Historic and current hepatitis B viral DNA and quantitative HBsAg level are not associated with cirrhosis in non-Asian women with chronic hepatitis B.

BACKGROUND: Some studies done in Asian patients have shown that serum levels of hepatitis B virus (HBV) DNA predict the development of cirrhosis. However, it is unclear whether this also applies for non-Asian patients. This study investigated historic and current HBV DNA and quantitative hepatitis B surface antigen (HBsAg) levels as predictors of cirrhosis in non-Asian women with chronic HBV. METHODS: A retrospective cohort study of non-Asian women with chronic HBV was performed. Among other variables, HBV DNA and quantitative HBsAg levels were measured in stored historic serum samples obtained during pregnancy (period 1990-2004) and current serum samples (period 2011-2012) to determine any association with liver cirrhosis by liver stiffness measurement (LSM). RESULTS: One hundred and nineteen asymptomatic, treatment-naïve non-Asian women were included; the median number of years between the historic sample and the current sample was 17 (interquartile range (IQR) 13-20). The median historic log HBV DNA and quantitative log HBsAg levels were 2.5 (IQR 1.9-3.4) IU/ml and 4.2 (IQR 3.6-4.5) IU/ml, respectively. LSM diagnosed 14 patients (12%) with F3-F4 fibrosis, i.e. stiffness >8.1kPa. No association of cirrhosis was found with historic HBV DNA (relative risk (RR) 0.34, 95% confidence interval (CI) 0.05-2.44) or with the quantitative HBsAg level (HBsAg level >1000 IU/ml, RR 0.35, 95% CI 0.11-1.11). Multivariable analysis identified alcohol consumption (odds ratio (OR) 6.4, 95% CI 1.3-30.1), aspartate aminotransferase >0.5 times the upper limit of normal (OR 15.4, 95% CI 1.9-122.6), and prothrombin time (OR 12.0, 95% CI 1.2-120.4), but not HBV DNA or quantitative HBsAg level, to be independent predictors of the presence of cirrhosis. CONCLUSIONS: Neither historic nor current HBV DNA or the quantitative HBsAg level is associated with the development of HBV-related cirrhosis in non-Asian women.

ELF-test less accurately identifies liver cirrhosis diagnosed by liver stiffness measurement in non-Asian women with chronic hepatitis B.

BACKGROUND: The enhanced liver fibrosis test (ELF-test) has been validated for several hepatic diseases. However, its performance in chronic hepatitis B virus (CHB) infected patients is uncertain. OBJECTIVE: This study investigates the diagnostic value of the ELF test for cirrhosis identified by liver stiffness measurement (LSM) in non-Asian women with CHB. STUDY DESIGN: Women of non-Asian origin with perinatally acquired CHB infection, detected during pregnancy in the period 1990-2003, returned to our center between September 2011 and May 2012 for LSM and blood sampling to perform an ELF test and to calculate, APRI and FIB-4 scores. Fibrosis stages were classified by the METAVIR system. RESULTS: A total of 119 women were included in this study with a median age of 43 years, all ALT levels being <2× ULN and all being HBeAg negative. The overall median LSM (IQR) stiffness and ELF test were 5.5kPa (4.0-6.8) and 8.4 (7.8-9.2) respectively. LSM and ELF test classified 14 (12%) and 19 (16%) patients with severe fibrosis to cirrhosis (≥F3, i.e. liver stiffness >8.1kPa), however in only 4 (3%) patients there was an agreement between LSM and ELF test. With LSM as reference, the area under receiver operating characteristic curve (AUROC) for detection of ≥F3 fibrosis was for ELF 0.65 (95% CI 0.51-0.80; p=0.06), APRI 0.66 (0.50-0.82; p=0.07) and FIB-4 0.66 (0.49-0.82; p=0.07). CONCLUSION: The ELF test less accurately discriminates severe fibrosis or cirrhosis when compared to LSM in our cohort of non-Asian women with CHB.

Population-based study on the seroprevalence of parvovirus B19 in Amsterdam.

A study was undertaken to estimate the seroprevalence of parvovirus B19 infection in the general adult population of Amsterdam, The Netherlands. To our knowledge this is the first study testing parvovirus B19 in a random sample of the Dutch adult population. The study was a cross-sectional survey, and the study sample was stratified by age and ethnicity, with deliberate oversampling of minority ethnic groups. Serum samples obtained from 1,323 residents in 2004 were tested for antibodies to parvovirus B19. Basic demographic data (gender, age, country of birth, and number of children) were also available. Sixty-two percent of the participants were seropositive; corrected for the oversampling the estimated prevalence in the Amsterdam adult population was 61%. No specific predictors or risk groups for seropositivity were identified. In our urban adult study population no positive correlation with increasing neither age, nor significant differences between age groups were found. These results imply that almost 40% of the adult Amsterdam population is susceptible to infection. J. Med. Virol. 81:1305-1309, 2009. (c) 2009 Wiley-Liss, Inc.

Significance of isolated antibody to hepatitis B core antigen in Dutch national vaccination campaign of behavioural high-risk groups.

In the Dutch national vaccination campaign for behavioural risk groups, anti-HBcore is used as the primary HBV screening test. Samples with positive results undergo testing for active infection (HBsAg) but are otherwise accepted as indicating past infection, thereby assuming immunity. This study evaluated evidence for immunity in the target population screened on the basis of this algorithm, by re-analysing 1000 anti-HBcore-positive blood samples equally divided among risk groups: 14.7% of confirmed anti-HBcore lacked anti-HBs ('isolated' anti-HBcore). Independent risk factors for isolated anti-HBcore were risk group, HCV infection in hard-drug users (DU) and origin from Sub-Saharan Africa. After extrapolation, the proportion of participants who were said to be immune but lacked any additional evidence of immunity amounted to 9.6% (ranging from 12.5% in DU to 6.5% in men who have sex with men). It is recommended that as a minimum anti-HBs screening is included in testing algorithms used to determine vaccination programmes for risk groups, in particular in DU.

Cost-effectiveness estimates for antenatal HIV testing in the Netherlands.

This paper provides an estimation of the lifetime health-care cost of HIV-infected children and an update of the cost-effectiveness of universal HIV-screening of pregnant women in Amsterdam (The Netherlands). During 2003-2005, we collected data concerning the prevalence of newly diagnosed HIV-infected pregnant women in Amsterdam. Also, data on resource utilization and HAART regimen for HIV-infected children was gathered from a national registry. Using Kaplan-Meier survival analysis, we estimated the life-expectancy of a vertically HIV-infected child at 19 years, with the corresponding lifetime health-care costs of 179,974 Euros. HIV-screening of pregnant women could prevent 2.4 HIV transmissions annually in Amsterdam, based on an estimated prevalence of nine yet undiagnosed HIV-positive pregnant women per 10,000 pregnancies. We show that universal HIV screening during pregnancy generates significant net cost savings and health benefits in most situations. Universal antenatal HIV screening is justified in Amsterdam from a health-economic point of view.

[Hepatitis B virus transmission patterns in the Netherlands, 2004]. / Transmissiepatronen van hepatitis B-virus in Nederland, 2004.

OBJECTIVE: To gain insight into hepatitis B virus (HBV) transmission in the Netherlands. DESIGN: Descriptive. METHOD: During 2004, epidemiological data and blood samples (if available) were collected for all reported cases of acute HBV infections in the Netherlands. Following DNA isolation and amplification a 648 base pairs fragment of the HBV S gene was sequenced and subjected to phylogenetic analysis. The sequencing details were also linked to epidemiological information. RESULTS: In 2004, 291 cases ofacute HBV infections were reported. Blood samples were received from 171 patients (59%), and the genotype could be determined for 158 patients (54%). 6 genotypes were identified: A (64%), B (3%), C (3%), D (21%), E (5%) and F (4%). Of all patients with genotype A, 52% had been infected via homosexual or bisexual contact and 16% via heterosexual contact. Of all patients with genotype D, 42% had been infected via heterosexual contact and 15% via homosexual or bisexual contact. The genotype A cluster was extremely homogeneous with many identical sequences, while genotype B-E clusters were more heterogeneous. 4 identical sequences were found within genotype F, but the patients could not be epidemiologically linked. CONCLUSION: Sexual transmission, particularly via homosexual or bisexual contact in men, formed the most important risk factor for acquiring an acute HBV infection. Genotype A was predominant in the Netherlands, especially among homosexual or bisexual men. Most infections within genotype D occurred as a result of heterosexual contact. The results show that there was ongoing transmission of HBV in homosexual or bisexual men, while in heterosexuals more cases of new introduction were seen, possibly via chronic carriers from areas where HBV is endemic.

Population-based study on the seroprevalence of hepatitis A, B, and C virus infection in Amsterdam, 2004.

In order to enhance screening and preventive strategies, this study investigated the seroprevalence of hepatitis A, B, and C in the general adult urban population and in subgroups. In 2004, sera from 1,364 adult residents of Amsterdam were tested for viral markers. Sociodemographic characteristics were collected using a standardized questionnaire. For hepatitis A, 57.0% was immune. Of first-generation immigrants from Turkey and Morocco, 100% was immune. Of all Western persons and second-generation non-Western immigrants, approximately half was still susceptible. For hepatitis B, 9.9% had antibodies to hepatitis B core antigen (anti-HBc) and 0.4% had hepatitis B surface antigen. Anti-HBc seroprevalences were highest among first-generation immigrants from Surinam, Morocco, and Turkey, and correlated with age at the time of immigration, and among men with a sexual preference for men. Seroprevalence among second-generation immigrants was comparable to Western persons. The seroprevalence of hepatitis C virus antibodies was 0.6%. In conclusion, a country with overall low endemicity for viral hepatitis can show higher endemicity in urban regions, indicating the need for differentiated regional studies and prevention strategies. More prevention efforts in cities like Amsterdam are warranted, particularly for hepatitis A and B among second-generation immigrants, for hepatitis B among men with a sexual preference for men, and for hepatitis C. Active case finding strategies are needed for both hepatitis B and C.

Molecular epidemiology of acute hepatitis B in the Netherlands in 2004: nationwide survey.

To gain insight into hepatitis B virus (HBV) transmission in the Netherlands, epidemiological data and sera were collected from reported cases of acute HBV infections in the Netherlands in 2004. Cases were classified according to mode of transmission. A fragment of the S-gene of HBV (648 bp) was amplified, sequenced, and subjected to phylogenetic analysis. Of the 291 acute HBV cases reported in 2004, 158 (54%) were available for genotyping. Phylogenetic analysis identified 6 genotypes: A (64%), B (3%), C (3%), D (21%), E (5%) and F (5%). Of HBV infected men having sex with men, 86% were infected with genotype A, accounting for 43% of all patients infected with this genotype. There were only three reported cases of injecting drug use of which one was available for sequencing (genotype A). Unlike the genotype A cluster, sequences within the genotype B-E clusters were heterogenic. Within genotype F, several isolates had identical sequences, but patients could not be epidemiologically linked. Sexual transmission, particularly by men having sex with men was the most important transmission route for HBV. Injecting drug use plays a minor role. Genotype A is predominant in the Netherlands, especially among men having sex with men. In addition to imported strains, there seems to be a pool of related but non-identical strains circulating among chronic carriers in the migrant population, from which occasionally new patients are infected, primarily by heterosexual transmission.

[The molecular epidemiology of hepatitis A in The Netherlands; the usefulness of typing isolated viral strains]. / Moleculaire epidemiologie van hepatitis A in Nederland; het nut van het typeren van geïsoleerde virusstammen.

OBJECTIVE: To investigate the epidemiological links between several outbreaks of hepatitis A in The Netherlands (2001-2004). DESIGN: Descriptive. METHOD: Blood samples taken in connection with reports of hepatitis A to municipal health centres from 2001-2004, were typed by determining the nucleotide sequence of the VP3-VP1 and the VP1-P2A regions of the genome of the hepatitis A virus (HAV). Genetic distances were represented graphically by means of a phylogenetic tree. RESULTS: The study into the spread of various subtypes of HAV showed a clear link between the HAV-(sub)genotype and risk of transmission: in men that have sex with men only genotype 1A occurred, in travellers to African countries genotype 1B was predominantly seen. CONCLUSION: A database containing various viral strains from people with hepatitis A in The Netherlands could, if kept up to date, be used as an aid in confirming the classical way of tracing sources as well as for the evaluation of preventative measures.

[Legionella outbreak in Amsterdam: a cooling tower as the source]. / Legionella-uitbraak in Amsterdam: koeltoren als bron.

During the period 6-28 July 2006, 30 confirmed cases of Legionella infection were identified in Amsterdam, 2 of which were fatal. All had a positive urinary antigen test, by which Legionella pneumophila serogroup I could be demonstrated. Consultations between the parties involved in the control of infectious diseases started on July 7th, as soon as it became clear that there was an outbreak. On July 10th it was established that relatively many of these patients lived in the eastern part of the city centre. After a study of the prevailing winds during the past 3 weeks, the search for installations containing water was started. A cooling tower in the town centre was closed on July 11th by way of precaution. During the following week, this tower was proven to be the source of the outbreak.

Effectiveness of a hepatitis A vaccination program for migrant children in Amsterdam, The Netherlands (1992-2004).

OBJECTIVE: To evaluate the impact and effectiveness of risk-group vaccination against hepatitis A targeted at migrant children living in a country with low endemicity of hepatitis A. METHODS: Retrospective population based data analysis. Routinely collected data on hepatitis A incidence in migrant children and other risk groups in Amsterdam from 1 January 1992 to 2004 were analyzed and related to exposure, immunity and vaccination coverage in migrant children. RESULTS: The overall hepatitis A incidence in Amsterdam declined after a pediatric vaccine was introduced in 1997. This decline was seen in migrant children traveling to hepatitis A-endemic countries, contacts with hepatitis A patients, primary school students, injecting drug users, and persons with unknown source of infection, but not in men who have sex with men (MSM) or in travelers to endemic countries other than migrant children. CONCLUSION: The hepatitis A vaccination campaigns are effective: they reduce both import and secondary HAV cases. The campaigns could be more efficient and cost-effective if the hepatitis B vaccinations currently given to these groups were replaced by a combined hepatitis A and B vaccine. This would increase the hepatitis A vaccination coverage considerably and further reduce the hepatitis A incidence.

Tattooing, permanent makeup and piercing in Amsterdam; guidelines, legislation and monitoring.

Tattooing, body piercing and permanent makeup are increasing in popularity. Here, we describe the procedures involved in these practices, their risks, the content of guidelines developed by the Municipal Health Service in Amsterdam (the Netherlands) to reduce infection risks, the legislation in the city of Amsterdam, and results of monitoring in tattoo and piercing studios.

Additional value of typing Noroviruses in gastroenteritis outbreaks in Amsterdam, The Netherlands.

BACKGROUND: In Amsterdam, 17 of the 55 gastroenteritis (GI) outbreaks reported from January 2002 to May 2003 were confirmed to be caused by noroviruses (NV). OBJECTIVE: In this study, we describe the molecular epidemiology of a group of nine outbreaks associated with a catering firm and two outbreaks, 5 months apart, in an Amsterdam hospital. All outbreaks were typed to confirm their linkage, and the hospital-related cases were studied to see if the two outbreaks were caused by one persisting NV strain or by a reintroduction after 5 months. RESULTS AND CONCLUSIONS: For the outbreaks associated with the catering firm one NV genogroup I strain was found which was identical in sequence among customers and employees of the caterer. This was not the strain that predominantly circulated in 2002/2003 in and around Amsterdam, which was the NV genogroup II4 "new variant" (GgII4nv) strain. In the Amsterdam hospital, the two outbreaks were caused by this predominant GgII4nv type, and we argue that NV was most likely reintroduced in the second outbreak from the Amsterdam community.

Tattooing, permanent makeup and piercing in Amsterdam; guidelines, legislation and monitoring.

Tattooing, body piercing and permanent makeup are increasing in popularity. Here, we describe the procedures involved in these practices, their risks, the content of guidelines developed by the Municipal Health Service in Amsterdam (the Netherlands) to reduce infection risks, the legislation in the city of Amsterdam, and results of monitoring in tattoo and piercing studios.

Molecular epidemiology of hepatitis A in Noord-Brabant, The Netherlands.

BACKGROUND: Previous studies on the molecular epidemiology of hepatitis A virus (HAV) in Amsterdam, The Netherlands, show that subgenotype 1A is mainly seen among homosexual men practising anonymous oral-anal sex in saunas and darkrooms, while subgenotype 1B is usually detected among children originating from Morocco, and subgenotype 3A is mostly found among travellers to Pakistan. OBJECTIVE: We studied the genotype distribution in a more rural area of The Netherlands, Noord-Brabant, and compared it with Amsterdam. STUDY DESIGN: We collected blood and feces samples from 34 HAV IgM(+) individuals who were reported from August 2001-March 2003 at the Municipal Health Service (MHS) Heart for Brabant (Brabant). We also collected feces samples from nine household contacts of whom the HAV IgM status was not known. HAV RNA was isolated and subsequently amplified by reverse transcriptase polymerase chain reaction (RT-PCR) at the VP1-P2a and the VP3-VP1 region, sequenced and analysed. RESULTS AND CONCLUSIONS: In most cases, relations between risk groups and HAV subgenotypes in Noord-Brabant were similar to those in Amsterdam. Next to genotypes 1 and 3 we also detected a genotype 2/7 strain in a Noord-Brabant case. Also, in contrast to the Amsterdam study, sporadic transmission occurred among various risk groups. Children involved in a school-related outbreak were infected with strains identical to one that was previously isolated from a man who has sex with men (MSM). Also, Dutch patients having no epidemiological link with Turkish or Moroccan children harboured strains imported from high-endemic countries. Furthermore, we report a special case in which HAV may be causally involved in meningitis. The results of this study show that the molecular epidemiology of HAV in The Netherlands can be more complicated than previously anticipated and that HAV phylogenetic studies can provide important information for the design of appropriate public health measures.

[Less refusal to participate in HIV screening among pregnant women in the Amsterdam region since the introduction of standard HIV screening using the opting-out method]. / Minder weigering van deelname aan HIV-screening door zwangeren in Amsterdam sedert de invoering van de standaard-HIV-screening--tenzij weigering ('opting-out'-methode).

In 2003 the Municipal Health Service in Amsterdam started to screen pregnant women for HIV according to the opting-out method. In this method the HIV test is routinely included in the prenatal screening along with hepatitis B virus (HBV) and syphilis. If the woman does not want to be tested for HIV then she must actively opt out of this test. This screening method was chosen because in the universal screening method used in 2002, women had to give their explicit consent to test for HIV and this led to a high refusal rate (13.6%), especially among women from AIDS-endemic countries. After the introduction of the opting-out method, the refusal rate fell from 3% in the first quarter of 2003 to 1.4% in the last quarter of 2003. None of the women refused to be tested for HBV or syphilis. In 2003, the HIV prevalence among pregnant women was 0.3% (35/13.621). The experiences with this screening method in Amsterdam were used to implement the national opting-out method for HIV screening in pregnant women, which was introduced on 1 January 2004.

Pharmaco-economic evaluation of targeted hepatitis A vaccination for children of ethnic minorities in Amsterdam (The Netherlands).

OBJECTIVE: Estimate cost-effectiveness of vaccination against hepatitis A virus (HAV) for children of ethnic minorities in Amsterdam. BACKGROUND: Pharmaco-economic analysis is relevant for motivating reimbursement of vaccination costs in the framework of a programmatic approach to vaccination of ethnic minorities. DESIGN: Pharmaco-economic modeling. METHOD: In cost-effectiveness analysis, costs, benefits and health gains were estimated for a large-scale HAV-vaccination for children of Turkish and Maroccan origin. Analysis was performed from the societal perspective, as recommended in the Dutch guidelines for pharmaco-economic research. This implies that indirect costs of production losses are included in the analysis. Cost-effectiveness was expressed in net costs per adult HAV-infection averted in incremental and aggregate analysis. Incremental analysis compares targeted vaccination with the current limited-scale HAV-vaccination that exists, whereas aggregate analysis compares targeted vaccination with the sheer absence of vaccination. RESULTS: Net aggregate costs of targeted HAV-vaccination for Turkish and Maroccan children in Amsterdam amounts to 61.000. Cost-effectiveness was estimated, in aggregate and incremental analysis, at 13.500 and 11.100 respectively per adult HAV-infection averted. Uni- and multivariate sensitivity analyses show that major impact on cost-effectiveness may be expected from reductions in the vaccine price through economies of scale. Probabilistic sensitivity analysis indicates possible large fluctuations in cost-effectiveness from 1 year to another, related to varying incidence of disease. CONCLUSION: HAV-vaccination for children from ethnic minorities in Amsterdam is not cost saving, but may have a favourable cost-effectiveness. Such a vaccination program fits into the recent Dutch policy of specific vaccinations directed at groups of ethnic minorities, such as for hepatitis B.