A nationwide vaccination programme in Italy against hepatitis B virus infection in infants of hepatitis B surface antigen-carrier mothers

In order to prevent hepatitis B virus (HBV) infection of infants of hepatitis B surface antigen (HBsAg)-positive mothers, a nation-wide immunization programme was initiated in Italy in January 1984. During the first 3 years (1984-86), 651,667 out of 1726,000 pregnant women (37.8%) were screened for HBsAg; the percentage of mothers screened increased from 32% in 1984 to 51% in 1986 in 15 of the 21 Italian regions, where data by year were available. HBsAg was present in 15,640 mothers (2.4% of those screened); range by region 0.3-6.4%. All newborns of HBsAg-positive women, regardless of the mother's status of hepatitis Be antigen (HBeAg), were given a single dose (0.5 ml Kg-1) of a hepatitis B immune globulin within 24 h after birth and the first dose of plasma-derived hepatitis B vaccine within 7 days after birth. The immunization coverage rate was 80% in the 3-year period. Protective antibodies were found in greater than 97% of a sample of 1071 infants, immunized from different regions. No serious reactions were observed. On the basis of this field experience, it may be concluded that a nation-wide hepatitis B vaccination programme for infants of HBsAg-carrier mothers would be highly immunogenic and safe. Its implementation, however, requires continuous public education and cooperation from physicians.     

预防手术患者经手术感染乙型肝炎病毒

目的探讨手术患者经手术感染乙型肝炎病毒(HBV)的防护方法。方法在HBV传染性定量和测定HBV经手术传播感染阈值的基础上,探讨手术患者经手术感染HBV的防护方法。结果 HBV经手术传播的感染阈值为105ID/ml,HBsAg阳性、HBeAg阴性和阳性者中传染源比率分别为19.2%、3.2%和83.9%;HBV经双层手套传播的防护阈值为106ID/ml,HBsAg阳性和HBeAg阳性者中传染源比率分别为14.7%和67.8%;以103ID/ml为禁止外科医师做手术的淘汰阈值。结论手术患者感染HBV的主要传染源是外科医师,禁止可能成为传染源的外科医师从事具有侵入性的医疗操作是有效的防护方法,如何识别外科医师中的传染源是制定具体防护措施的关键所在。     

Chronic hepatitis B virus infection

Many factors are involved in the pathogenesis of chronic hepatitis B virus infection (HBV), such as, for example, characteristics of the virus, ethanol intake, coinfection with other viruses (HCV, HIV, HDV), and therapeutic interventions such as the use of cytotoxic drugs or immunosuppressors, or specific antiviral agents. The clinical, pathological and serological characteristics of chronic hepatitis B virus infection are besides very heterogeneous. Chronic HBV infection can be recognised facing persistence of the Australia antigen (HBsAg) for more than six months. The presence of HBeAg is usually associated with active viral replication and can be measured by the quantity of DNA-HBV present in the serum or by the hepatic expression of HBcAg. The hepatic damage that is produced in chronic hepatitis due to HBV is not so much due to the effect of the virus on the hepatocytes as to the immune reaction that it provokes in the host. For this reason a certain inversely proportionate correlation can be observed between the intensity of viral replication and the degree of hepatic inflammation. The presence of active chronic hepatitis in the initial biopsy has not been associated with the development of cirrhosis, nor does the histological diagnosis of persistent chronic hepatitis guarantee that cirrhosis will be developed in the future.     

Hepatitis C virus, hepatitis B virus and human immunodeficiency virus infection in pregnant women in North-East Italy: A seroepidemiological study

Background: Pregnant women can be considered a sentinel population, because they are a relatively unselected population whose prevalence data may be extended to the general population. Methods: A seroepidemiological study was carried out in Padua (North-East Italy) to assess the epidemiological aspects of HCV, HBV and HIV infection in 2059 pregnant women consecutively seen at the Department of Obstetrics and Gynaecology during 1996. Out of them, 1804 (87.2%) were indigenous and 255 (12.8%) immigrants. Sociodemographical and sanitary data were collected for each woman. Results: The overall prevalence of anti-HCV was 1.9% (42.5% with detectable HCV-RNA); HBsAg was found in 1.0%; the prevalence of anti-HIV was 0.3%. Findings are substantially consistent with the epidemiological picture of such infections in the general population of our geographic area. A parenteral risk factor for HCV infection was found in 19 subjects (47.5%): 18 were intravenous drug users and 1 a blood transfusion recipient. HBsAg seroprevalence was higher in immigrants than in autochthonous (3.1% vs. 0.7% respectively, p < 0.01). One of the 6 anti-HIV positive women was intravenous drug user. Logistic regression analysis was carried out for each viral agent to determine which characteristics were independently associated with infection: anti-HCV prevalence resulted independently associated to Italian origin (OR: 3.7), unmarried status (OR: 2.7), unemployed condition (OR: 6.1) and history of previous abortion (OR: 2.8). HBsAg prevalence was independently associated to unemployed condition (OR: 10.8), whereas HIV positivity was significantly related to the unmarried status (OR: 18.5). Conclusion: Our study pinpoints the need of screening all pregnant women for HCV and HIV infection, in addition to the HBsAg screening which is compulsory in Italy.     

儿茶素类抗乙型肝炎病毒的效果观察

目的观察儿茶素类抗乙肝病毒和保肝降酶作用.方法用1日龄北京雏鸭制备鸭乙型肝炎病毒(DHBV)模型,设儿茶素类给药组(60、120和240 mg/kg)、阳性药物对照组(Are-AMP)、模型组和阴性对照组.取血清用斑点杂交法(dig标记探针)测DHBV*DNA,用单抗夹心ELISA法测定DHBsAg;检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)活性观察肝功能变化,并作肝组织病理切片观察形态学改变.结果儿茶素类各给药组鸭血清DHBV*DNA和DHBsAg含量均有降低,与给药前和模型组相比差异有显著性;给药25 d及停药后14 d,鸭血清ALT与AST活性均降低;给药后的肝组织病理变化有明显改善. 结论儿茶素类有抗乙肝病毒、降低转氨酶活性、减轻肝脏病理损伤作用.     

Acute infection by hepatitis B virus

The clinical spectrum of acute hepatitis B virus infection is very broad, with clinical manifestations that range from anicteric and sub-clinical hepatitis to severe acute icteric hepatitis and even, in some cases, to fulminant hepatitis. Diagnosis depends to a large extent on the degree of clinical suspicion of hepatitis, establishing the aetiological origin of the B virus through the study of serological markers and/or DNA in the blood. Although in the majority of cases there is a favourable evolution of acute hepatitis B virus infection, with spontaneous resolution of the clinical manifestations in 4-8 weeks, progression to chronic hepatitis is not unusual in certain cases, above all in infancy. No specific treatment exists for acute hepatitis B virus infection that would reduce its severity or prevent its evolution into chronic hepatitis. However, relative rest and the administration of an hypercaloric diet are recommended. In cases of severe acute hepatitis hospital admission should be recommended; in cases of fulminant hepatitis, admission to the intensive care unit for intensive monitoring and evaluation of a liver transplantation is recommended if spontaneous improvement does not occur. This paper reviews briefly the clinical manifestations, diagnosis, prognosis and treatment of acute hepatitis B virus infection.     

中国成人乙型肝炎免疫预防技术指南

  目的   了解湖北省襄阳市和孝感市15～59岁居民乙肝疫苗的接种情况、未种原因和影响因素,为制定成人乙肝防控策略提供依据。  方法  于2020年3 — 11月,采用多阶段随机抽样的方法在襄阳市和孝感市抽取15～59岁居民进行问卷调查,应用χ²检验和二元logistic回归分析数据。  结果  本次共收到有效问卷1398份,乙肝疫苗接种率为65.38 %（914/1398）,乙肝疫苗的全程接种率为37.7 %（527/1398）。无乙肝疫苗接种史的484人中,308人（63.64 %）愿意接种乙肝疫苗。最主要的未种原因是认为“自己身体很健康,不需要接种”。多因素分析结果显示,职业、受教育程度、月收入、周围有无乙肝患者是乙肝疫苗接种的影响因素。  结论  农民、低教育水平、高收入是影响乙肝疫苗接种的危险因素,周围有乙肝患者的居民更重视乙肝疫苗的接种。     

我国乙型肝炎疫苗接种前筛检策略的优化

By means of decision tree model and cost-effectiveness analysis 15 kinds of programmes which may be used for hepatitis B virus markers screening in vaccination were evaluated. The results showed that the most cost-effective alternative was to identify the negatives for anti-HBc again after testing for anti-HBs and vaccinating all test negatives. That is to say it must not be adopted for persons to be tested for HBsAg, anti-HBs and anti-HBc before being vaccinated. Sensitivity and threshold analysis were also done to determine the effects of changes in the costs of vaccine and screening tests.     

Factors affecting the compliance of the antenatal hepatitis B screening programme in Italy

The effectiveness in the prevention of perinatally transmitted HBV infection was assessed in 11858 pregnant women consecutively recruited in public and private hospitals in six Italian regions during a 2 months period in 2001. Of them 10881 (91.8%) attended HBsAg antenatal screening. The overall HBsAg prevalence was 1.7% (CI 95%: 1.4-1.9); it was 1.4% (CI 95%: 1.2-1.7) in pregnant women born in Italy but 5.9% (CI 95%: 4.1-8.1) in those born in Asia, Africa, central and south America, and eastern Europe. Results of multiple logistic regression analysis indicate that birth in foreign countries (OR 2.0; CI 95%: 1.3-3.0), family size with more than 4 members in the household (OR 3.5; CI 95%:2.7-4.6), and birth in a private hospital (OR 1.9; CI 95%: 1.3-2.8) were all independent predictors of lack of adherence to HBsAg screening. Out of the 182 new-borns of HBsAg positive mothers 172 (95.0%) were given active plus passive immunisation; this figure was 100% in new-borns of foreign mothers. These findings evidence a good effectiveness in the prevention of perinatally transmitted HBV in Italy. More efforts should be addressed to improve the effectiveness of the programme among foreign pregnant women who have high rate of HBsAg and more likely escape HBsAg screening than Italian pregnant women.     

乙型肝炎病毒基因型与感染临床表型的相关性研究

目的 调查乙型肝炎病毒(HBV)基因型分布,并探讨其与感染临床表型的相关性.方法 采用PCR扩增后测序的方法,对150例乙型肝炎病毒感染者进行HBV基因型的分析,应用x2检验和t检验法分析HBV基因型与临床表型的相关性.结果 150例样本中,B基因型90例占60.0％,C基因型60例占40.0％,不同性别之间HBV基因型分布,差异无统计学意义;B基因型患者年龄(29.4±10.2)岁显著低于C基因型患者(35.1±11.5)岁(P＜0.05);肝硬化和肝细胞癌组C基因型的比例,分别为59.1％和60.0％,显著高于慢性乙型肝炎患者(32.0％)和HBV无症状携带者(30.0％)(P＜0.05);C基因型HBeAg阳性率(71.7％)显著高于B基因型(55.6％)(P＜0.05);C基因型患者血清的HBV-DNA含量(5.98±0.76)log值显著高于B基因型组(5.62±0.92)log值,差异有统计学意义(P＜0.05).结论 HBV基因型与临床病情密切相关,C基因型患者平均年龄、病毒水平、HBeAg阳性率显著高于B基因型,可能是导致C基因型患者更易发展为肝硬化和肝癌的原因.     

乙型肝炎病毒X基因变异与隐匿性感染的关系

隐匿性HBV感染指患者血清HBsAg阴性,而血清和(或)肝组织HBV DNA阳性,其发生机制仍未明了.目前,对HBV基因变异的研究大多集中在S基因,而X基因是病毒复制的重要调节区,是转录、反转录和正链合成的起点,此处变异可能会影响到病毒的转录和复制,但由于X基因结构和功能的复杂性,目前对其变异与隐匿性HBV感染的关系研究相对较少.此文就HBV X基因变异对隐匿性HBV感染的发生和影响进行综述.     

Occupational hepatitis B virus infection in sewage workers

In a cross-sectional study the employees of a Sewage Company were tested for hepatitis B virus (HBV) markers--HBsAg, anti-HBs, anti-HBc--to determine the prevalence of HBV infection and assess the risk of exposed sewage workers becoming infected, so as to evaluate the necessity for appropriate vaccination. The overall prevalence of HBV markers was 43.9% and 6.6% of the employees were HBsAg carriers. In the univariate analysis the prevalence of past and current infection was significantly associated with exposure to sewage (p < 0.001), age (p < 0.001) and with educational level (p < 0.001). However, the logistic regression analysis confirmed that only exposure to sewage was independently associated with positivity for HBV infection (p < 0.001). Workers exposed to sewage should therefore be considered for vaccination against hepatitis B virus.     

Hepatitis B virus infection in children in Sardinia,Italy

Possible hepatitis B immunization of all newborns, regardless of the mother's HBsAg status, is a strategy under consideration for selected hyperendemic areas in Italy. Sardinia is one such area. However, in 1987 in Sardinia, the prevalence of hepatitis B markers in children under 11 years was estimated at 1.7% and the prevalence of hepatitis B surface antigen (HBsAg) at 0.2%. A much higher prevalence of HBsAg was recently observed among adults in this area: 8.7% among men and 5.2% among pregnant women. This contrasting pattern is unlikely to be due to bias: the sampling procedures adopted were appropriate and the percentage of refusals was very low (2.2%). The observed low hepatitis B marker prevalence in young age groups might be the result of a cohort effect due to the improved socio-economic conditions and changes in behaviour that have occurred in Sardinia over the last few years.The finding of only 3 HBsAg+ individuals out of 1,826 children tested, in spite of the 5.2% HBsAg prevalence among pregnant women in that region, is probably attributable to the low proportion of HBeAg positive individuals among the HBsAg+ carrier mothers in this area.At present, immunization of all newborns in Sardinia cannot be recommended.     

隐匿性HBV感染的研究

隐匿性HBV感染的存在和临床意义已经被许多研究所证实,且发现在单纯抗-HBc阳性者中发生率最高.此文就各类人群隐匿性HBV感染的若干研究作了综述.     

Treatment of chronic hepatitis B virus infection

The treatment of the patient with chronic hepatitis B virus infection (HBV) must be carried out with the knowledge that the percentage of patients infected with the B virus that develop chronic hepatitis remains between 5-10%. Of these, 10-30% will present chronic infection with active viral replication, necroinflammatory hepatic lesion, evolution to hepatic cirrhosis and the risk of developing hepatocarcinoma. For this reason, the aim of treatment is to achieve negativisation of the HBeAg, seroconversion to anti-HBe and a reduction of viral replication to undetectable values (estimated by level of DNA-HBV), for protracted periods of time. When a sustained loss of HBeAg and a reduction of viral replication are obtained, a biochemical, clinical and histological remission is achieved. Up until now the therapeutic alternatives in chronic infection by the B virus have been immunomodulation with Interferon alpha and the blocking of viral replication with lamivudine or adefovir dipivoxil. A difference must be drawn between the biochemical response, defined as a fall in the transaminases to normal values, and the virological response, which refers to a fall in the levels of DNA-HBV below 10(5) copies/ml. Finally, the complete response is defined as the virological and biochemical response with negativisation of the HBsAg. If a sustained response is obtained for several months, a histological response can be predicted with reduction in the intensity of the hepatic lesion and an absence or stabilisation in the process of fibrosis. The sustained response should last for no less than 6 to 12 months following the end of treatment.     

Validation of biocides against duck hepatitis B virus as a surrogate virus for human hepatitis B virus

The use of a surrogate virus, namely duck hepatitis B virus (DHBV), has been recommended for testing the virucidal activity of chemical biocides against hepatitis B virus. To date, however, this model has not been recognized as a standard test in European countries, as its laboratory use is associated with considerable difficulties. As previous studies have demonstrated, several alternative procedures may improve the validation of DHBV infection in a cell culture system. Using indirect immunofluorescent antigen staining and the light cycler real-time polymerase chain reaction (PCR) technique, the virucidal activity of peracetic acid (PAA), povidone-iodine (PVP-I) and formaldehyde was tested against DHBV obtained from congenitally infected ducks or prepared from the transfected hepatoma D2 cell line. The results demonstrated that inactivation of DHBV from the D2 cell line was achieved with lower concentrations of the biocides and within shorter exposure time intervals. These lower concentration-exposure time values for DHBV from D2 cells in comparison with DHBV from infected ducks indicated a higher sensitivity of the virus derived from D2 cells. In addition, concentrations of PAA and PVP-I that significantly inactivated DHBV in suspension tests were not able to destroy the viral genome. In conclusion, DHBV from congenitally infected ducks should be used for virucidal testing of chemical biocides against DHBV; DHBV prepared from D2 cells is unsuitable due to its higher sensitivity to biocides. Indirect immunofluorescent staining allows reliable detection of DHBV infectivity, whereas the hepadnavirucidal effect can be evaluated by quantitative PCR.     

乙肝疫苗免疫人群乙肝病毒感染和发病状况研究

目的了解上海市儿童乙肝疫苗免疫后乙肝病毒感染和发病情况。方法采用多阶段随机抽样方法,于2000年和2006年共计抽取1 904份接种人群血液标本,用酶联免疫吸附试验（ELISA）检测HBsAg、抗-HBs和抗-HBc。结果新生儿乙肝疫苗接种率和及时率均保持较高水平。20岁以下人群乙肝发病率明显下降;HBsAg携带率降幅为78.34%。儿童乙肝患者中84.35%（124/147）未接种过乙肝疫苗;23例接种乙肝疫苗但患病的儿童中,12例患儿的母亲或父亲HB-sAg阳性。结论儿童接种乙肝疫苗是预防和降低乙肝感染的有效措施。需加强母（父）婴阻断和家庭内传播机制的研究。     

The cost-effectiveness of alternative strategies against HBV in Italy

Introduction

Nowadays, guidelines for the management of HBV infection in Italy, recommend using vaccines but the screening test among non-vaccinated people is useful to detect people that have a clear presence of the virus without symptoms of the disease. Thanks to the screening test, people infected with HBV are administered traditional therapy in order to stop the progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). These diseases cause the decrease of Qol and cause a high consumption of resources for the health system. The aim of this study is to evaluate the cost-effectiveness of a strategy (test strategy) involving the administration of the screening test to patients at risk and the treatment of the infected according to the protocol therapy. This programme is compared with a strategy (no test strategy) which does not include a screening and treats patients affected by cirrhosis or HCC.

Methods

We created a Markov model following the natural history of the disease and considering the antigen HBeAg to evaluate the cost effectiveness of the test strategy. The analysis was carried out considering a third-party payer perspective. The time horizon considered was 40 cycles of one year. Patients who resulted positive to the test were administered either interferon treatment; or lamivudine or adefovir or entecavir or tenofovir, consistently with the Italian guidelines. Treatments were administered to patients included in the no-test arm after cirrhosis symptoms or HCC.

Results

The results of the base case analysis show that patients following the test strategy compared with patients of the no-test approach cost €17,179/QALY. The Monte Carlo simulation based on a probabilistic sensitivity analysis points out that in 95% of the scenarios assumed, the cost per QALY would be under a hypothetical threshold of €40,000 which is the amount that international guidelines for decision makers are likely to consider sustainable for a health system. In conclusion, anti-hbv test to all high-risk categories should be highly recommended.     

Seroepidemiology of infection with hepatitis A virus and hepatitis B virus in the Seychelles

A batch of 417 serum samples obtained from native-born subjects were tested for the presence of hepatitis B surface antigen (HBsAg) and corresponding antibody (anti-HBs), by enzyme-linked immunosorbent assay (ELISA); and antibodies to hepatitis B core antigen (anti-HBc), e-antigen (anti-HBe), and hepatitis A virus (anti-HAV), by radioimmunoassay (RIA). HBsAg was found in only two of the 417 subjects studied. Anti-HBs was detected in 112 samples (26.8%), anti-HBc in 114 (27.3%) and anti-HBe in 31 samples (7.4%). Serologic evidence of a previous or present infection by hepatitis B virus (HBV) was found in 34.5% of the samples studied. Males showed a greater prevalence of anti-HBs and anti-HBc, while anti-HBe was more common in females; however, these differences were not significant. With regard to age, a significantly higher prevalence of anti-HBs (p less than 0.05), anti-HBc (p less than 0.025) and anti-HBe (p less than 0.025) was found in the older age groups. Anti-HAV antibodies were present in 90% of the subjects studied, with no variation between the sexes. The anti-HAV rate in the group under 20 years was similar to that found in the older age groups. The total infection rate of hepatitis B virus in the Seychelles is lower than in other tropical areas, HBs antigen/antibody ratio approaching that in temperate areas. Elucidation of the reasons for the low prevalence of hepatitis B virus carriers among the Sevchelles population requires further investigation.