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.
Child ; Humans ; Infant ; Hepatitis B Vaccines ; Immunization, Secondary ; Hepatitis B Surface Antigens ; Immunologic Memory ; Follow-Up Studies ; Vaccination ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies

Humans ; Hepatitis B Surface Antigens ; Hepatitis B/drug therapy* ; Hepatitis B virus/genetics* ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/diagnosis* ; DNA, Viral

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.
Humans ; Male ; Female ; Adult ; Aged, 80 and over ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/epidemiology* ; Hepatitis B e Antigens ; Hepatitis B/drug therapy* ; Hepatitis B Surface Antigens ; Hepatitis A ; Liver Cirrhosis/drug therapy* ; China/epidemiology* ; Registries ; Hepatitis B virus/genetics* ; DNA, Viral

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).
Child ; Humans ; Hepatitis B Vaccines ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B Antibodies ; Vaccination

As main recipient cells for porcine reproductive and respiratory syndrome virus (PRRSV), porcine alveolar macrophage (PAM) are involved in the progress of several highly pathogenic virus infections. However, due to the fact that the PAM cells can only be obtained from primary tissues, research on PAM-based virus-host interactions remains challenging. The improvement of induced pluripotent stem cells (iPSCs) technology provides a new strategy to develop IPSCs-derived PAM cells. Since the CD163 is a macrophage-specific marker and a validated receptor essential for PRRSV infection, generation of stable porcine induced pluripotent stem cells lines containing CD163 reporter system play important roles in the investigation of IPSCs-PAM transition and PAM-based virus-host interaction. Based on the CRISPR/Cas9- mediated gene editing system, we designed a sgRNA targeting CD163 locus and constructed the corresponding donor vectors. To test whether this reporter system has the expected function, the reporter system was introduced into primary PAM cells to detect the expression of RFP. To validate the low effect on stem cell pluripotency, we generated porcine iPSC lines containing CD163 reporter and assessed the pluripotency through multiple assays such as alkaline phosphatase staining, immunofluorescent staining, and EdU staining. The red-fluorescent protein (RFP) expression was detected in CD163-edited PAM cells, suggesting that our reporter system indeed has the ability to reflect the expression of gene CD163. Compared with wild-type (WT) iPSCs, the CD163 reporter-iPSCs display similar pluripotency-associated transcription factors expression. Besides, cells with the reporter system showed consistent cell morphology and proliferation ability as compared to WT iPSCs, indicating that the edited-cells have no effect on stem cell pluripotency. In conclusion, we generated porcine iPSCs that contain a CD163 reporter system. Our results demonstrated that this reporter system was functional and safe. This study provides a platform to investigate the iPS-PAM development and virus-host interaction in PAM cells.
Swine ; Animals ; Induced Pluripotent Stem Cells/metabolism* ; Receptors, Cell Surface/genetics* ; Antigens, CD/metabolism* ; Porcine respiratory and reproductive syndrome virus/genetics*

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.
Humans ; Hepatitis B virus/genetics* ; Clinical Relevance ; Hepatitis B, Chronic/drug therapy* ; Hepatitis B Core Antigens/therapeutic use* ; Biomarkers ; Liver Cirrhosis/drug therapy* ; Antiviral Agents/therapeutic use* ; Hepatitis B Surface Antigens/therapeutic use* ; DNA, Viral/therapeutic use* ; Hepatitis B e Antigens/therapeutic use* ; Hepatitis B/drug therapy*

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.
Male ; Humans ; Adult ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; HIV Infections/drug therapy* ; HIV ; DNA, Viral ; Incidence ; Coinfection/drug therapy* ; Retrospective Studies ; Tenofovir/therapeutic use* ; Lamivudine/therapeutic use* ; Hepatitis B, Chronic/drug therapy*

Humans ; Consensus ; East Asian People ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatitis B/virology* ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B virus/physiology* ; Virus Activation ; Latent Infection/virology*

Objective: To estimate the effectiveness of the primary screening strategy for liver cancer in rural areas to provide basic information for the optimization and perfection of the technical program for the early detection and treatment of liver cancer. Methods: Residents including males aged 35-64 and females aged 45-64 from 9 counties in rural China between 2013 and 2015 were selected as the target population. The participant was classified into a high-risk and non-high-risk group based on the standardized questionnaire or HBsAg, and the Chi-squared test was applied to compare differences between the two groups. The Cox proportional hazard regression models were applied to assess hazard ratio (HR) and its 95% confidence interval (CI). Results: 358 348 participants were recruited from 2013 to 2015. 1 196 individuals were identified with liver cancer until December 31, 2021, with an incidence density of 52.0/10(5) person-years. Of the participants, 54 650 were assessed as high risk (15.3%) based on the questionnaire and the status of HBsAg. The high-risk population had a higher incidence density (168.3/10(5) person-years vs 31.5/10(5) person-years) and higher risk of developing liver cancer (HR=2.98, 95% CI=2.64-3.35), compared to the non-high-risk group. Based on the questionnaire-based high-risk assessment system, 47 884 (13.4%) individuals were identified as high risk, who showed statistical differences in terms of incidence density and incidence risk, in comparison to the low-risk population (all P<0.05). HBsAg can screen out a higher proportion of high-risk individuals who are women, non-smokers, non-drinkers, and individuals without a family history of liver cancer (all P<0.05). The sensitivity analysis of the effectiveness of the whole primary screening method is stable, and high-risk individuals still had a higher risk of liver cancer. Conclusions: The primary screening method of the questionnaire-based risk assessment system and HBsAg can achieve satisfactory effectiveness. The questionnaire-based risk assessment system could identify high-risk individuals to some extent, however, it still needs to be improved to meet the actual requirements.
China/epidemiology* ; Early Detection of Cancer ; Female ; Hepatitis B Surface Antigens ; Humans ; Incidence ; Liver Neoplasms/epidemiology* ; Male ; Mass Screening ; Risk Factors

Objective: To analyze the impact of metabolic risk factors on the epidemiological characteristics of the reactivation of inactive HBsAg carriers (IHC) and provide effective intervention measures to standardize the management of chronic hepatitis B infections. Methods: Based on the chronic hepatitis B infection cohort established in 2010 in Jiangsu province, six follow-up visits from 2012 to 2020 were conducted to analyze the characteristics and influencing factors of the hepatitis B reactivation of IHC and the impact of metabolic risk factors, including obesity, high blood pressure, diabetes and hyperglycemia. Results: From 2012 to 2020, 2 527 IHC and 17 730 person-years were observed during a median follow-up period of 7.0 person-years. Ninety-eight cases of hepatitis B reactivation, with a cumulative reaction rate, was 3.9%, and the incidence density was 5.53/1 000 person-years. Multivariate Cox proportional risk regression analysis showed that age and baseline HBV DNA were independent risk factors of HBV reactivation. Compared with the patients ≥60 years, 40-49 age group (aHR=2.16, 95%CI:1.20-3.90) and 20-29 age group (aHR=5.48, 95%CI:2.07-14.48) were significantly associated with hepatitis B reactivation. Compared with the HBV DNA negative patients at baseline, the risk of hepatitis B reactivation was higher in the group with low HBV DNA level 100-1 999 IU/ml (aHR=1.67, 95%CI:1.11-2.52). Stratification analysis results showed that compared with those without metabolic risk factors, in the ≥50 age group, patients with ≥2 metabolic risk factors showed adjusted HR of 2.73 (95%CI:1.08-6.96). Conclusions: The risk of hepatitis B being reactive is the persistent existence of IHC in communities in Jiangsu province, especially young adults, low-level HBV DNA carriers, and IHC with ≥2 metabolic risk factors. Follow-up for these IHC should be strengthened to reduce the risk of disease progression by antiviral treatment at the right time.
Cohort Studies ; DNA, Viral ; Hepatitis B/epidemiology* ; Hepatitis B Surface Antigens ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/epidemiology* ; Humans ; Risk Factors ; Young Adult