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 / 中华医学杂志(英文版)

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.

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 / 中华医学杂志(英文版)

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.

Quantitative study of iron metabolism-related genes expression in rat / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the multiple iron metabolism-related genes expression, its regulation by iron and the expression correlation among the genes in rat tissues.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Cost-utility analysis on universal childhood hepatitis A vaccination in regions with different anti-HAV prevalence rates of China / 中华流行病学杂志

Objective To explore the inputs and outputs of areas with different anti-HAY 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 nonvaccination group to evaluate the number of symptomatic infection,hospitalization,death,qualityadjusted 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 systen 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.

Effect of plasma-derived hepatitis B vaccine 23(rd) year after a full course of vaccination in healthy young children / 中华预防医学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

A five-year observation on efficacy of revaccination in children of non-response to hepatitis B vaccine / 中华预防医学杂志

<p><b>OBJECTIVES</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>