Secondary Prevention of Hepatitis B in the Netherlands

People with chronic hepatitis B virus infection remain infectious to others and are at risk of serious liver disease such as liver cirrhosis or liver cancer later in life. In the Netherlands, hepatitis B is low endemic and acute infections are mainly transmitted through sexual contact. Chronic infections are found mostly in migrants born in countries where hepatitis B is relatively prevalent. Primary prevention of hepatitis B is possible through vaccination, but vaccination does not have an impact on pre-existing chronic infections. Screening for hepatitis B is a form of secondary prevention, whereby antiviral treatment can be used to prevent the occurrence of hepatitis B related liver disease. As the possibilities of antiviral therapy to prevent liver disease caused by chronic hepatitis B have greatly improved, it becomes more important to identify chronic hepatitis B patients. In this thesis, the following research questions are addressed: 1) What are the! transmission routes, sources of infection and risk factors for acute hepatitis B virus infection in the Netherlands?; 2) What is the prevalence of hepatitis B virus infection in different ethnic groups in Rotterdam?; 3) What is the added value of molecular analysis in hepatitis B source and contact tracing?; 4) What is the impact of secondary prevention of hepatitis B? We conclude that to increase access to antiviral treatment for patients with active chronic hepatitis B, the detection of chronic hepatitis B patients should be improved. To do so, a proactive approach is necessary as most patients do not have symptoms

Limited access to hepatitis B/C treatment among vulnerable risk populations

Background: To investigate access to treatment for chronic hepatitis B/C among six vulnerable patient/population groups at-risk of infection: undocumented migrants, asylum seekers, people without health insurance, people with state insurance, people who inject drugs (PWID) and people abusing alcohol. Methods: An online survey among experts in gastroenterology, hepatology and infectious diseases in 2012 in six EU countries: Germany, Hungary, Italy, the Netherlands, Spain and the UK. A four-point ordinal scale measured access to treatment (no, some, significant or complete restriction). Results: From 235 recipients, 64 responses were received (27%). Differences in access between and within countries were reported for all groups except people with state insurance. Most professionals, other than in Spain and Hungary, reported no or few restrictions for PWID. Significant/complete treatment restriction was reported for all groups by the majority in Hungary and Spain, while Italian respondents reported no/few restrictions. Significant/complete restriction was reported for undocumented migrants and people without health insurance in the UK and Spain. Opinion about undocumented migrants in Germany and the Netherlands was divergent. Conclusions: Although effective chronic hepatitis B/C treatment exists, limited access among vulnerable patient populations was seen in all study countries. Discordance of opinion about restrictions within countries is seen, especially for groups for whom the health care system determines treatment access, such as undocumented migrants, asylum seekers and people without health insurance. This suggests low awareness, or lack, of entitlement guidance among clinicians. Expanding treatment access among risk groups will contribute to reducing chronic viral hepatitis-associated avoidable morbidity and mortality

Language support for linguistic minority chronic hepatitis B/C patients: an exploratory study of availability and clinicians’ perceptions of language barriers in six European countries

Background: Language support for linguistic minorities can improve patient safety, clinical outcomes and the quality of health care. Most chronic hepatitis B/C infections in Europe are detected among people born in endemic countries mostly in Africa, Asia and Central/Eastern Europe, groups that may experience language barriers when accessing health care services in their host countries. We investigated availability of interpreters and translated materials for linguistic minority hepatitis B/C patients. We also investigated clinicians’ agreement that language barriers are explanations of three scenarios: the low screening uptake of hepatitis B/C screening, the lack of screening in primary care, and why cases do not reach specialist care. Methods: An online survey was developed, translated and sent to experts in five health care services involved in screening or treating viral hepatitis in six European countries: Germany, Hungary, Italy, the Netherlands, Spain and the United Kingdom (UK). The five areas of health care were: general practice/family medicine, antenatal care, health care for asylum seekers, sexual health and specialist secondary care. We measured availability using a three-point ordinal scale (‘very common’, ‘variable or not routine’ and ‘rarely or never’). We measured agreement using a five-point Likert scale. Results: We received 238 responses (23% response rate, N = 1026) from representatives in each health care field in each country. Interpreters are common in the UK, the Netherlands and Spain but variable or rare in Germany, Hungary and Italy. Translated materials are rarely/never available in Hungary, Italy and Spain but commonly or variably available in the Netherlands, Germany and the UK. Differing levels of agreement that language barriers explain the three scenarios are seen across the countries. Professionals in countries with most infrequent availability (Hungary and Italy) disagree strongest that language barriers are explanations. Conclusions: Our findings show pronounced differences between countries in availability of interpreters, differences that mirror socio-cultural value systems of ‘difference-sensitive’ and ‘difference-blindness’. Improved language support is needed given the complex natural history of hepatitis B/C, the recognised barriers to screening and care, and the large undiagnosed burden among (potentially) linguistic minority migrant groups

Estimating the scale of chronic hepatitis B virus infection among migrants in EU/EEA countries

Background: Chronic hepatitis B (CHB) related morbidity and mortality can be reduced through risk group screening, linkage to care and anti-viral treatment. This study estimates the number of CHB cases among foreign-born (migrants) in the European Union and European Economic Area (EU/EEA) countries in order to identify the most affected migrant populations. Methods: The CHB burden was estimated by combining: demographic data on migrant population size by country of birth in the EU/EEA, extracted from European statistical databases; and CHB prevalence in migrants' countries of birth and in EU/EEA countries, derived from a systematic literature search. The relative contribution of migrants from endemic countries to the total CHB burden in each country was also estimated. The reliability of using country of birth prevalence as a proxy for prevalence among migrants was assessed by comparing it to the prevalence found in studies among migrants in Europe. Results: An estimated 1-1.9 million CHB-infected migrants from endemic countries (prevalence ≥2%) reside in the EU/EEA. Migrants from endemic countries comprise 10.3% of the total EU/EEA population but account for 25% (15%-35%) of all CHB cases. Migrants born in China and Romania contribute the largest number of infections, with over 100,000 estimated CHB cases each, followed by migrants from Turkey, Albania and Russia, in descending order, with over 50,000 estimated CHB cases each. The CHB prevalence reported in studies among migrants in EU/EEA countries was lower than the country of birth prevalence in 9 of 14 studies. Conclusions: Migrants from endemic countries are disproportionately affected by CHB; their contribution however varies between EU/EEA countries. Migrant focused screening strategies would be most effective in countries with a high relative contribution of migrants and a low general population prevalence. In countries with a higher general population prevalence and a lower relative contribution of migrants, screening specific birth cohorts may be a more effective use of scarce resources. Quantifying the number of CHB infections among 50 different migrant groups residing in each of the 31 EU/EEA host countries helps to identify the most affected migrant communities who would benefit from targeted screening and linkage to care

Estimating the scale of chronic hepatitis C virus infection in the EU/EEA: A focus on migrants from anti-HCV endemic countries

Background: Increasing the proportion diagnosed with and on treatment for chronic hepatitis C (CHC) is key to the elimination of hepatitis C in Europe. This study contributes to secondary prevention planning in the European Union/European Economic Area (EU/EEA) by estimating the number of CHC (anti-HCV positive and viraemic) cases among migrants living in the EU/EEA and born in endemic countries, defining the most affected migrant populations, and assessing whether country of birth prevalence is a reliable proxy for migrant prevalence. Methods: Migrant country of birth and population size extracted from statistical databases and anti-HCV prevalence in countries of birth and in EU/EEA countries derived from a systematic literature search were used to estimate caseload among and most affected migrants. Reliability of country of birth prevalence as a proxy for migrant prevalence was assessed via a systematic literature search. Results: Approximately 11% of the EU/EEA adult population is foreign-born, 79% of whom were born in endemic (anti-HCV prevalence ≥1%) countries. Anti-HCV/CHC prevalence in migrants from endemic countries residing in the EU/EEA is estimated at 2.3%/1.6%, corresponding to ~580,000 CHC infections or 14% of the CHC disease burden in the EU/EEA. The highest number of cases is found among migrants from Romania and Russia (50-60,000 cases each) and migrants from Italy, Morocco, Pakistan, Poland and Ukraine (25-35,000 cases each). Ten studies reporting prevalence in migrants in Europe were identified; in seven of these estimates, prevalence was comparable with the country of birth prevalence and in three estimates it was lower. Discussion: Migrants are disproportionately affected by CHC, account for a considerable number of CHC infections in EU/EEA countries, and are an important population for targeted case finding and treatment. Limited data suggest that country of birth prevalence can be used as a proxy for the prevalence in migrants

Point-of-Care Tests for Hepatitis B Are Associated with A Higher Linkage to Care and Lower Cost Compared to Venepuncture Sampling During Outreach Screenings in an Asian Migrant Population

Background: This study compares venepuncture versus point-of-care (POC) HBsAg tests on screening cost and linkage to care in prospective outreach screenings in an Asian population in three major cities in Belgium between 10/2014 and 5/2018. Methods: Two community outreach screening programs were organised between 10/2014 and 5/2018. The first screening program used venepuncture and serologic testing for HBsAg. In the second program, HBsAg was tested in finger stick blood POC tests. Positive results were confirmed during outpatient visits with serologic testing. Linkage to care was defined as having received specialist care follow-up with at least one abdominal ultrasound within three months of screening. Results: For 575 participating individuals, 571 valid results were obtained, 456 with venepuncture, and 115 using POC testing. Overall HBsAg seroprevalence was 6.8%. Linkage to care was higher when using POC testing compared to venepuncture (86% or n = 6/7 versus 34% or n = 11/32; p = 0.020). The POC screening program was economically more attractive with a total cost of € 1,461.8 or € 12.7 per person screened compared to € 24,819 or € 54.0 per person screened when using venepuncture testing. Results and an appointment for specialist care follow-up were given onsite with POC testing, while with venepuncture testing; results were sent within 20-45 days. Conclusion: In an Asian migrant population in Belgium with an HBsAg seroprevalence of 6.8%, HBV screening based on POC tests resulted in lower costs per person screened (76.5% lower), and higher linkage to care (2.5 times)

Additional evidence on serological correlates of protection against measles: An observational cohort study among once vaccinated children exposed to measles

To assess correlates of protection against measles and against subclinical measles virus (MV) infection, we recruited once-vaccinated children from geographic regions associated with increased MV circulation and/or at schools with low vaccination coverage in the Netherlands. Paired blood samples were collected shortly after onset of the measles outbreak and after the outbreak. A questionnaire was used to document the likelihood of exposure to MV and occurrence of measles-like symptoms. All blood samples were tested for MV-specific antibodies with five different assays. Correlates of protection were assessed by considering the lowest neutralizing antibody levels in children without MV infection, and by ROC analyses. Among 91 participants, two seronegative children (2%) developed measles, and an additional 19 (23%) experienced subclinical MV infection. The correlate of protection against measles was lower than 0.345 IU/mL. We observed a decreasing attack rate of subclinical MV infection with increasing levels of specific antibodies until 2.1 IU/mL, above which no subclinical MV infections were detected. The ROC analyses found a correlate of protection of 1.71 IU/mL (95% CI 1.01–2.11) for subclinical MV infection. Our correlates of protection were consistent with previous estimates. This information supports the analyses of serosurveys to detect immunity gaps that require targeted intervention strategies

The role of the general practitioner in the screening and clinical management of chronic viral hepatitis in six EU countries

Introduction. Chronic viral hepatitis is still a major public health concern in the EU. In order to halt the progression of the disease and to prevent onward transmission, timely recognition and accurate clinical management are crucial. The aim of the present study was to investigate the role of the general practitioner (GP) in the screening of persons at risk and in the clinical management of chronic viral hepatitis patients in six EU countries. Methods. An online survey among GPs and secondary-care specialists was conducted in the UK, Germany, the Netherlands, Hungary, Italy and Spain. In the GP survey, we used a four-point Likert scale to find out how commonly risk groups are screened. In both surveys, we measured GPs involvement in monitoring clinical indicators in patients undergoing antiviral treatment, and explored whether patients in four clinical scenarios are referred back to primary care. Results. Between five and 10 experts per professional group were surveyed, except for Spain (GPs: n = 2; Specialists: n = 4) and, in the case of the GP survey, Hungary (GPs: n = 1) and Germany (GPs: n = 4). Migrants are variably or not routinely screened for hepatitis B/C in the majority of cases. The majority of GPs reported that hepatitis B/C screening was routinely offered to people who inject drugs. In Hungary, Italy and in the Netherlands, screening sex workers is not a regular practice. As to whether GPs offer screening to men who have sex with men, responses varied; in Germany, the Netherlands and Italy, screening was "variably" or "commonly" implemented, while in Hungary the practice seems to be sporadic. In the UK, screening for hepatitis B seems to be common practice among GPs, while hepatitis C testing is only occasionally offered to this risk group. Most GPs (> 44%) in all countries except Hungary reported that hepatitis B/C screening was very commonly offered to HIV patients. The role of GPs in monitoring hepatitis cases and the referral of cases back to GPs by specialists varied both within and between countries. GPs are unlikely to monitor clinical outcomes other than side effects in patients undergoing treatment. Patients who have had a sustained virological response are usually referred back to GPs, whereas patients undergoing antiviral treatment and those who do not respond to treatment are rarely referred back. Conclusions. The GP's decision to offer screening to risk groups often seems to be an individual choice of the healthcare professional. Raising GPs' awareness of the disease, for example through the adoption of effective strategies for the dissemination and implementation of the existing guidelines for general practice, is strongly needed. The role of GPs and specialists involved in the management of chronically infected patients should also be clarified, as opinions sometimes differ markedly even within each professional group

Een geschiedenis van de Nederlandse predikant

This systematic review aimed at estimating chronic hepatitis B (HBV) and C virus (HCV) prevalence in the European Union (EU) and Economic Area (EEA) countries in the general population, blood donors and pregnant women