Currently, Korea is a low endemicity country for HAV, especially in children. However, recent reports of hepatitis A outbreaks show that there has been a shift of disease incidence to adolescents and young adults, with 2 cases of acute liver failure in one reported outbreak. We need to study the immune status for HAV in order to provide information for the establishment of preventive measures and possible consequences of HAV in Korea. A total of 334 infants, children and adolescents less than 20 years of age living in rural areas of Kyonggi Province, Korea were evaluated for anti-HAV immune status in 1996. Five hundred and eighty-four primary school children living in the same area were separately evaluated for the natural seroconversion rate between 1993 and follow-up samples taken in 1996. Anti-HAV IgG antibody was measured by enzyme immunoassay (HAVAB EIA kit, Abbott Laboratories, Chicago, Illinois, USA). In comparison with previous reports of seroprevalence rates, our data confirmed a dramatic drop in seroprevalence rates among children and adolescents under 20 years of age living in rural areas, from over 63.8% two decades ago to 4.6% in 1996. Natural acquisition of HAV antibody in primary school children rarely occurs, registering only 0.5% during three years. Several outbreaks in young adults during 1996-1998 suggested that immunity against HAV in this population is so low that massive outbreaks are unavoidable. Teenagers and young adults, especially soldiers, who are likely to be exposed to contaminated food or water, would also have a greater risk of hepatitis A. Immunizing children with HAV vaccine as a routine schedule should also be considered in Korea in the future, particularly if the disease burden could be estimated and the cost-effectiveness of the vaccine could be proved.
Adolescence ; Adult ; Age Distribution ; Child ; Child, Preschool ; Female ; Hepatitis A/prevention & control* ; Hepatitis A/epidemiology* ; Hepatitis A Vaccines ; Human ; Immunization* ; Infant ; Korea ; Male ; Prevalence ; Sex Distribution ; Viral Hepatitis Vaccines/therapeutic use*

OBJECTIVETo evaluate the incidence of precore mutation in HBeAg negative HBV infected patients and the therapeutic effect of the immune therapy (levamisole + HBV vaccine + dipyridamole) on patients chronically infected by HBV with precore mutation.

METHODSThe precore region of HBV from the HBeAg (-) chronic hepatitis patients was sequenced and the patients suffered from HBV with precore mutation were treated with immune therapy.

RESULTSThe precore mutation rate was 10/12. The therapeutic effect of the immune therapy on the precore mutation patients (5/7) was better than that on the HBsAg(+), HBeAg(+) patients (2/11), P less than 0.05.

CONCLUSIONThe precore mutation rate was quite high in the HBsAg(+), HBeAg(-) patients we studied. The immune-therapy has some therapeutic effects on the patients with precore mutation. But the number of cases was too small, further study is needed.

Adolescent ; Adult ; Child ; Combined Modality Therapy ; DNA, Viral ; blood ; Dipyridamole ; therapeutic use ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; therapy ; virology ; Humans ; Immunotherapy ; Lamivudine ; therapeutic use ; Levamisole ; therapeutic use ; Middle Aged ; Mutation

Hepatitis, Viral, Human ; history ; prevention & control ; transmission ; History, 18th Century ; History, 20th Century ; History, Ancient ; Humans ; Viral Hepatitis Vaccines ; therapeutic use

OBJECTIVESTo establish a transplanted tumor producing HCV NS3 protein in mice and study the therapeutic effect of minigene vaccine based on invariant chain substitution.

METHODSSP2/0-NS3 cells expressing HCV NS3 antigen were injected subcutaneously into BALB/ c mice. After three days of inoculation, different therapeutical reagents were injected intramuscularly into different groups of mice. The boost immunization was carried out two weeks after the first immunization. The efficiency of HCV NS3 Th1 minigene vaccine was estimated after 60 days observation.

RESULTSFor saline, pCI-neo, pHCV-NS3 and pHCV-NS3-Th1 treated groups, the induction period needed for tumor growth was 16.17+/-2.55, 14.40+/-1.82, 16.75+/-2.36, and 24.00+/-5.57 days (t =2.623, P =0.034 vs saline, t =3.713, P =0.010 vs pCI-neo and t =2.425, P =0.045 vs pHCV-NS3) respectively. The tumorigenesis rates were 100%, 100%, 57.1% (8/14, chi2 = 6.190, P = 0.013 vs saline and chi2 = 6.608, P = 0.010 vs pCI-neo) and 46.7% (7/15, chi2 = 9.707, P = 0.002 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo ) respectively. The survival rates were 0, 0, 50.0% (7/14, chi2 = 5.787, P = 0.016 vs saline and chi2 = 9.333, P = 0.002 vs pCI-neo) and 53.3% (8/15, chi2 = 6.651, P = 0.010 vs saline and chi2 = 10.311, P = 0.001 vs pCI-neo) respectively. The average tumor diameter of the pHCV-NS3-Th1 treated group was significantly smaller compared with the control groups and the pHCV-NS3 treated group (P =0.001). Moreover, the average survival time of tumor-bearing mice immunized with pHCV-NS3-Th1 was 6 days longer compared with the saline treated group, 12 days longer compared with the pCI-neo treated group (P =0.001), and 6 days compared with the pHCV-NS3 treated group.

CONCLUSIONHCV NS3 Th1 epitope vaccine might be a potential biotherapy candidate against HCV infection.

Animals ; Female ; Mice ; Mice, Inbred BALB C ; Multiple Myeloma ; metabolism ; pathology ; Neoplasm Transplantation ; Random Allocation ; Tumor Cells, Cultured ; Vaccines, Synthetic ; therapeutic use ; Viral Hepatitis Vaccines ; therapeutic use ; Viral Nonstructural Proteins ; biosynthesis ; genetics

Aim: To identify the key risk factors of intrauterine hepatitis B virus transmission (HBV) and its effect on the placenta and fetus. Methods: 425 infants born to hepatitis B surface antigen (HBsAg)-positive pregnant women who received combined immunization with hepatitis B immunoglobulin and hepatitis B vaccine between 2009 to 2015 were prospectively enrolled in this study. The intrauterine transmission situation was assessed by dynamic monitoring of infants HBV DNA load and quantitative HBsAg. Univariate and multivariate regression analysis was used to determine the high risk factors for intrauterine transmission. Stratified analysis was used to determine the relationship between maternal HBV DNA load and fetal distress. Transmission electron microscopy was used to observe HBV Effects on placental tissue. Results: HBV intrauterine infection rate was 2.6% (11/425). Multivariate analysis result showed that the maternal HBV DNA load was an independent risk factor for intrauterine infection among infants (P=0.011). Intrauterine infection and distress rate was significantly higher in infants with with maternal HBV DNA>10⁶ IU/ml than those with HBV DNA <10⁶ IU/ml (12.2% vs. 1.8%; χ²=11.275, P=0.006), and (24.4% vs. 16.0%, χ²=3.993, P=0.046). Transmission electron microscopy showed that mitochondrial edema, endoplasmic reticulum expansion and thicker basement membrane were apparent when the maternal HBV DNA>10⁶ IU/ml than that of maternal HBV DNA<10⁶ IU/ml (960 nm vs. 214 nm, Z=-2.782, P=0.005) in the placental tissue. Conclusion: Maternal HBV DNA>10⁶ IU/ml is associated not only with intrauterine infection, but also with increased incidence of intrauterine distress and placental sub-microstructural changes, providing strong clinical and histological evidence for pregnancy avoidance and treatment in this population.
DNA, Viral ; Female ; Fetal Distress/drug therapy* ; Hepatitis B/prevention & control* ; Hepatitis B Surface Antigens ; Hepatitis B Vaccines/therapeutic use* ; Hepatitis B virus/genetics* ; Humans ; Immunoglobulins/therapeutic use* ; Infant ; Infectious Disease Transmission, Vertical/prevention & control* ; Placenta ; Pregnancy ; Pregnancy Complications, Infectious

OBJECTIVETo observe the efficacy of treating intrauterine infected chronic hepatitis B virus (HBV) carrier children with a combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) or hepatitis B immunoglobulin (HBIG) plus recombinant hepatitis B vaccine (rHBvac).

METHODSA total of 27 chronic HBV infected children, who were born to HBV carrier mothers and received hepatitis B immunoprophylaxis at birth, were randomized into 2 groups: one receiving a combined therapy of 50 micro g of GM-CSF plus 10 micro g of rHBvac injected intramuscularly at the same location (GM-CSF group, 14 children) or 200 IU HBIG and 10 micro g rHBvac in different muscles (HBIG group, 13 children) on a monthly four-dose schedule. HBV-DNA quantification and other HBV serological markers were tested before and after the four-dose therapy.

RESULTSTwelve children in each group completed the study. Of them, 3 children in the GM-CSF group and 4 in the HBIG group had elevated serum alanine transaminase (ALT) before the trial, and then 2 in each group became ALT normal after the treatment. Before the therapy, hepatitis B e antigen (HBeAg) positivity was found in nine children in the GM-CSF group and 10 in the HBIG group. One from each group had an HBeAg/anti-HBe seroconversion after the treatment. The quantity of HBV-DNA was significantly lower after the treatment (P = 0.023) in GM-CSF group, but was not significantly reduced in HBIG group. No subjects were found to be negative for hepatitis B surface antigen (HBsAg) after the treatment, and no serious adverse events occurred in either group.

CONCLUSIONCombined GM-CSF and rHBvac therapy inhibit HBV replication in carrier children who were not protected after treatment with immunoprophylaxis.

Carrier State ; therapy ; Child ; Child, Preschool ; Combined Modality Therapy ; DNA, Viral ; blood ; Granulocyte-Macrophage Colony-Stimulating Factor ; therapeutic use ; Hepatitis B Vaccines ; immunology ; Hepatitis B, Chronic ; therapy ; Humans ; Immunoglobulins ; therapeutic use ; Pilot Projects ; Vaccines, Synthetic ; immunology

Carbamates ; therapeutic use ; Hepatitis C ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Interferons ; therapeutic use ; Macrocyclic Compounds ; Oligonucleotides, Antisense ; therapeutic use ; Quinolines ; RNA Replicase ; antagonists & inhibitors ; Serum Albumin ; therapeutic use ; Serum Albumin, Human ; Thiazoles ; therapeutic use ; Viral Hepatitis Vaccines ; therapeutic use

OBJECTIVETo conduct a prospective randomized controlled trial of infants born to hepatitis B virus (HBV) surface antigen (HBsAg)-positive mothers in order to investigate the dynamic changes in the titer of anti-HBV surface protein (HBS) induced by treatment with combined immunoprophylaxis (200 IU hepatitis B immunoglobulin (HBIG) and 5 or 10 mug yeast recombinant hepatitis B vaccine), to compare the protective effect of 5 and 10 mug hepatitis B vaccine, and to provide an immunization strategy, monitoring mode and booster immunization schedule for the high-risk group.

METHODSTwo-hundred-and-sixty-nine infants born to HBsAg positive mothers were given combined immunoprophylaxis at birth, and the venous blood samples (at birth, and 1, 7 and 12 months) were tested for HBV DNA load, and HBsAg and anti-HBS titers.

RESULTSThe overall 1-year protective rate of combined immunoprophylaxis was 95.9%. There was no significant difference between the infectious rates of infants given the 5 mug or the 10 mug hepatitis B vaccine (x2 = 0.876, P = 0.377). The geometric mean titers (GMTs) of anti-HBS were 144.1 mIU/ml at 1-month old and 564.9 mIU/ml at the age of 7 months old (the highest point), but declined to 397.6 mIU/ml at the age of 12 months old. The rate of infants with anti-HBS titer less than 100 mIU/ml was 20.9%, and that of less than 10 mIU/ml was 7.4% at 7-month-old; the rate of infants with anti-HBS titer less than 100 mIU/ml increased to 30.2% and that of less than 10 mIU/ml increased to 15.9% at 12-month-old. At 7-month-old, the GMT of the 10 mug vaccine group was higher than that of the 5 mug vaccine group (675.3 mIU/ml vs. 25.0 mIU/ml, P = 0.001) and the rate of infants with anti-HBS titer less than 10 mIU/ml was significantly lower in the 10 mug vaccine group (2.3% vs. 12.6%, P = 0.002); at 12-month-old, the rate of infants with anti-HBS titer less than 100 mIU/ml was also significantly lower in the 10 mug group (20.6% vs. 40.2%, P = 0.001).

CONCLUSIONCombined immunoprophylaxis is therapeutically efficacious for treating infants born to HBsAg positive mothers. Monitoring these infants' anti-HBs titer will help to identify non- or low-responders in a timely manner. The high-dose hepatitis B vaccine is preferable to the low-dose, and should be considered for use in immunization strategies for these infants.

Female ; Hepatitis B ; blood ; immunology ; prevention & control ; Hepatitis B Antibodies ; blood ; immunology ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B Vaccines ; therapeutic use ; Humans ; Infant ; Mothers ; Prospective Studies ; Viral Load

OBJECTIVETo evaluate the advantages of combination therapy with interferon-alpha plus nucleoside analogue-lamivudine or HBV vaccine in children with HBeAg positive chronic hepatitis B.

METHODSA total of 120 patients with HBeAg positive chronic hepatitis B were divided into three groups, 40 patients per group. Each group was treated with one of the following therapies respectively: Group A IFN-alpha 1b 10 MU/m2 three times per week (Tiw); Group B IFN-alpha 1b 10MU/m2 three times per week (Tiw) plus lamivudine 3 mg/kg for 6 months. Group C IFN-alpha 1b 10 MU/m2 three times per week (Tiw) plus HBV vaccine 30 microg one a month.

RESULTSThere was no significant difference in normalizing rate of ALT among the three groups at end of treatment. There was more significant difference in negative rate (seroconversion) of serum HBV DNA and HBeAg in group B than group A and group C (P less than 0.05).

CONCLUSIONThe combination therapy of IFN-alpha 1b plus lamivudine seemed to be more effective than the therapy with IFN-alpha alone and the combination of IFN-alpha and HBV vaccine.

Anti-HIV Agents ; therapeutic use ; Child ; Child, Preschool ; DNA, Viral ; blood ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B e Antigens ; blood ; genetics ; immunology ; Hepatitis B virus ; drug effects ; genetics ; immunology ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; therapeutic use ; Lamivudine ; therapeutic use ; Male ; Treatment Outcome

OBJECTIVETo explore the factors influencing failure of an immunization to interrupt perinatal (mother-to-child) transmission of hepatitis B virus (HBV).

METHODSBetween June 2006 and March 2010, a total of 1355 pregnant women testing positive for the hepatitis B surface antigen (HBsAg), at gestational weeks 20 to 42, and without use of antiviral or immunomodulatory drugs during the pregnancy were prospectively recruited to the study. The mothers were given a choice of receiving hepatitis B immunoglobulin (HBIG; three 200 IU intramuscular injections give at four-week intervals starting from gestation week 28) or not. All neonates (1360, including five sets of twins) received hepatitis B vaccine (10 mug) plus HBIG (200 IU) combined immunization within 24 h of birth, as early as possible. Peripheral venous blood samples were collected from the neonates within 24 h of birth and at 7 and 12 months of age for detection of HBV markers, including hepatitis B e antigen (HBeAg) and HBV DNA. The infants were classified according to HBV perinatal transmission status (infection group and non-infection group) and various factors (maternal-related: age, gravidity, parity; pregnancy/birth-related: threatened premature labor, complications; neonate-related: sex, birth weight, apgar score) were compared between the two groups by using non-conditional logistic regression analysis to determine their potential influence on failure of immunization to inhibit transmission.

RESULTSAfter 12 months of follow-up, 1.54% (21/1360) of the neonates had presented with HBV infection. Analysis of the HBV-infected neonates revealed differences in infection rates between neonates born to mothers with HBIG injection (2.22% vs. without HBIG injection: 1.11%, P less than 0.05) and caesarean section (1.35% vs. vaginal delivery: 1.73%) but neither reached statistical significance (P less than 0.05); only the practice of breastfeeding showed a significant difference for infection rate, with neonates fed artificial formula having higher infection rate (3.13%) than the breastfed neonates (0.27%, P less than 0.05). The neonate HBV infection rate was also significantly higher for neonates born to HBeAg-positive mothers (4.44% vs. HBeAg-negative mothers: 0%, P less than 0.05) and HBV DNA-positive mothers (3.13% vs. HBV DNA-negative mothers: 0%, P less than 0.05). When the mothers were stratified by serum level of HBV DNA, there was a significant difference in HBV-infected neonates born to mothers with more than or equal to 1*10(7) IU/ml(6.01% vs. 10(3)-10(6) IU/ml: 0.56% and less than 1*10(3) IU/ml: 0%, both P less than 0.05). Logistic regression analysis indicated that the independent risk factors for HBV perinatal transmission despite immunization were maternal serum HBeAg-positive status (relative risk (RR)=31.74, 95% confidence interval (CI): 3.88-259.38) and maternal HBV DNA of ≥ 10⁷ copies/mL (RR=22.58, 95% CI: 4.75-107.40).

CONCLUSIONFailure of vaccine plus HBIG to interrupt mother-to-child transmission of HBV is influenced by maternal serum HBeAg-positive status and maternal HBV DNA of ≥10⁷ copies/mL.

Adult ; DNA, Viral ; blood ; Female ; Hepatitis B ; prevention & control ; transmission ; virology ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; therapeutic use ; Hepatitis B virus ; Humans ; Immunoglobulins ; therapeutic use ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; prevention & control ; Pregnancy ; Pregnancy Complications, Infectious ; prevention & control ; virology ; Pregnancy Trimester, Second ; Pregnancy Trimester, Third ; Prospective Studies ; Risk Factors ; Viral Load