Objective:b> To explore the immunogenicity and influencing factors of hepatitis B vaccination based on different vaccination schedules among chronic kidney disease (CKD) patients. Methods:b> CKD patients who participated in randomized controlled trials in four hospitals in Shanxi province and completed three doses of 20 µg vaccination (at months 0, 1 and 6) and four doses of 20 µg or 60 µg vaccination (at months 0, 1, 2, and 6) were surveyed from May 2019 to July 2020.According to the ratio of 1∶1∶1, 273 CKD patients were divided into 3 groups randomly. Quantification of the anti-hepatitis B surface antigen-antibody (anti-HBs) in serum samples was performed using chemiluminescent microparticle immunoassay at months 1 and 6 after the entire course of the vaccinations. The positive rate, high-level positive rate, geometric mean concentration (GMC) of anti-HBs, and the influencing factors were analyzed by χ² tests, analysis of variance, unconditional logistic regression analysis. Results:b> A total of 273 CKD patitents were participants.The positive rates in the CKD patients with four doses of 20 µg vaccination (92.96%,66/71) or 60 µg vaccination (93.15%, 68/73) were higher than that in the CKD patients with three doses of 20 µg vaccination (81.69%, 58/71) at month one after the full course of the vaccinations (P<0.05). The GMCs of anti-HBs showed similar results (2 091.11 mIU/ml and 2 441.50 mIU/ml vs. 1 675.21 mIU/ml) (P<0.05). The positive rate was higher in the CKD patients with four doses of 60 µg vaccination (94.83%,55/58) than in those with three doses of 20 µg vaccination (78.79%,52/66) (P<0.05) at month six after the full course of the vaccinations. And the GMC of anti-HBs in the patients with four doses of 60 µg vaccination (824.28 mIU/ml) was significantly higher than those in the patients with 3 or 4 doses of 20 µg vaccination (639.74 mIU/ml and 755.53 mIU/ml) (P<0.05). After controlling the confounding factors, the positive rate in the CKD patients with four doses of 60 µg vaccination were 3.19 (95%CI: 1.02-9.96) and 5.32 (95%CI: 1.27-22.19) times higher than those in the patients with three doses of 20 µg vaccination at months 1 and 6 after the full course of the vaccinations, respectively. The positive rate in CKD patients without immune suppression or hormone therapy was 3.33 (95%CI: 1.26-8.80) and 4.78 (95%CI: 1.47-15.57) times higher than those in the patients with such therapy, respectively. Conclusions:b> Four doses of 20 µg or 60 µg hepatitis B vaccination could improve the immunogenicity in patients with CKD. And four doses of 60 µg vaccination might play a positive role in maintaining anti-HBs in this population. The immunogenicity in the CKD patients with immune suppression or hormone therapy was poor.
Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Follow-Up Studies ; Hepatitis B/prevention & control* ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Humans ; Immunization, Secondary ; Renal Insufficiency, Chronic ; Vaccination

Chronic hepatitis B virus (HBV) infection is a serious health issue because of its severe sequelae. Prevention of mother-to-child transmission (MTCT) of HBV is critical to eliminate chronic HBV infection. Here, we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade. A universal hepatitis B vaccination program started from 2002 has been intensified, with the coverage of timely birth dose >95% of all newborn infants from 2012. Since 2011, China has taken a nationwide program to administer hepatitis B immunoglobulin (HBIG) with free of charge in all neonates of HBV-infected mothers, leading to a significant increment of timely use of HBIG. The prevalence of hepatitis B surface antigen (HBsAg) was declined from around 10% among children in 1980s to <0.5% among children born after 2011. Administration of oral antiviral agents in HBV-infected pregnant women with HBV DNA >2 × 105 U/mL during the third trimester is increasing, which will further reduce MTCT of HBV. However, there are some challenges in the elimination of HBV infection in children, which need to overcome by the concerted efforts. Nevertheless, it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged <5 years is ≤0.1% by 2030.
China/epidemiology* ; Female ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic/prevention & control* ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical/prevention & control* ; Pregnancy ; Pregnancy Complications, Infectious/epidemiology*

Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides "perfect strategies" to eliminate vertical transmission. However, there is still a notable gap between "perfect strategies" and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.
Female ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Pregnancy

The mother-to-child transmission(MTCT) of hepatitis B virus (HBV) is the dominant cause of chronic HBV infection. In order to achieve the goal of "zero" MTCT before pregnancy, during pregnancy, and after pregnancy; standardized management for hepatitis HBV infection in women of childbearing age should be regulated. The content of this consensus includes: screening and treatment of HBV in pregnant women and women of childbearing age, treatment of hepatitis B during pregnancy, preventive measures and evaluation of combined immunization of hepatitis B immunoglobulin and hepatitis B vaccine in newborns, anti-viral therapy for all pregnant women with a high HBV DNA level and post-partum period related management. In addition, 16 recommendations were formed for clinicians to standardize the clinical management of HBV infection in women of child-bearing age.
Child ; Consensus ; Female ; Hepatitis B/virology* ; Hepatitis B Vaccines/administration & dosage* ; Hepatitis B virus ; Hepatitis B, Chronic/prevention & control* ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/prevention & control* ; Pregnancy ; Pregnancy Complications, Infectious/prevention & control*

The recent outbreak of hepatitis C virus (HCV) at Singapore General Hospital (SGH) has highlighted the dangers of viral hepatitis. In this case, infection control and environmental contamination were the culprits, particularly, a drop of blood containing 5 million IU HCV. From a broader perspective, there has been a revolution in HCV therapy with the recent rapid evolution of short-term (12 weeks) safe, all oral directly- acting antiviral (DAA) therapy leading to cure rates of 90% to 100%, even in previously difficult to treat patients with liver cirrhosis, previous treatment failure and those on immunosuppression. Consequently, treating HCV in risk groups such as renal dialysis and haemophiliacs can eliminate a pool of infected patients to prevent future outbreaks. A seroprevalence study is needed to identify a possible "birth cohort" effect that could aid screening. For HBV, vaccination has reduced prevalence to 3.8%, but these patients are prone to complications such as HBV flares. Since 2014, 13 patients developed liver failure and were listed for liver transplantation at National University Hospital (NUH) but 6 died beforehand. This avoidable catastrophe is due to undiagnosed HBV infection or patients who did not return for follow-up. Good antiviral therapy is available, but the issues are similar to HCV, identification of patients and linkage to care. A cure seems likely in the future as pharmaceutical companies are developing new agents. Singapore has joined in this initiative with a recent award of a national research translational grant to better understand the pathophysiology and the processes needed for a cure of HBV.
Antiviral Agents ; therapeutic use ; Disease Outbreaks ; prevention & control ; Health Services Accessibility ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B, Chronic ; drug therapy ; epidemiology ; prevention & control ; Hepatitis C, Chronic ; drug therapy ; epidemiology ; Humans ; Patient Selection ; Risk Assessment ; Singapore ; epidemiology

<b>OBJECTIVEb>To evaluate the long-term protection efficacy of neonatal hepatitis B vaccination on chronic hepatitis B (CHB) and liver fibrosis and cirrhosis in adults.

<b>METHODSb>From January to October, 2013, a cross-sectional study was conducted among the participants from Qidong Hepatitis B Intervention Study (QHBIS), who were selected through stratified random sampling. The detections of serum alanine aminotransferase (ALT), HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe were conducted and ultrasonography on liver, gallbladder and spleen was performed for them. The positive rates of each serologic markers, the prevalence of active CHB and liver fibrosis and cirrhosis were calculated, the gender specific differences between vaccination group and control group were compared with Chi-square test.

<b>RESULTSb>A total of 4 421 participants aged (25.59±1.84) years in vaccination group and 3 880 participants aged (26.61±2.24) years in control group were surveyed. The positive rates of HBsAg, anti-HBs, anti-HBc, HBeAg and anti-HBe were 2.38%, 37.73%, 3.78%, 0.57% and 2.15% in vaccination group, and 9.02%, 29.41%, 16.83%, 2.73% and 8.87% in control group, respectively, the differences between two groups were statistically significant (all P<0.05). The prevalence of active CHB and liver fibrosis and cirrhosis were 0.45% and 0.16% in vaccination group, 1.29% and 0.39% in control group, the differences between two groups were statistically significant (P<0.05). The active CHB prevalence was lower in females than in males in both vaccination group and control group (P<0.05). The liver fibrosis and cirrhosis prevalence was lower in females than in males in control group (P<0.05); whereas, no statistical significant difference in liver fibrosis & cirrhosis prevalence between males and females was found in vaccination group (P>0.05).

<b>CONCLUSIONSb>Protection conferred by neonatal hepatitis B vaccination could last to marrying age. The gender specific difference in protection efficacy needs further study.

Adult ; China ; Cross-Sectional Studies ; Female ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Hepatitis B, Chronic ; prevention & control ; Humans ; Liver Cirrhosis ; Male ; Prevalence ; Vaccination ; statistics & numerical data

With recent advances in molecular and genomic investigations, the impact of hepatitis B viral and host factors on the progression of chronic HBV infection has been explored. For viral factors, hepatitis B viral load is a strong predictor for liver disease progression. Hepatitis B viral kinetics appear to be important for successful anti-viral therapy. Serum HBsAg level serves as a complementary marker to viral load for the prediction of HBV-related adverse outcomes in patients with low viral load. In those with low viral load, high serum HBsAg level is associated with higher risks of cirrhosis and HCC. Hepatitis B core-related antigen (HBcrAg) induces host immune responses, and the reduction of the HBcrAg level as well as the increment of total anti-HBc level are significantly associated with favorable outcomes. HBV genotypes (genotype C/D) and mutants (basal core promoter and deletion mutation in pre-S genes) are well known viral genetic markers to predict disease progression. For host factors, serum inflammatory biomarkers have been developed to evaluate the HBV-associated hepatic necroinflammation and fibrosis. Host single nucleotide polymorphism on sodium taurocholate cotransporting polypeptide (NTCP, an HBV entry receptor) may be associated with a decreased risk for cirrhosis and HCC. In conclusion, patients with chronic hepatitis B should be evaluated with relevant viral and host markers to identify those who are at a higher risk of liver disease progression and then receive timely antiviral therapy.
Biomarkers/*blood ; DNA, Viral/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/prevention & control ; Humans ; Liver Cirrhosis/etiology ; Organic Anion Transporters, Sodium-Dependent/genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Symporters/genetics

Recent studies suggest that liver cirrhosis is reversible after administering oral nucleos(t)ide analogue therapy to patients with hepatitis B virus (HBV) infection. However, few studies have addressed whether esophageal varices can regress after such therapy. We report a case of complete regression of esophageal varices during entecavir therapy in patients with HBV-related liver cirrhosis, suggesting that complications of liver cirrhosis such as esophageal varices can regress after the long-term suppression of HBV replication.
Abdomen/diagnostic imaging ; Antiviral Agents/*therapeutic use ; DNA, Viral/blood ; Esophageal and Gastric Varices/complications/prevention & control ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/*diagnosis/etiology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Ultrasonography

<b>OBJECTIVEb>To observe the clinical efficacy of combination therapy with peg-IFNalpha and adefovir (CPIA) in women who were hepatfis B virus (HBV) carriers and had just given birth and received telbivudine (LdT) during pregnancy for prevention of mother-to-child transmission.

<b>METHODSb>One-hundred-and-fifty third trimester-pregnant women who were HBV carriers with highly-viremic were treated with LdT until time of birth. After delivery, those women with alanine aminotransferase (ALT) level exceeding two times the upper limit of normal and HBV DNA level that had decreased more than 31 gIU/mL or hepatitis B e antigen (HBeAg) titer that had decreased more than 50% were switched to CPIA for 96 weeks.

<b>RESULTSb>Following delivery, 45 of the women were switched to the CPIA treatment, of which 91.1% (41/45) achieved virological response, 55.6% (25/45) achieved HBeAg clearance or seroconversion, and 26.7% (12/45) achieved hepatitis B surface antigen (HBsAg) clearance or seroconversion.The immediate post-delivery (and pre-CPIA) levels of HBeAg and HBV DNA were negatively associated with HBeAg clearance. Ninety-eight of the total study participants stopped the LdT treatment and there were no cases of significant deterioration of liver function.

<b>CONCLUSIONb>Pregnant women who are HBV carriers and receive LdT for protection against mother-to-child transmission, and who show significant ALT elevation and decreased HBeAg titer and/or reduced HBV DNA after delivery, may be good candidates for the CPIA therapy following delivery.

Adenine ; analogs & derivatives ; therapeutic use ; Alanine Transaminase ; blood ; Antiviral Agents ; therapeutic use ; Carrier State ; virology ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infectious Disease Transmission, Vertical ; prevention & control ; Interferon-alpha ; therapeutic use ; Organophosphonates ; therapeutic use ; Polyethylene Glycols ; therapeutic use ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; virology ; Pregnancy Trimester, Third ; Recombinant Proteins ; therapeutic use ; Thymidine ; analogs & derivatives ; therapeutic use

<b>OBJECTIVEb>To observe the long-term efficacy and safety of telbivudine (LdT) for pregnant women with chronic hepatitis B (CHB) and their children born from the treatment period.

<b>METHODSb>A total of 118 pregnant women with CHB were enrolled in the study and provided informed consent for participation. The women opted for participation in the treatment group (7 =73; LdT 600 mg once daily, starting in early pregnancy and continued until after delivery) or in the control group (n =45; no LdT treatment). All newborns were given active and passive immunization upon birth and tested for serum hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), anti-hepatitis B core antibody (anti-HBc), anti-hepatitis B surface antibody (anti-HBs) and HBV DNA at 0, 1, 7 and 12 months of age. The Paediatrics Neuropsychological Development Scale for Children aged 0 - 6 (5 items) established by the Capital Institute was used to test the children; in addition, the children were evaluated by observation for action ability (fine and gross motor skills), adaptability, language ability and social behaviour. Total IQ was estimated as a developmental quotient (DQ) by using the equation: points from the 5 scale items actual age in months * 100.

<b>RESULTSb>The LdT group included 69 women with successful pregnancies, 1 case of miscarriage and 3 cases that were lost to follow-up. The control group included 34 women with successful pregnancies, 4 cases of miscarriage, 1 case with fatal outcome, and 6 cases of no pregnancy. Compared to the control group, the LdT group had a significantly higher successful pregnancy rate (x² =4.86 in the LdT group, P < 0.05). In addition, the LdT group had a significantly higher rate of term delivery (53 cases vs. 34 cases, x² = 6.38, P < 0.05). The neonates born to the women in the LdT group included 53 cases of weakly-negative HBsAg at birth and 1 case at 1 month old, as well as negativity for HBV DNA, and HBsAg remaining weakly positive at 6 months old; the intrauterine infection rate was 1.8% and no case of deformity occurred.Among the 34 neonates in the control group, 6 showed HBsAg positivity at 1 month old, and the HBsAg positivity remained for all 6 at 6 months old; the intrauterine infection rate was 16.6%, which was significantly higher than that of the LdT group (x² = 5.10, P < 0.05). The neonates in the LdT group had a significantly higher anti-HBs production rate at 1 year old than those in the control group (98.1% (52/53 vs. 82.4% (28/34). X² = 4.87, P < 0.05). The neonates in the LdT group showed normal growth and development for all 53 cases of young children, and IQ levels of excellent for 3 cases, smart for 8 cases, normal for 40 cases, and low for 2 cases. The neonates in the control group showed normal growth and development for all 34 cases of young children, and IQ levels of excellent for 2 cases, smart for 4 cases, normal for 27 cases, and low for 1 case.

<b>CONCLUSIONb>Childbearing chronic HBV patients treated with LdT had higher rates of successful pregnancy, blocking of intrauterine infection and anti-HBs reduction compared to their untreated counterparts. The children bom to LdT-treated women showed no difference in long-term growth and development and total IQ from the children born to the untreated women with chronic HBV.

Adolescent ; Adult ; Antiviral Agents ; adverse effects ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Pregnancy Complications, Infectious ; drug therapy ; Thymidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Young Adult