An economic analysis of adult hepatitis B vaccination in China

Background and objectiveWith the universal infant hepatitis B vaccination (HepB) program, China has made remarkable achievements to prevent and control hepatitis B. In order to further reduce hepatitis B virus (HBV) infection, the Chinese government is considering implementing a widespread adult HBV vaccination campaign. We performed an economic analysis of two different adult HepB vaccination strategies for 21–59-years-olds: vaccination without screening and screening-based vaccination.MethodsCost-benefit analyses were conducted. All 21–59-year-olds were divided into two groups: young adults (ages 21–39) and middle-aged adults (ages 40–59). Costs and benefits were estimated using the direct cost and societal (direct and indirect costs) perspectives. All costs and benefits were adjusted to 2014 US dollars, where future values were discounted at a 3% annual rate. We calculated benefit-cost ratios (BCRs) of the two vaccination strategies for the two different age groups. Sensitivity analyses varied key parameters within plausible ranges.ResultsAmong young adults, the direct and societal BCRs for a vaccination campaign with no screening would be 1.06 and 1.42; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 1.19 and 1.73. Among middle-aged adults, the direct and societal BCRs for a vaccination campaign without screening would be 0.59 and 0.59; with a screening-based vaccination campaign, the model estimated the direct and societal BCRs would be 0.68 and 0.73.ConclusionThe results of our study support a HepB vaccination campaign for young adults. Additionally, a vaccination campaign with screening appeared to provide greater value than a vaccination without screening.     

乙型肝炎病毒致原发性肝细胞癌的作用机制

HBV是引起原发性肝细胞癌(HCC)的重要致病因素,但其确切的发病机制仍不清楚。HBV DNA的整合和HBx蛋白的多种功能(包括反式激活作用、抑制p53等抑癌基因、参与肝细胞凋亡的调控、影响肝细胞遗传学、对肝细胞DNA修复的直接调控),都与HCC致癌作用有关,MHBst、LHBs的作用和雌激素的影响也与HCC的发生相关。     

乙型肝炎病毒相关性原发性肝癌抗病毒治疗的研究现状及展望

HCC是常见的恶性肿瘤之一,HBV感染是引起HCC的最主要原因.合理的抗病毒治疗,可以有效降低HBV相关性HCC的发生率、延长患者生存期及改善患者的预后,从而提高HCC患者的生存质量.此文就抗病毒治疗与HCC发病率及预后的关系进行综述.     

乙型肝炎病毒变异诱发肝细胞癌的分子机制及其研究进展

HBV引起的肝细胞癌居我国恶性肿瘤所致死亡原因的第一位。本文从HBV基因组流行病学入手,系统研究了HBV致癌各阶段病毒进化规律及其与宿主遗传因素的交互作用,综合分析了载脂蛋白B mRNA编辑酶催化多肽家族在炎-癌转化中的桥梁作用,进而提出了普适性“癌症进化发育学”理论体系。癌症进化发育学为理解炎症促进癌症发展的机制奠定...     

广西壮族自治区肝癌高发区HBV基因型、BCP/前C区突变与肝癌相关性的研究

目的 研究广西壮族自治区(广西)扶绥县肝癌高发区HBV基因型、基本核心启动子(BCP)/前C区突变与肝癌的关系。方法 采用病例对照方法收集53例肝癌患者和70例HBV健康携带者的血清,提取HBV DNA,用巢式PCR扩增 HBV S区、BCP/前C区,扩增产物纯化后测序,分析基因型、基因突变与肝癌发生的关系。结果 BCP区A1762T/G1764A及前C区T1858C在病例组中的突变率高于对照组,分别为94.3% vs. 75.7%(P=0.006)和50.9% vs. 31.4%(P=0.029);A1775G在对照组中的突变率高于病例组28.6% vs.13.2%(P=0.041)。多因素logistic回归分析显示,HBV A1762T/G1764A和T1858C突变是肝癌发生的危险因素,OR值分别为5.459(95%CI:1.397~21.332,P=0.015)和3.881(95%CI:1.462~10.305,P=0.006);A1775G突变是肝癌发生的保护因素,OR=0.192(95%CI:0.059~0.622,P=0.006)。结论 HBV C基因型是广西肝癌高发区的主要流行株,HBV BCP区A1762T/G1764A、A1775G、前C区T1858C 突变与HBV相关肝癌的发生有密切关系。     

Endemic hepatitis B virus infection and chronic liver disease mortality in the Republic of Palau, 1990-2002

In the Republic of Palau, a Pacific island nation, approximately 20% of the population is chronically infected with hepatitis B virus (HBV) and is at risk of developing chronic liver disease (CLD), including cirrhosis and hepatocellular carcinoma (HCC). To examine the consequences of HBV infection, we sought to quantify HBV-related CLD mortality in this population. The cause of death was abstracted from death certificates of all persons who died in Palau during 1990-2002. CLD deaths were categorised as cirrhosis or HCC. HBV serological status was determined by review of a hospital database. The cause of death was determined for 1,366 (85%) of 1,608 deaths. CLD was the fifth most common cause of death, accounting for 102 (7%) deaths with a known cause. Of deaths due to CLD, 55 (54%) were from cirrhosis and 47 (46%) were from HCC. Sixty-five percent of CLD decedents and 19% of non-CLD decedents were chronically infected with HBV (P<0.01). The attributable fraction of HBV-related CLD was 54% (58% for cirrhosis and 53% for HCC). CLD mortality rates were approximately twice the worldwide CLD rate. HBV-related CLD is a common cause of death in the Republic of Palau, highlighting the importance of routine infant hepatitis B vaccination, especially in countries with high endemicity.     

Prevalence of chronic hepatitis B virus infection before and after implementation of a hepatitis B vaccination program among children in Nepal

Background

In Nepal, an estimated 2–4% of the population has chronic hepatitis B virus (HBV) infection. To combat this problem, from 2002 to 2004, a national three dose hepatitis B vaccination program was implemented to decrease infection rates among children. The program does not currently include a birth dose to prevent perinatal HBV transmission. In 2012, to assess the impact of the program, we conducted a serosurvey among children born before and after vaccine introduction.

Methods

In 2012, a cross-sectional nationally representative stratified cluster survey was conducted to estimate hepatitis B surface antigen (HBsAg) prevalence among children born from 2006 to 2007 (post-vaccine cohort) and among children born from 2000 to 2002 (pre-vaccine cohort). Demographic data, as well as written and oral vaccination history were collected. All children were tested for HBsAg; mothers of HBsAg positive children were also tested. Furthermore, we evaluated the field sensitivity and specificity of the SD Bioline HBsAg rapid diagnostic test by comparing results with an enzyme immunoassay.

Results

Among 2181 post-vaccination cohort children with vaccination data by either card or recall, 86% (95% confidence interval [CI] 77–95%) received ≥3 hepatitis B vaccine doses. Of 1200 children born in the pre-vaccination cohort, 0.28% (95% CI 0.09–0.85%) were positive for HBsAg; of 2187 children born in the post-vaccination cohort, 0.13% (95% CI 0.04–0.39%) were positive for HBsAg (p = 0.39). Of the six children who tested positive for HBsAg, two had mothers who were positive for HBsAg. Finally, we found the SD Bioline HBsAg rapid diagnostic test to have a sensitivity of 100% and a specificity of 100%.

Conclusions

This is the first nationally representative hepatitis B serosurvey conducted in Nepal. Overall, a low burden of chronic HBV infection was found in children born in both the pre and post-vaccination cohorts. Current vaccination strategies should be continued.     

Effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia 21 years after its introduction

Hepatitis B is a viral disease of global importance. In Catalonia in the 1980s, the seroepidemiological pattern of HBV infection was low-intermediate. In 1990, the Expert Committee on Vaccinations of the Department of Health of the Generalitat of Catalonia evaluated the systematic introduction of hepatitis B vaccination in preadolescents, maintaining the vaccination of risk groups. The objective of this study was to estimate the effectiveness and impact of the systematic hepatitis B vaccination programme in preadolescents in Catalonia 21 years after its introduction. A retrospective cohort study was conducted, comparing the disease incidence in vaccinated and unvaccinated cohorts. Cases of hepatitis B were defined as those reported by the General Subdirectorate of Surveillance and Response to Public Health Emergencies between 2000 and 2014. The incidence rate was 2.5 per 100,000 persons in 1991 and 1.2 per 100,000 persons in 2014, a reduction of 52%. During the study period, 388 cases of hepatitis B infection were notified, of which three were classified as vaccine failures. Vaccine effectiveness was 99.30% (95% CI: 97.83–99.78) and the population prevented fraction in the cohorts of preadolescents studied was 64.56% (95% CI: 60.45–68.66). The effectiveness and impact of the hepatitis B vaccination program in preadolescents in Catalonia is high, with the consequent benefits for the population.     

Impacts of human leukocyte antigen DQ genetic polymorphisms and their interactions with hepatitis B virus mutations on the risks of viral persistence,liver cirrhosis,and hepatocellular carcinoma

Human leukocyte antigen (HLA)-DQ genetic polymorphisms have been associated with chronic hepatitis B virus (HBV) outcomes. We aimed to determine impacts of HLA-DQ polymorphisms and their interactions with HBV mutations on the risks of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). rs2856718 (A > G) and rs9275319 (A > G) were genotyped in 1342 healthy controls, 327 HBV surface antigen (HBsAg) seroclearance subjects, 611 asymptomatic HBsAg carriers (ASCs), 1144 chronic hepatitis B (CHB) patients, 734 LC patients, and 1531 HCC patients using quantitative PCR. HBV mutations were detected by direct sequencing. Logistic regression analyses were utilized to assess the factors and/or multiplicative interactions significantly associated with liver diseases. rs9275319 variant genotypes were inversely associated with HBV persistence compared to HBV natural clearance subjects. rs2856718 variant genotypes significantly increased LC risk compared to ASCs plus CHB patients (GG vs. AA: odds ratio [OR], 1.52, 95% confidence interval [CI], 1.17–1.97 and AG + GG vs. AA: OR, 1.27; 95% CI, 1.04–1.54) and decreased HCC risk compared to HCC-free HBV-infected subjects (AG vs. AA: OR, 0.76; 95% CI, 0.65–0.89 and AG + GG vs. AA: OR, 0.78, 95% CI, 0.68–0.90). rs2856718 variant genotypes were significantly associated with an increased frequency of HBV A1726C mutation, a LC-risk, HCC-protective mutation, in genotype C. A rs9275319 variant genotype (GG) was significantly associated with an increased frequency of preS1 start codon mutation, an HCC-risk mutation, in genotype C. The interaction of rs2856718 AG + GG genotype with T1753V, a HCC-risk mutation, significantly reduced LC risk, with an OR of 0.26 (95% CI, 0.09–0.78); whereas the interaction of rs2856718 AG genotype with C1673T, a LC-risk mutation, significantly increased HCC risk, with an OR of 2.80 (95% CI, 1.02–7.66) in genotype C HBV-infected subjects. Conclusively, the HLA-DQ polymorphisms affect the risks of LC and HCC differently in chronic HBV-infected subjects, possibly via interacting with the HBV mutations.     

1990-2016年中国乙型肝炎引起的肝硬化及其他慢性肝病疾病负担变化趋势分析

目的分析1990-2016年中国乙型肝炎引起的肝硬化及其他慢性肝病导致的疾病负担变化情况,为其防治策略的制定提供科学依据。方法利用2016年全球疾病负担(GBD2016)研究结果,分析1990-2016年中国乙型肝炎引起的肝硬化及其他慢性肝病的患病率、死亡率和伤残调整寿命年(DALY)的变化趋势。结果与1990年相比,中国2016年乙型肝炎引起的肝硬化及其他慢性肝病患病和死亡人数分别增加了79.6%和2.4%。患病率增加了49.2%,男性患病率的增幅(50.3%)高于女性(42.3%),15~49岁年龄组人群患病率增幅最大(33.2%)。男性死亡数和DALYs数均呈现上升的趋势,变化率分别为13.6%和2.2%。2016年,年龄标化DALY率排名前五位的省份为青海省(314.6/10万)、贵州省(303.1/10万)、云南省(262.4/10万)、广西壮族自治区(239.6/10万)和台湾省(227.2/10万)。结论1990-2016年,我国乙型肝炎引起的肝硬化及其他慢性肝病患病情况呈现上升趋势,重点为男性和15~49岁年龄组的人群,不同省份疾病负担情况分布不均,防治工作依然不容忽视。     

中国1992-2019年乙型肝炎疫苗免疫及母婴阻断策略的成本效益分析

目的:对我国1992-2019年来实施的乙型肝炎（乙肝）疫苗（HepB）免疫及母婴阻断策略进行卫生经济学评价,为我国乙肝防控策略提供参考。方法:构建决策分析马尔科夫模型,对1992-2019年中国出生的新生儿队列进行分析。模型参数主要来自于文献、年鉴、中国CDC。采用单因素敏感性分析验证模型结果的稳定性。结果:1992...     

Hepatitis B testing,care linkage,and vaccination coverage within a registry of hepatitis C infected patients

Background

Hepatitis B virus (HBV) infection testing among persons with hepatitis C virus (HCV) infection is necessary to appropriately care for these patients, yet uptake of HBV testing and vaccination in this population is suboptimal.

基于GWAS的乙肝相关肝癌关联lncRNA SNPs生物信息学分析

目的 利用生物信息学方法挖掘乙肝相关肝癌相关的lncRNA SNPs,为肝癌生物标志物筛选及致病机制研究提供线索和方向。方法 通过SNAP工具获取GWAS识别的乙肝相关肝癌关联SNPs的易感区域。结合dbSNP和lncRNASNP等数据库匹配易感区域上的lncRNA SNPs,并采用rVarBase、HaploReg等数据库对SNPs进行功能注释。利用TCGA数据库的乙肝相关肝癌基因表达数据进行lncRNA的差异表达分析。结果 基于GWAS和生物信息学工具共挖掘9个具有潜在功能的lncRNA SNPs(lnc-RP11-150O12.3 rs1008547、rs11776545、rs2275959、rs2298320 rs2298321和lnc-ACACA-1 rs7221955、rs9891142、rs9896574、rs9908998)。功能注释结果表明所有SNPs均位于染色质交互区域或转录因子结合位点;肝组织的组蛋白修饰标识显示多数SNPs位于启动子区或增强子区,且为DNase超敏感位点,可破坏转录因子的结合基序;其中3个SNPs在HepG2细胞系中被发现影响蛋白质结合。此外,两个lncRNAs在乙肝相关肝癌患者癌组织中的表达均高于癌旁组织。结论 lnc-RP11-150O12.3和lnc-ACACA-1上的9个SNPs具有潜在生物学功能,在乙肝相关肝癌的发生和发展中可能发挥重要作用。     

Induction of a robust T- and B-cell immune response in non- and low-responders to conventional vaccination against hepatitis B by using a third generation PreS/S vaccine

Non-responsiveness to conventional hepatitis B vaccines in individuals at high risk of exposure to hepatitis B virus (HBV) is an important public health problem and of particular relevance in health care providers. Yeast-derived conventional HBsAg vaccines fail to induce protective antibody titers in up to 10% of immune competent vaccinees. Therefore, a third generation HBV vaccine, Sci-B-Vac™, was developed which contains in addition to the small S antigen the PreS1 and PreS2 antigens. This vaccine proved to induce a highly potent cellular and humoral immune response in healthy individuals as well as protective antibody levels in non- and low-responders to conventional HBV vaccines. The aim of the study was to examine whether Sci-B-Vac™ triggers cellular and humoral immunity in individuals who failed immunization with conventional vaccines. We immunized 21 volunteers (15 non- and 6 low-responders) according to the standard vaccination schedule (0, 4 and 24 weeks), determined the cellular immunity by proliferation assay and interferon (IFN)-γ ELISpot and measured the anti-HBs antibody titers prior to each vaccination and four weeks after the third vaccine dose. Following three vaccinations, PreS/S-specific T-cell proliferation was detected in 8 out of 15 non-responders and 5 out of 6 low-responders. Specific IFN-γ responses were measured in 2 out of 15 non-responders and 4 out of 6 low-responders. All but one (20/21) study participants developed anti-HBs titers ≥10 IU/l after three vaccinations. Anti-HBs ≥100 IU/L were detected in 12 out of 15 non-responders and in 6 out of 6 low-responders. Anti-HBs ≥10 IU/l and <100 IU/l were found in 2 non-responders. These results indicate that Sci-B-Vac™ induces cellular immunity as well as protective anti-HBs antibody titers in non- and low-responders. In conclusion, these results confirm that Sci-B-Vac™ should be administered to non-responders to conventional HBV vaccines and patients with impaired immune function.     

血清GP73、HSP27联合AFP检测在HBV相关早期肝细胞癌诊断的价值

目的 探讨高尔基蛋白73(GP73)、热休克蛋白27(HSP27)联合甲胎蛋白(AFP)检测在乙型肝炎相关性早期肝细胞癌诊断中的价值。 方法 选择50例HBV相关早期肝细胞癌患者、50例乙肝肝硬化患者和30名健康人,采用酶联免疫吸附试验(ELISA)检测GP73、HSP27水平,电化学发光法检测AFP含量。实时荧光定量PCR方法测定肝癌患者的HBV-DNA水平。 结果 早期肝癌组患者血清GP73、HSP27、AFP水平分别为(266.37±98.41)ng/ml、(847.18±211.72)pg/ml、(368.56±65.32)ng/ml,明显高于肝硬化组[(60.23±32.30)ng/ml、(338.46±114.3)pg/ml、(26.22±8.58)ng/ml]、以及对照组[(23.32±11.08)ng/ml、(73.39±38.54)pg/ml、(7.15±3.32)ng/ml],差异有统计学意义(均P<0.01);早期肝癌组患者血清AFP、GP73、HSP27单项检测阳性率分别为75%、82%、74%,及AFP+GP73+HSP27联合检测的阳性率为86%,均明显高于肝硬化组(分别为48%、37.5%、18%、32%)及健康对照组(分别为3%、6%、0、0)(均P<0.01),其中AFP+GP73+HSP27联合检测阳性率最高(P<0.01);AFP、GP73及HSP27与HBV-DNA的相关性为0.076、0.119、0.176(P>0.05)。 结论 GP73、HSP27与AFP联合检测可作为诊断肝细胞癌的重要指标,为早期发现及治疗提供依据,它们与HBVDNA情况无关。     

Immunogenicity and safety of an investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal insufficiency who failed to respond or to maintain antibody levels after prior vaccination: results of two open, randomized, comparative trials

An investigational AS02_v-adjuvanted hepatitis B (HB-AS02) was compared with a licensed conventional recombinant hepatitis B vaccine (HBVAXPRO™; Sanofi Pasteur MSD, Lyon, France) in pre-dialysis, peritoneal dialysis and hemodialysis patients aged ≥18 years who had failed either to respond to prior vaccination with a conventional hepatitis B vaccine (Study A; n = 251) or to maintain protective antibody concentrations after prior hepatitis B vaccination (Study B; n = 181). These were open, randomized, comparative trials. Mean (range) age was 65.9 (31-92) and 64.6 (29-92) years in the two studies, respectively. In Study A, two doses of HB-AS02 given one month apart were found to be superior to two doses of the licensed vaccine in terms of seroprotection rate (76.9% versus 37.6%) and anti-HBs geometric mean antibody concentration (GMC; 139.3 versus 6.9 mIU/ml), with antibody concentrations ≥100 mIU/ml in 61.1% and 15.4% of subjects in the two groups, respectively. In Study B, one month after administration of a single booster dose, seroprotection rates were 89.0% in the HB-AS02 group and 90.8% in the licensed vaccine group, 81.3% and 60.9% of subjects had antibody concentrations ≥100 mIU/ml, and anti-HBs GMCs were 1726.8 and 189.5 mIU/ml. HB-AS02 was found to be more reactogenic than the licensed vaccine. In summary, the investigational HB-AS02 vaccine induced higher seroprotection rates and anti-HBs GMCs than a licensed conventional hepatitis B vaccine in uremic patients who had failed to respond or to maintain protective antibody titers after prior hepatitis B vaccination.     

Assessing the impact of the routine childhood hepatitis B immunization program and the need for hepatitis B vaccine birth dose in Sierra Leone, 2018

Sierra Leone is highly endemic for hepatitis B virus (HBV) infection and thus recommends three doses of hepatitis B vaccine (HepB3) from 6 weeks of age but does not recommend a birth dose (HepB-BD) to prevent mother-to-child transmission (MTCT). We evaluated impact of the existing HepB3 schedule and risk for MTCT of HBV. We conducted a community-based serosurvey among 4–30-month-olds, their mothers, and 5–9-year-olds in three districts in Sierra Leone. Participants had an HBV surface antigen (HBsAg) rapid test; all HBsAg-positive and one HBsAg-negative mother per cluster were tested for HBV markers. We collected children’s HepB3 vaccination history. Among 1889 children aged 4–30 months, HepB3 coverage was 85% and 20 (1·3% [95% CI 0·8–2·0]) were HBsAg-positive, of whom 70% had received HepB3. Among 2025 children aged 5–9 years, HepB3 coverage was 77% and 32 (1·6% [1·1–2·3]) were HBsAg-positive, of whom 56% had received HepB3. Of 1776 mothers, 169 (9·8% [8·1–11·7]) were HBsAg-positive. HBsAg prevalence was 5·9% among children of HBsAg-positive mothers compared to 0·7% among children of HBsAg-negative mothers (adjusted OR = 10·6 [2·8–40·8]). HBsAg positivity in children was associated with maternal HBsAg (p = 0·026), HBV e antigen (p < 0·001), and HBV DNA levels ≥ 200 000 IU/mL (p < 0·001). HBsAg prevalence was lower among children than mothers, for whom HepB was not available, suggesting routine infant HepB vaccination has lowered HBV burden. Since HBsAg positivity in children was strongly associated with maternal HBV infection and most of the HBsAg-positive children in the survey received HepB3, HepB-BD may prevent MTCT and chronic HBV infection.     

The impact of the COVID-19 pandemic on hepatitis B virus vaccination and transmission among men who have sex with men: A mathematical modelling study

BackgroundDuring the COVID-19 pandemic, the number of hepatitis B virus (HBV) vaccinations among men who have sex with men (MSM) has been considerably lower than before the pandemic. Moreover, less frequent HBV testing and a reduction in numbers of sex partners have been reported. We assessed the impact of these COVID-19-related changes on HBV transmission among MSM in the Netherlands.MethodsWe estimated the changes in sexual activity, HBV testing, and HBV vaccination among MSM during the pandemic from Dutch data. We used a deterministic compartmental model and investigated scenarios with small or large declines in sexual activity, testing, and vaccination for the current phase of the pandemic (without available data). We examined the increase in HBV vaccinations needed to prevent further increase in HBV incidence.ResultsWith a decrease in numbers of sex partners of 15–25% during the first lockdown and 5% during the second lockdown, we found a decline of 6.6% in HBV incidence in 2020, despite a >70% reduction in HBV testing and vaccination during the first lockdown. With numbers of sex partners rebounding close to pre-pandemic level in 2021, and a reduction of 15% in testing and 30% in vaccination in 2021, we found an increase of 1.4% in incidence in 2021 and 3.1% in 2026. With these changes, an increase of ≥60% in HBV vaccinations in 2022 would be needed to bring the HBV incidence in 2023 back to the level that it would have had if the COVID-19-related changes had not occurred.ConclusionsDespite reductions in sexual activity during the COVID-19 pandemic, the decrease in HBV vaccinations may result in a small increase in HBV incidence after 2021, which may persist for years. It is important to restore the vaccination level and limit further increase in HBV transmission among MSM.