First line nucleos(t)ide analog monotherapy is more cost-effective than combination strategies in hepatitis B e antigen-positive chronic hepatitis B patients in China.

BACKGROUND: Nucleos(t)ide analog (NA) in combination with peginterferon (PegIFN) therapy in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) shows better effectiveness than NA monotherapy in hepatitis B surface antigen loss, termed "functional cure," based on previous published studies. However, it is not known which strategy is more cost-effective on functional cure. The aim of this study was to analyze the cost-effectiveness of first-line monotherapies and combination strategies in HBeAg-positive CHB patients in China from a social perspective. METHODS: A Markov model was developed with functional cure and other five states including CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and death to assess the cost-effectiveness of seven representative treatment strategies. Entecavir (ETV) monotherapy and tenofovir disoproxil fumarate (TDF) monotherapy served as comparators, respectively. RESULTS: In the two base-case analysis, compared with ETV, ETV generated the highest costs with $44,210 and the highest quality-adjusted life-years (QALYs) with 16.78 years. Compared with TDF, treating CHB patients with ETV and NA - PegIFN strategies increased costs by $7639 and $6129, respectively, gaining incremental QALYs by 2.20 years and 1.66 years, respectively. The incremental cost-effectiveness ratios were $3472/QALY and $3692/QALY, respectively, which were less than one-time gross domestic product per capita. One-way sensitivity analysis and probabilistic sensitivity analyses showed the robustness of the results. CONCLUSION: Among seven treatment strategies, first-line NA monotherapy may be more cost-effective than combination strategies in HBeAg-positive CHB patients in China.

MicroRNA-155 inversely correlates with esophageal cancer progression through regulating tumor-associated macrophage FGF2 expression.

Esophageal cancer (EC) is one of the most common malignancies with high incidence and mortality. Tumor-associated macrophages (TAMs) in the tumor microenvironment have been linked to the accelerated tumor progression. MicroRNAs (miR) are 19-25 nucleotide-long, noncoding RNA molecules, functioning as modulators of gene expression, and mediate a variety of biological functions, including tumor growth. In the present study, the effects and molecular mechanism of miR-155 in TAMs isolated from EC were explored. The expression of miR-155 and fibroblast growth factor-2 (FGF2) in EC tissues and cell lines were analyzed using reverse transcription-quantitative PCR (qRT-PCR) and western blot assays. TAMs were also transfected with the described constructs. Following, the culture medium from TAMs was collected for further analysis. The released FGF2, and inflammatory cytokines were quantified using ELISA. The cell viability, migrated and invaded levels were calculated through Cell Counting kit-8 (CCK8), and transwell analysis. Moreover, human umbilical vein endothelial cells (HUVEC) vasculature formation was determined using matrigel angiogenesis analysis. The results indicated that miR-155 expression was decreased in EC tissues and cell lines, while FGF2 expression was increased in comparison to those in the normal control group. Moreover, miR-155 mimics transfection up-regulated tumor necrosis factor α (TNF-α), interleukin (IL)-12 and inducible nitric oxide synthase (iNOS), while down-regulated IL-10, Arginase-1 (Arg-1) and IL-22 levels in the culture medium from TAMs. And enhancing miR-155 expression in TAMs suppressed the cell viability, migration and invasion of ECA109 cells and reduced the angiogenesis. Nevertheless, over-expressing FGF2 abolished the role of miR-155 in cancer cell survival, migration, invasion as well as angiogenesis. Our findings indicated that miR-155-regulated FGF2 expression from TAMs suppressed EC cell proliferation, migration, invasion and inhibited vasculature formation. Thus, miR-155-modulated FGF2 might be a potential therapeutic target to prevent EC progression.

Quantitative study of iron metabolism-related genes expression in rat.

OBJECTIVE: To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues. METHODS: Two groups (n=30) of Sprague-Dawley female weanling rats were fed with a control diet and an iron deficient diet respectively for 4 weeks. All rats were then sacrificed, and blood and tissue samples were collected. The routine blood examination was performed with a veterinary automatic blood cell analyzer. Elemental iron levels in liver, spleen and serum were determined by atomic absorption spectrophotometry. The mRNA expression of genes was detected by real-time fluorescence quantitative PCR. RESULTS: After 4 weeks, the hemoglobin (Hb) level and red blood cell (RBC) count were significantly lower in the iron deficient group compared with those in the control group. The iron levels in liver, spleen and serum in the iron deficient group were significantly lower than those in the control group. In reference to small intestine, the relative expression of each iron-related gene varied in the different tissues. Under the iron deficiency, the expression of these genes changed in a tissue-specific manner. The expression of most of the genes significantly correlated in intestine, spleen and lung, but few correlated in liver, heart and kidney. CONCLUSION: Findings from our study provides new understandings about the relative expression, regulation by iron and correlation among the mRNA expressions of transferrin receptors 1 and 2, divalent metal transporter 1, ferritin, iron regulation proteins 1 and 2, hereditary hemochromatosis protein, hepcidin, ferroportin 1 and hephaestin in intestine, liver, spleen, kidney, heart, and lung of rat.

Psychometrics of chronic liver disease questionnaire in Chinese chronic hepatitis B patients.

AIM: To evaluate psychometrics of the Chinese (mainland) chronic liver disease questionnaire (CLDQ) in patients with chronic hepatitis B (CHB). METHODS: A cross-sectional sample of 460 Chinese patients with CHB was selected from the Outpatient Department of the Eighth Hospital of Xi'an, including CHB (CHB without cirrhosis) (n = 323) and CHB-related cirrhosis (n = 137). The psychometrics includes reliability, validity and sensitivity. Internal consistency reliability was measured using Cronbach's α. Convergent and discriminant validity was evaluated by item-scale correlation. Factorial validity was explored by principal component analysis with varimax rotation. Sensitivity was assessed using Cohen's effect size (ES), and independent sample t test between CHB and CHB-related cirrhosis groups and between alanine aminotransferase (ALT) normal and abnormal groups after stratifying the disease (CHB and CHB-related cirrhosis). RESULTS: Internal consistency reliability of the CLDQ was 0.83 (range: 0.65-0.90). Most of the hypothesized item-scale correlations were 0.40 or over, and all of such hypothesized correlations were higher than the alternative ones, indicating satisfactory convergent and discriminant validity. Six factors were extracted after varimax rotation from the 29 items of CLDQ. The eligible Cohen's ES with statistically significant independent sample t test was found in the overall CLDQ and abdominal, systematic, activity scales (CHB vs CHB-related cirrhosis), and in the overall CLDQ and abdominal scale in the stratification of patients with CHB (ALT normal vs abnormal). CONCLUSION: The CLDQ has acceptable reliability, validity and sensitivity in Chinese (mainland) patients with CHB.

[Cost-utility analysis on universal childhood hepatitis A vaccination in regions with different anti-HAV prevalence rates of China].

OBJECTIVE: To explore the inputs and outputs of areas with different anti-HAV prevalence rates on universal childhood vaccination, and to provide a scientific basis for the formulation of the immunization strategy. METHODS: Since hepatitis A vaccination was scheduled at 12 and 18 months of age for all the healthy children, a single cohort including 1 000 000 individuals was formed in 2009, using the Chinese inactivated vaccine. Decision analysis was used to build Markov-decision tree model. The universal childhood hepatitis A vaccination was compared with non-vaccination group to evaluate the number of symptomatic infection, hospitalization, death, quality-adjusted life years (QALYs) lost, and the incremental cost-utility from the health system and the societal perspectives. Outcomes of the vaccination for the next 70 years were also predicted. The process of analysis was run separately in five regions defined by the anti-HAV prevalence rates (around 50%, 50% - 69%, 70% - 79%, 80% - 89% and > 90%). Sensitivity analysis was performed to test the stability or reliability of the results, and to identify sensitive variables. RESULTS: The study projected that, in the lowest, lower, and intermediate infection regions, the cost and output indicators of universal childhood hepatitis A vaccination were all lower than non-vaccinated group. Universal vaccination could gain QALYs and save both costs from the health system or the society. In the regions with higher infection rate, the output indicators of universal childhood hepatitis A vaccination were lower than in those non-vaccinated groups, except for the number of death due to hepatitis A, which had a 20 cases of increase. The model also predicted that in the highest infected region, universal vaccination would increase 4 560 814 and 5 840 430 RMB Yuan in the total costs from both the health system and the societies, respectively, when compared to the non-vaccination groups. Universal vaccination would also decrease the numbers of symptomatic infection, hospitalization, and QALYs lost, but would increase 51 deaths due to hepatitis A, and 1507, 1929 more RMB Yuan for each QALY gained from the health system and societal respectively, in the regions with highest infection rate. Sensitivity analyses discovered that the infection rate among those susceptible population and the proportion of those who initially under protection but subsequently lost their immunity every year, were the two main sensitive variables in the model. CONCLUSION: Our research discovered that the universal vaccination strategy should be based on the protective period of the vaccine and the anti-HAV prevalence in different endemic areas.

Comparison of long-term immunogenicity (23 years) of 10 µg and 20 µg doses of hepatitis B vaccine in healthy children.

To compare the long-term immunogenicity and seroprotection rates in healthy children following 23 years of vaccination with 10 µg or 20 µg doses of plasma-derived hepatitis B vaccine, we revisited all participants from our previous randomized controlled trial. At year 23, 81 participants were tested for HBV serological markers and HBV-DNA, and a booster dose was given to those with anti-HBs titer < 10 mIU/mL. After eliminating the interference of a Year 11 booster dose and vaccines received outside of the trial, around 50% of participants still maintained anti-HBs titers ≥ 10 mIU/mL in both 10 µg and 20 µg groups (p > 0.05). The peak immune response of vaccination (anti-HBs antibody levels at 12 mo after 1st vaccine dose) and Year 11 anti-HBs levels were significantly associated with Year 23 seroprotection rates. Most of the participants in both groups, regardless of their prior immune status, developed a rapid and robust anamnestic antibody response after the booster dose at year 23. No case of clinically significant HBV infection was observed during the entire study period of 23 y with only one transient HBsAg seroconversion in 10 µg vaccine group. We concluded that seroprotection provided by 10µg or 20 µg doses of hepatitis B vaccine persists for 23 years in more than half of vaccinated individuals in highly HBV-endemic areas, irrespective of 10 µg or 20 µg vaccine doses. Future studies with larger sample sizes comparing long-term efficacy of various doses of plasma-derived and recombinant HBV vaccines are recommended.

Ferroportin 1 and hephaestin expression in BeWo cell line with different iron treatment.

The process of placental iron transfer is an important physiological process during pregnancy. However, the molecular mechanism of placental iron transport has not been completely elucidated until now. Ferroportin 1 (FPN1) and hephaestin (Heph) have been identified as the important molecules involved in duodenal iron export. However, whether they participate in the placental iron efflux has been undefined until now. In this study, the BeWo cells were treated with desferrioxamine and Holo-transferrin human in different concentrations and harvested at 48 and 72 h. The mRNA expression of FPN1 and Heph was detected with quantitative real-time polymerase chain reaction, and the protein expression was detected with western blots. The results showed an up-regulated FPN1 expression with desferrioxamine treatment and down-regulated expression with Holo-transferrin human supplementation. However, the change of FPN1 expression at protein level was limited. Heph expression enhanced when cells were treated with desferrioxamine although the quantity of Heph expression was low. Heph expression showed no significant change with Holo-transferrin human supplementation. It indicates that FPN1 may participate in placental iron transport, and placental FPN1 expression is obviously not dependent on the iron regular element/iron regular protein regulation. An alternatively spliced FPN1 isoform that lacks an iron regular element may be the predominant expression in BeWo cells. It also demonstrates that Heph is active in placenta but may not play a key role in placental iron transport because it is not the main part of placental copper oxidase.

Divalent metal transporter 1 expression and regulation in human placenta.

Divalent metal transporter 1 (DMT1) is likely responsible for the release of iron from endosomes to the cytoplasm in placental syncytiotrophoblasts (STB). To determine the localization and the regulation of DMT1 expression by iron directly in placenta, the expression of DMT1 in human term placental tissues and BeWo cells (human placental choriocarcinoma cell line) was detected and the change in expression in response to different iron treatments on BeWo cells was observed. DMT1 was shown to be most prominent near the maternal side in human term placenta and predominantly in the cytoplasm of BeWo cells. BeWo cells were treated with desferrioxamine (DFO) and human holotransferrin (hTf-2Fe) and it was found that both DMT1 mRNA and protein increased significantly with DFO treatment and decreased with hTf-2Fe treatment. Further, DMT1 mRNA responded more significantly to treatments if it possessed an iron-responsive element than mRNA without this element. This study indicated that DMT1 is likely involved in endosomal iron transport in placental STB and placental DMT1 + IRE expression was primarily regulated by the IRE/IRP mechanism.

Antibody levels and immune memory 23 years after primary plasma-derived hepatitis B vaccination: results of a randomized placebo-controlled trial cohort from China where endemicity is high.

The duration of protection of hepatitis B vaccine remains incompletely understood. To assess the long-term protection provided by a primary vaccine series, the current study again recruited all subjects of a previous randomized placebo-controlled trial cohort 23 years after vaccination. Two hundred and sixty-one healthy children aged 5-9 years living in a highly HBV-endemic country were enrolled in the primary trial and received three doses of plasma-derived vaccine or placebo. The primary placebo receivers who did not receive any immunization against hepatitis B were used as non-vaccinated controls in the current study. After eliminating the interference of an early booster dose and vaccines outside the study, 48.1% (39/81) vaccinees still maintained anti-HBs titers ≥ 10 mI U/mL at Year 23, higher than 34.7% (26/75) in non-vaccinated controls (P=0.088). 75-100% of vaccinees with anti-HBs titer <10 mI U/mL at Year 23 in different sub-groups divided according to early immune backgrounds developed a rapid and robust antibody anamnestic response after a booster dose, highly significantly different from non-vaccinated controls who received the same dose of vaccine (7.5%, P<0.01). No case of clinically significant HBV infection was found in the primary cohort during the whole 23 years, but 10 transient HBsAg seroconversions in the primary placebo group and one in the primary vaccine group were determined. Anti-HBc positive rate obviously tended to be lower in vaccinees compared with non-vaccinated controls at Year 23. These results suggest a persisting immune memory and certain protection for 23 years after primary vaccination in children living in highly HBV-endemic areas. Clinically insignificant infections, which cannot be avoided and may often occur in vaccinees, play a positive role in the maintaining of immunity to HBV. Booster doses should be unnecessary for more than 20 years after a full primary immunization in children (as catch-up vaccination) and, also likely, in newborns living in highly HBV-endemic areas.

Analysis of correlation between blood biochemical indicators and bone mineral density of post-menopausal women.

Osteoporosis is a degenerative disease of the skeletal system, and its major complication is fracture that severely influences the living quality of the middle-aged and the aged. The purpose of this study was to investigate the significance of sex hormones and some biochemical indicators related to bone metabolism in the genesis and development of osteoporosis. The plasma samples were collected from 244 post-menopausal women of Xi'an urban area, and their plasma contents of testosterone, estradiol, calcitonin, osteocalcin and N-terminal propeptide of type I procollagen were detected by ELISA. The activity of tartrate-resistant acid phosphatase was determined by spectrophotometric method, and the content of nitric oxide was measured by Griess method. Bone mineral density (BMD) in lumbar vertebrae (L1-L4) and hips was measured by QDR-2000 dual energy X-ray absorptiometry. The concentrations of the biochemical indicators were compared among the three groups (normal bone mass group, osteopenia group and osteoporosis group), and Pearson correlation analysis was used to verify the correlations between the indicators and BMD. The comparison results of blood biochemical indicators of BMD-based groups showed that the plasma contents of estradiol (P = 0.006), testosterone (P = 0.038) and calcitonin (P = 0.042) decreased more significantly in the osteoporosis group, but the content of osteocalcin (P = 0.008) increased significantly in osteoporosis group than those in the other groups. The correlation analysis between BMD of different parts and the blood biochemical indicators showed that there was a significant positive correlation between estradiol and the BMD of lumber vertebra (r = 0.200, P = 0.002), femoral neck (r = 0.160, P = 0.013), and great trochanter (r = 0.204, P = 0.001). Significant positive correlations between calcitonin and BMD of lumber vertebra (r = 0.166, P = 0.018) and femoral great trochanter (r = 0.152, P = 0.041), and between testosterone and BMD of femoral great trochanter (r = 0.158, P = 0.014) were also observed. In addition, there existed significant negative correlations between osteocalcin and BMD of lumber vertebra (r = -0.220, P = 0.001), femoral neck (r = -0.259, P < 0.000), and great trochanter (r = -0.221, P = 0.001), and between the activity of tartrate-resistant acid phosphatase and BMD of femoral great trochanter (r = -0.135, P = 0.037). The partial correlation analysis also showed that there were significant correlations between estradiol (r = 0.160, P = 0.014), calcitonin (r = 0.240, P = 0.013), osteocalcin (r = -0.226, P = 0.023) and BMD when the influence of age was excluded. The Pearson correlation analysis of biochemical indicators showed there were positive correlations between the contents of testosterone and calcitonin, testosterone and osteocalcin, calcitonin and osteocalcin, calcitonin and PINP, calcitonin and NO, osteocalcin and NO, and PINP and NO, but negative correlations between the contents of testosterone and PINP, estradiol and calcitonin, estradiol and osteocalcin, and estradiol and NO. The blood contents of sex hormones and calcitonin significantly influence BMD and osteoporosis development, and the increase of osteocalcin contents could be used as a biomarker to indicate the degree of osteoporosis in post-menopausal women.

[Effect of plasma-derived hepatitis B vaccine 23(rd) year after a full course of vaccination in healthy young children].

OBJECTIVE: The aim of the study was to evaluate the anti-HBs persistence and the long term preventive efficacy after vaccination 23 years with plasma-derived hepatitis B vaccine. METHODS: The study consisted of 261 children who were 5 - 9 years aged, from two primary schools in two townships of Xi'an. 126 children were randomly selected as vaccine group, and 135 children in control group. These children were followed up again in 2009. Excluding self-inoculation, the vaccine and control groups were 81 and 75, who was used to ask to recall details of their experience for vaccination and liver-related illnesses during past twelve years. Individuals who had anti-HBs titers less 10 mIU/ml, HBsAg, anti-HBc and HBV-DNA all were negative, were given a booster dose vaccine and retest for anti-HBs titer after one month. RESULTS: After eliminated the interference of an early booster dose and vaccination outside the study, the positive rate of anti-HBs was 48.1% (39/81) in the vaccine group at year 23, higher than 34.7% (26/75) in control group. At year 23 after primary vaccination, 84.0% (21/25) individuals in the vaccine group whose anti-HBs and anti-HBc both are negative showed a stronger anamnestic response after received a booster dose, while 7.5% (3/40) in the control group. At year 23 after primary vaccination, none clinical case of hepatitis B was found among 194 individuals. However, anti-HBc positive rate in the vaccine group was 16.0% (13/81), while the rate in the control group was 30.7% (23/75) (χ(2) = 4.687, P < 0.05). CONCLUSION: At 23 years after implemented a full course of plasma-derived hepatitis B vaccine, the recipients of vaccine were maintained anti-HBs at a high level or strong immunological memory.

Correlation analysis between bone mineral density and serum element contents of postmenopausal women in Xi'an urban area.

The objective of this paper is to investigate the correlation between serum macro-element and trace element contents and bone mineral density (BMD) as well as the occurrence of osteoporosis. After the epidemiological investigation of 290 postmenopausal women from ages 45 to 65 in the Xi'an urban area, their blood was collected and serum concentrations of macro-elements, calcium, phosphonium, potassium, sodium, magnesium, and trace elements, zinc, iron, copper, and selenium were determined using atomic absorption spectrometry. Their BMD was measured by QDR-2000 dual-energy X-ray absorptiometry (DEXA). The correlation analysis between BMD and serum element contents was done with the software of SPSS 13.0. The correlation analysis of serum elements of postmenopausal women showed that there was a significant correlation between serum calcium and the other elements, and also a significant correlation between serum phosphonium and the others except serum potassium. The serum potassium content had a significant correlation with serum calcium, sodium and iron, but sodium content showed a significant correlation with the others except iron and selenium. In addition, copper had a significant correlation with the others except potassium and selenium. In correlation analysis between BMD and the elements contents, only did the potassium content show a significant positive correlation with BMD of lumbar vertebra and proximal femora. The comparison results between osteoporosis group, osteopenia group, and healthy group showed that there was no significant difference in the element contents between the groups, but there existed a tendency that potassium content increased with the rise of BMD. There exist significant correlations between the contents of serum elements such as calcium, phosphonium, sodium, potassium, magnesium, zinc, iron, copper, and selenium, but no significant differences in these elements contents between the osteoporosis group, osteopenia group, and healthy group. Serum potassium content shows a significant positive correlation with BMD, suggesting potassium may be involved in the development of osteoporosis in postmenopausal women.

A cost-effectiveness analysis of universal childhood hepatitis A vaccination in China.

The socioeconomic improvement has impacted hepatitis A virus (HAV) infection with a shift from high to intermediate endemicity in many parts of China. The first China-developed inactivated hepatitis A vaccine, with significantly low price, was licensed in 2002, prompting us to evaluate whether universal childhood vaccination is advisable now in China. We considered vaccination scheduled at ages 12 and 18 months for all healthy children, and assumed that a single cohort was enrolled in 2005. A Markov model was used to predict hepatitis A outcomes and costs. Vaccination was compared with no vaccination, and the cost-effectiveness of vaccination was evaluated from the health system and the societal perspectives. The analysis was run separately in five regions (covering all the 31 provinces of Mainland China) defined by anti-HAV prevalence (around 50%, 50-69%, 70-79%, 80-89% and 90%-). The study projects that with the Chinese low-cost vaccine, vaccination could gain quality adjusted life years (QALYs) through the whole country and save health system or societal costs in the lowest, lower, intermediate and higher infection regions. Vaccination should also be cost-effective in the highest infection region because of low additional costs per QALY gained. However, vaccination would increase the probability of death due to hepatitis A in the highest and higher infection regions by 38 and 37 per million enrolled, respectively, and as vaccine protection loss increases the risk would also occur in intermediate and lower infection regions. The trend that the lower infection level the region has, the more cost-effective vaccination would be is obvious. Sensitivity analyses prove that our conclusions are robust. Considering the potential risk of vaccination, as well as unbalanced socioeconomic developments and significant differences in HAV infection through the whole country, the study suggests that universal childhood hepatitis A vaccination should be first administrated in provinces with the lowest infection level. With knowledge accumulation and further evaluations, the zone of immunization would be considered to be expanded gradually from provinces with lower infection level to those with higher.

[A five-year observation on efficacy of revaccination in children of non-response to hepatitis B vaccine].

OBJECTIVES: To evaluate the long-term efficacy of revaccination in non-responder children to primary hepatitis B (HB) vaccination and to compare the efficacy of low-dose intradermal inoculation to that of routine-dose intramuscular inoculation. METHODS: 40 healthy non-responder children to primary HB vaccination identified by screening were given a three-dose revaccination randomly by intramuscular (n = 17, 10 microg per dose) or intradermal route (n = 23, 2 microg per dose) since September, 1999, and their blood specimens were collected regularly for testing for HB virus markers up to five years. Another 80 responder children to primary HB vaccination were also followed-up as controls without revaccination. By the end of five-year follow-up, HBsAg-specific lymphocyte response was investigated in vitro, and a booster dose (5 microg) was given to those with negative conversion of anti-HBs and their anamnestic responses were evaluated 12-14 days later. RESULTS: Serum anti-HBs did not reach 10 IU/L only in one of 40 non-responder children, who received intradermal revaccination. In the fifth year after revaccination, 50% of the non-responder children who received intramuscular revaccination still maintained anti-HBs of > or = 10 IU/L, though the rate was significantly lower than 85% in controls. Following the booster dose, a robust anamnestic response was developed in all of 8 intramuscular revaccinees and 11 controls but 16 of 18 intradermal revaccinees, who lost anti-HBs of > or = 10 IU/L over time, and geometric mean titers of anti-HBs climbed to 208, 105, and 549 IU/L, respectively. Secretions of HBsAg-specific interleukin-2 and -5 could be detected in peripheral blood mononuclear cell samples of more than 70% of non-responder children. Person-year infection rates of HB virus were 8.9% (8/89.9 person-years) for intradermal revaccinees, significantly higher than 3.6% (12/337.2 person-years) in controls, and 4.3% (3/70.2 person-years) for intramuscular revaccinees, approximating to that of controls, based on positive conversion of anti-HBc. CONCLUSIONS: Three-dose intramuscular revaccination did play an important immune protection for non-responder children to primary HB vaccination, but its efficacy could not reach the level of primary vaccination in responders. Low-dose intradermal inoculation was not as effective as route-dose intramuscular inoculation with the same doses in revaccination for non-responder children to primary HB vaccination.

Hepatitis B revaccination in healthy non-responder Chinese children: five-year follow-up of immune response and immunologic memory.

To assess persistence of anti-HBs and immunologic memory of non-responders after revaccination, 40 healthy non-responder children were given a three-dose recombinant hepatitis B vaccine revaccination randomly by intramuscular (10 microg per dose) or intradermal (2 microg per dose) route and followed up to five years. All 17 intramuscular and 22 of 23 intradermal children developed a seroprotective antibody response (anti-HBs>or=10 mIU/mL) after revaccination. Children of intramuscular group had significantly higher seroprotection rates and anti-HBs geometric mean titers than the intradermal group. At year 5, 50% of children in intramuscular group, but only 18.2% of intradermal group still maintained seroprotection (P=0.075). By the end of follow-up, a booster dose (5 microg) was given to those who had lost seroprotection. All the eight intramuscular children developed an anamnestic response with increase of anti-HBs level by 215 times, but two of the 18 intradermal children failed to produce seroprotective level. Three-routine-dose intramuscular revaccination was significantly more effective than low-dose intradermal revaccination with the same number of injections. No child seroconverted to HBsAg, and 11 had transient infections indicated by seroconversion to anti-HBc. These results demonstrated that non-responders could benefit from three doses intramuscular revaccination not only in high proportion of anti-HBs conversion but also in long-term persistence of seroprotection, and more importantly in preservation of the immunologic memory years after loss of protective anti-HBs.