complications like; jaundice, induces premature labor, and prematurity. Objective: The aim of this study was to estimate the sero-prevalence of hepatitis B virus surface antigen and associated factors among women of reproductive age in Bench Maji Zone, South West Ethiopia. Methods: A community-based cross-sectional study was conducted from December 15th, 2016 to February 15th, 2017. Multistage sampling technique was applied to select study participants. Logistic regression analysis was applied and p-values < 0.05 was used to see the significant association between dependent and independent variables. Results: A total of 330 participants were included in this study yielding 98.8% response rate. The sero-prevalence of HBsAg among women of reproductive age was 28(8.5%). Having multiple sexual partners (AOR = 18.73, 95% CI =3.65, 96.21) history of unprotected sex (AOR = 9.39, 95% CI =1.64, 53.77) were found to be significantly associated with sero-prevalence of HBV. Conclusions: The sero-prevalence of HBV infection among women of reproductive age was highly endemic. Hence, behavioral education and communication programs focusing on reduction of risky sexual behaviors should be designed to reduce HBV infection.

Epidemiology of hepatitis B virus infection among pregnant women in Lubumbashi, Democratic Republic of Congo: prevalence, risk factors, and genotype distribution

Background Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a significant public health problem. Most children under five years living with HBV in endemic areas like sub-Slivingan Africa. Vertical transmission is considered the main newborn's route of contamination, which leads in 90% of cases to the chronic stage of the disease. Objectives To determine the seroprevalence and identify risk factors of carrying hepatitis B surface Antigen (HBsAg) in pregnant women, assess biochemical parameters, and study the distribution of HBV genotypes among infected pregnant women in Lubumbashi. Methods This was a cross-sectional descriptive and experimental study in which 1711 pregnant women were recruited. The study took place in the hospital Jason Sendwe of Lubumbashi. A pre-established epidemiological survey form was used to collect data from the study population. Results The seroprevalence of HBV among pregnant women was 4.4%. Blood transfusion and unprotected sex have been associated with the risk of carrying HBsAg. Increased levels of bilirubin and transaminases were observed. The genotypes E (59.4%), A (40.6%), and a few drug resistance mutations were identified in the study population. Conclusion With an HBV seroprevalence of 4.4%, MTCT of HBV remains a public health concern in Lubumbashi. This result highlights the vital role of HBV screening in pregnant women and newborns and early HBV vaccination. In addition, the obtained HBV genotyping data could help better understand the local epidemiology of the disease, predict the outcome of the Antiviral therapy, and develop a mapping of HBV genotypes in Lubumbashi.

Geranyl phenyl ethers from Illicium micranthum and their anti-HBV activity / 中国天然药物

Fourteen new geranyl phenyl ethers (1-14) along with three known compounds (15-17) were isolated from Illicium micranthum, and their structures were elucidated by comprehensive spectroscopic methods. Illimicranins A-H (1-8) were characterized as geranyl vanillin ethers, while 9 and 10 were dimethyl acetal derivatives. Illimicranins I and J (11 and 12) were rare geranyl isoeugenol ethers. Illimicranins K and L (13 and 14) represented the first example of geranyl guaiacylacetone ether and geranyl zingerone ether, respectively. Compounds 1, 2 and 15 exhibited anti-HBV (hepatitis B virus) activity against HBsAg (hepatitis B surface antigen) and HBeAg (hepatitis B e antigen) secretion, and HBV DNA replication.

Study on Reentry Evaluation Mode for Blood Donors Used to be HBV Reactive in Jiangsu Province / 中国实验血液学杂志

OBJECTIVE@#To evaluate the risk of reentry in HBV reactive blood donors and feasibility of HBV reentry strategy.@*METHODS@#HBsAg+ or HBV DNA+ donors who had been quarantined for more than 6 months in Jiangsu Province could propose for reentry application. Blood samples were routinely screened by dual-ELISA for HBsAg, anti-HCV, HIV Ab/Ag, and anti- Treponema pallidum and those non-reactive ones were tested by minipool nucleic acid testing (NAT) for three times. To identify occult HBV donors, samples of NAT non-reactive were further tested by electrochemiluminescence immunoassay (ECLIA) for HBV seromarkers (including HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb). Donors of only 4 ECLIA patterns were accepted to reentry, including all 5 HBV seromarkers negative, anti-HBs only but having history of hepatitis B vaccine injection, HBcAb only, HBsAb+ / HBcAb+ with HBsAb more than 200 IU/L. Additionally, the detection rate of HBV infection was compared between routine screening mode and ECLIA, as well as the reentry qualified rate of HBsAg+ and HBV DNA+ blood donors.@*RESULTS@#From Oct. 2016 to Aug. 2019, a total of 737 HBV reactive donors had applied for reentry, including 667 HBsAg+ reactive and 70 HBV DNA+ reactive donors. Among 3 screening methods, the highest HBV detection rate (43.15%, 318/737) was observed on ECLIA, while only 4.75% (35/737) on ELISA and 3.12% (23/737) on NAT, respectively. Among 4 qualified patterns of HBV serological markers, the highest proportion was found in the all negative group (22.90%, 155/677), followed by the group with HBsAb+ only and history of hepatitis B vaccine injection (19.35%, 131/677), and the median concentration of HBsAb was 237.7 IU/L. The unqualified rate of HBV DNA+ donors was 82.86%, which was significantly higher than 47.98% of HBsAg+ donors.@*CONCLUSION@#Routine screening tests merely based on ELISA and NAT could miss occult HBV donors and may not be sufficient for blood safety. HBsAb concentration and vaccine injection history should be included in the evaluation of HBV reactive donors who intend to apply for reentry. There is a relatively larger residual risk of occult HBV infection in blood donors quarantined for HBV DNA reactive.

Rational selection of virologic and immunological biomarkers and therapeutic endpoints in the clinical trials of new drugs treating chronic hepatitis B / 中华肝脏病杂志

Hepatitis B virus (HBV) infection remains to be the major cause of chronic liver diseases in China. Since the nucleos(t)ide analogues and pegylated interferon-alpha do not directly target the covalently closed circular DNA (cccDNA) in the nuclei of HBV-infected hepatocytes, those standard-of-care medications cannot efficiently cure the infected hepatocytes and rarely achieve the functional cure of chronic hepatitis B (CHB). Therefore, new antiviral drugs targeting distinct steps of HBV replication and immunotherapeutics reinvigorating antiviral immune responses are urgently needed for the functional cure of CHB. Based on the extensive discussion of the biological and clinical significance of new virologic biomarkers and distinct mechanism of drug candidates currently in clinical development, we propose that the selection of virologic and immunological biomarkers for evaluation of therapeutic efficacy as well as setting the therapeutic endpoints in the clinical trials should be based on the mode of action of investigational drugs. In addition, due to the complexity of CHB pathogenesis, selection of specific subpopulation of CHB patients for the clinical trials of drugs with a specific mode of action should also be considered.

Expert opinion on expanding anti-HBV treatment for chronic hepatitis B / 中华肝脏病杂志

To meet the unmet medical needs and better reflect the new clinical evidence of chronic hepatitis B management, Chinese Society of Hepatology developed expert consensus on expanding diagnosis and treatment in China. The recommendations include to expand HBsAg screening in the population and HBV DNA detection by sensitive quantitative real-time PCR (qPCR), decrease the alanine aminotransferase (ALT) threshold for treatment of chronic hepatitis B, and promptly start antiviral therapy in the patients who are at risk of disease progression, and appropriately manage the patients with low level viremia.

A study of the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg- positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA / 中华肝脏病杂志

Objective: To investigate the effectiveness of nucleos(t)ide analogues in the treatment of HBeAg-positive chronic hepatitis B with normal alanine aminotransferase and high level of HBV DNA. Methods: Treatment-naïve chronic hepatitis B patients who were followed up at the Center of Infectious Diseases, West China Hospital of Sichuan University from January 2019 to January 2020 were selected as subjects. Demographic characteristics, the results of laboratory examination before treatment and one year after treatment were retrospectively collected. Patients were divided into tenofovir dipivoxil (TDF) and propofol fumurate tenofovir (TAF) treatment group according to different types of medication. The changes of serum HBV DNA level, HBeAg serological conversion and HBsAg quantitative level were analyzed and compared between the two groups. Results: A total of 38 cases were enrolled. Among them, there were 16 and 22 cases in the TDF and TAF group, respectively. There was no statistically significant difference in demographic characteristics, baseline HBV DNA levels and HBsAg quantitative levels between the two groups. Virological response was achieved in 60.5% (23/38) of patients after one year of antiviral therapy. Serum HBV DNA levels below the lower limit of detection [68.2% (15/22) vs. 50.0% (8/16), P=0.258] and higher HBeAg seroconversion rate [18.2%] (4/22) vs. 6.3% (1/16), P=0.374] was obtained in TAF than TDF group; however, there was no statistically significant differences between the two. Serum HBsAg quantitative level was significantly reduced with TDF and TAF treatment. In addition, alanine aminotransferase elevation was reduced in TAF than TDF treated group. Multivariate logistic regression analysis showed that patient age was an independent predictor of a virological response to antiviral therapy. Conclusion: HBeAg-positive CHB patients with normal alanine aminotransferase, and high HBV DNA level can obtain better curative effect after TDF and TAF treatment.

Observation of PD-1+CXCR5+CD4+T lymphocyte and sPD-1 levels in HBeAg positive chronic hepatitis B virus carriers treated with entecavir / 中华肝脏病杂志

Objective: To dynamically observe the clinical efficacy of entecavir and the changes of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 levels in peripheral blood of HBeAg-positive chronic hepatitis B virus carriers treated with entecavir, and further explore its clinical significance. Methods: There were 31 cases of chronic hepatitis B virus carriers in the treatment group (A), 32 cases of chronic hepatitis B virus carriers in the treatment group (B), and 15 cases of chronic hepatitis B virus carriers in the non-treatment group (C).Three groups peripheral blood samples and clinical data at 0, 24 and 48 weeks were collected and compared. PD-1+CXCR5+CD4+T lymphocytes were detected by flow cytometry, and the level of sPD-1 was detected by enzyme-linked immunosorbent assay. ANOVA and Spearman correlation analysis were performed on the measurement data among the three groups. Results: At week 0, the serum levels of HBsAg, HBeAg and HBV DNA were significantly higher in groups A and C than group B. PD-1+CXCR5+CD4+T lymphocytes in peripheral blood were significantly higher in group B (4.70%±1.58%) than group A (3.25%±1.01%) and group C (2.77%±0.67%) (F=16.65, P<0.05). There was no significant difference between group A and group C (P>0.05). Peripheral blood sPD-1 in group B [(1 866.62±1 472.70) pg/ml] was significantly higher than group A [(824.86±538.66) pg/ml] and group C [(618.19±602.62) pg/ml] (F=10.95, P<0.05). There was no significant difference between group A and group C (P>0.05). At 48 weeks, the serum HBsAg did not decrease significantly in groups A and C than baseline (P>0.05), but were significantly higher than group B (P<0.05). Serum HBeAg levels were decreased significantly in groups A and B than baseline (P<0.05). <0.05), but group A was significantly higher than group B (P<0.05), and there was no significant difference between group A and group C (P>0.05). Serum HBV DNA level was significantly lower in groups A and B than group C (P<0.05), and there was no significant difference between group A and group B (P>0.05). Peripheral blood PD-1+CXCR5+CD4+T lymphocytes were significantly lower in Group A (1.56%±0.73%) and group B (1.32%±0.43%) than group C (2.64%±0.85%) (P<0.05). Peripheral blood sPD-1 were significantly lower in group A [(289.05±215.86) pg/ml] and group B [(236.01±173.92) pg/ml] than group C [(650.34±598.46) pg/ml] (P<0.05). There was no significant difference between group A and group B. Correlation analysis results: In group A at 48 weeks, the decreased level of PD-1+CXCR5+CD4+T lymphocyte ratio had no correlation with the decreased level of HBsAg and HBV DNA, but was positively correlated with the decreased level of HBeAg (r=0.376, P<0.05). The decreased level of sPD-1 had no correlation with the changes of HBsAg, but was positively correlated with the decreased levels of HBeAg and HBV DNA (r=0.598 and 0.384, P<0.05). In group B at 48 weeks, the decreased levels of PD-1+CXCR5+CD4+T lymphocytes and sPD-1 were positively correlated with the decreased levels of HBsAg, HBeAg, and HBV DNA (P<0.05). Conclusion: Hepatitis B virus replication and expressions in HBeAg-positive chronic hepatitis B virus carriers were significantly inhibited after 48 weeks of antiviral treatment, which is related not only to entecavir treatment, but also to the immunological mechanism involved in sPD-1. Moreover, the inhibition of HBeAg expression is associated with a decrease in the number and/or activity of PD-1+CXCR5+CD4+T lymphocytes.

Study on the relationship between nonalcoholic fatty liver disease and hepatocellular carcinoma in patients with prior hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of nonalcoholic fatty liver disease (NAFLD) in the development of hepatocellular carcinoma (HCC) in patients with prior hepatitis B virus infection (HBsAg-negative and anti-HBC-positive). Methods: 1605 hospitalized patients who were first diagnosed with HCC at Nanfang Hospital between 2015 to 2017 were retrospectively studied. Patients who developed HCC on the basis of active HBV infection (HBsAg-positive, anti-HBc positive) were used as control. Multivariate logistic regression model was used to analyze the relationship between NAFLD and HCC in patients with prior hepatitis B virus infection. Results: Among HCC patients with both HBsAg and anti-HCV negative, the proportion of prior HBV infection accounted for 86.7%. NAFLD prevalence was higher in patients with HCC based on prior HBV infection than active HBV infection (19.7% vs. 8.5%, P < 0.001). After adjusting for gender, age, hypertension, alanine aminotransferase, and liver cirrhosis, patients with HCC based on prior HBV infection were more likely to develop NAFLD (OR: 2.29, 95% CI: 1.40-3.74), and this phenomenon was observed only in patients with non-cirrhosis (OR: 5.26, 95% CI: 2.53-10.96) and aged≥50 years (OR: 2.36, 95% CI: 1.33-4.20). Conclusion: NAFLD may be a risk factor for HCC in a previously infected patients with HBV, especially in non-cirrhotic and population aged≥50 years.

Distributive characteristics of HBV DNA CpG islands in HBsAg positive mothers and its relationship with intrauterine transmission / 中华流行病学杂志

Objective: To investigate the type, length, and CG loci of HBV DNA CpG islands in HBsAg positive maternal C genotype and its relationship with intrauterine HBV transmission, so as to provide a new perspective for the study of intrauterine transmission of HBV. Methods: From June 2011 to July 2013, HBsAg-positive mothers and their newborns who delivered in the obstetrics and gynecology department of the Third People's Hospital of Taiyuan were collected. Epidemiological data were collected through face-to-face questionnaires and electronic medical records. Serum HBV markers and serum HBV DNA were detected by electrochemiluminescence and quantitative fluorescence PCR, respectively. Intrauterine transmission of HBV was determined by positive HBsAg and/or HBV DNA in femoral venous blood before injection of HBV vaccine/Hepatitis B immunoglobulin within 24 h of birth. A total of 22 mothers and their newborns with HBV DNA load ≥106 IU/ml in intrauterine transmission were selected as the intrauterine transmission group, and 22 mothers with HBV DNA load ≥106 IU/ml without intrauterine transmission were chosen as the control group by random seed method. The distribution prediction of CpG islands of HBV DNA in 39 mothers with genotype C by HBV DNA sequencing was analyzed. Results: Among 39 mothers with HBV C genotype, 19 were in the intrauterine transmission group, and 20 were in the control group. The HBV DNA of 39 patients with genotype C traditional CpG island Ⅱ and Ⅲ, while the control group had traditional CpG island Ⅰ and novel CpG island Ⅳ and Ⅴ. The length of CpG island Ⅱ and Ⅲ and the number of CG loci of CpG island Ⅱ in the intrauterine transmission group differed from those in the control group (P<0.05). The CpG island Ⅱ length ≥518 bp and the number of CG loci ≥40 in the intrauterine transmission group (11/19) were significantly higher than those in the control group (2/20) (P<0.05). The length of CpG island Ⅱ and the number of CG loci in the X gene promoter region (Xp region) were higher than those in the control group (P<0.05). In the HBV intrauterine transmission group, most of maternal (12/19) HBV DNA CpG island Ⅱ completely covered the Xp region, which was significantly higher than that in the control group (5/20), and the number of HBV DNA Xp region CG loci was higher than that in the control group (P<0.05). Conclusions: The distribution of maternal C genotype HBV DNA CpG islands is related to intrauterine transmission. The length of CpG island Ⅱ and the number of CG sites may increase the risk of intrauterine transmission of HBV.

Non/hypo-response to hepatitis B vaccination and influencing factors in HIV-infected patients in the context of different immunization schedules / 中华流行病学杂志

Objective: To study the non/hypo-response to hepatitis B vaccination in HIV-infected patients, identify the influencing factors and provide evidence for the development of hepatitis B prevention and control strategies and measures for special population. Methods: On the basis of the randomized controlled trial of 20 µg hepatitis B vaccine immunization at 0-1-6 month, 0-1-2-6 month and 60 µg hepatitis B vaccine immunization at 0-1-2-6 month, the HIV-infected patients who completed one-month follow-up after the full course vaccination were selected as study subjects. Quantification of antibody to hepatitis B surface antigen (anti-HBs) in serum samples was performed by using chemiluminescent microparticle immunoassay (CMIA) and demographic characteristics, disease history, HIV infection and treatment status of the study subjects were collected. Statistical analysis was conducted by χ2 test, t test, unconditional logistic regression and interaction analyses. Results: The non/hypo-response rates to hepatitis B vaccination were 34.65% (35/101), 24.49% (24/98) and 10.99% (10/91) in 20 µg group at 0-1-6 month or 0-1-2-6 month and 60 µg group at 0-1-2-6 month (P<0.001), respectively. Logistic regression analysis showed that after controlling for confounding factors, the risk for non/hypo-response was 0.22 times higher in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in patients receiving 20 µg hepatitis B vaccine at 0-1-6 month (95%CI: 0.10-0.50), the risk for non/hypo-response was higher in men than in women (OR=3.65, 95%CI: 1.88-7.07), and the risk for non/hypo-response was 2.64 times higher in those without hepatitis B vaccination history than in those with hepatitis B vaccination history (95%CI: 1.10-6.32). Moreover, there were multiplicative interactions between immunization schedule and gender (OR=2.49, 95%CI: 1.24-5.00). Conclusion: The non/hypo-response rate to hepatitis B vaccination was significantly lower in HIV-infected patients receiving 60 µg hepatitis B vaccine at 0-1-2-6 month than in those receiving 20 µg hepatitis B vaccine at 0-1-6 month and 0-1-2-6 month. Gender, vaccination schedule and history of hepatitis B vaccination were the influencing factors of the non/hypo-response to hepatitis B vaccination. There was a multiplicative interaction between vaccination schedule and gender, and men receiving 20 µg hepatitis B vaccines had a higher risk for non/hypo-response to hepatitis B vaccination.