Hepatitis: Richardus JH

Idris BI, Brosa M, Richardus JH, Esteban R, Schalm SW, Buti M. · Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #18334876 No free full text.

Abstract: BACKGROUND: Chronic hepatitis B virus (HBV) infection can lead to fatal complications and death. Only a relatively small proportion of patients actually receive medication, and the majority requires long-term antiviral therapy that can result in the emergence of resistant strains of HBV. The study aimed to estimate the future burden of chronic hepatitis B in Spain over the next 20 years, the impact of current lamivudine treatment and the emergence of drug-resistant HBV. METHODS: We constructed a hypothetical cohort of people with active chronic HBV infection in Spain in 2005, and 'followed' the cohort for 20 years. The cohort was stratified with respect to factors that affect prognosis (i.e. hepatitis B e-antigen and histology-defined status). To estimate the burden, Markov mathematical simulation was performed based on three scenarios: natural history, treatment with antiviral drug (lamivudine) and treatment with a hypothetical drug with identical profiles to lamivudine but to which there is no resistance. RESULTS: We estimated that in 2005 there were around 111,000 individuals suffering from active chronic HBV infection. If the cohort is not treated, by the year 2025 there will be about 60,000 events of morbidity and 40,000 cases of liver-related deaths, with 1.84 billion euro expected to be consumed in providing care for the cohort. Treating 35% of the cohort with lamivudine will reduce the morbidity and mortality by 19 and 15%, respectively; whereas the hypothetical drug will reduce the morbidity and mortality by 27 and 24%. The cumulative cost savings resulting from the use of lamivudine and the hypothetical drug, respectively, are 160 and 300 million euro. Antiviral resistance accounts for a reduction of about one-third in the potential benefit of treatment, and almost a half of the potential cost saving. CONCLUSION: Chronic hepatitis B will pose a great burden in the future if the individuals with active disease are left untreated. Effective antiviral therapy and treatment coverage have substantial impact in reducing the future burden; however, antiviral resistance decreases treatment benefit considerably.

van Houdt R, Koedijk FD, Bruisten SM, Coul EL, Heijnen ML, Waldhober Q, Veldhuijzen IK, Richardus JH, Schutten M, van Doornum GJ, de Man RA, Hahné SJ, Coutinho RA, Boot HJ. · Public Health Service, Department of Infectious Diseases, Amsterdam, The Netherlands. · Vaccine. · Pubmed #19464531 No free full text.

Abstract: In November 2002, the Netherlands adopted a vaccination program targeted at behavioural risk groups. Between January 2003 and December 2007, 1386 patients acutely infected with HBV were reported. Reported cases declined from 326 in 2003 to 220 in 2007. Sexual intercourse was the most frequently reported mode of transmission (65%), especially among men having sex with men. Genotypes A and D remained predominant. In total, 40,600 participants were fully vaccinated, the overall compliance was 62%, and the estimated overall program coverage was 12% of the at-risk population. With more effort, more susceptibles may be reached, but the program will not be sufficient to substantially reduce HBV in the Netherlands. Therefore, universal vaccination should be considered.

Veldhuijzen IK, Mes TH, Mostert MC, Niesters HG, Pas SD, Voermans J, de Man RA, Götz HM, van Doornum GJ, Richardus JH. · Division of Infectious Disease Control, Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, The Netherlands. · J Med Virol. · Pubmed #19152416 No free full text.

Abstract: The transmission of infectious diseases can be traced using epidemiological and molecular information. In the current study, the congruence was assessed between sequence data of the hepatitis B virus (HBV) and epidemiological information resulting from source and contact tracing of patients seen at the Municipal Public Health Service in Rotterdam between 2002 and 2005. HBV genotypes A-G were present in 62 acute and 334 chronic HBV patients. At the sequence level, the identical sequences of members of epidemiological transmission pairs and the rarity of such pairs provided strong support for correctness of the hypothesized transmission routes. The molecular support for epidemiological transmission pairs derived from source and contact tracing was further assessed by using topological constraints in parsimony analyses in agreement with epidemiological information, and by taking the presence of polymorphic sites of HBV within patients into account. This, in principle, allows mutations in epidemiological clusters. Of 22 epidemiological clusters, six could be refuted, four clusters received support from the molecular analysis, and support for the remaining twelve clusters was ambiguous. Two of the four epidemiological pairs that received molecular support had diverged (by 3 and 15 mutations). These results show that levels of divergence cannot be used simply as an indicator of the likelihood that groups of sequences constitute transmission pairs. Instead, to confirm or refute transmission pairs, it is necessary to assess the likelihood of a common origin of HBV variants in epidemiologically defined transmission groups relative to the HBV diversity in the local community.

Koedijk FD, van Houdt R, Op de Coul EL, Dukers NH, Niesters HG, Mostert MC, Richardus JH, de Man RA, van Doornum GJ, van den Hoek JA, van de Laar MJ, Coutinho RA, Bruisten SM, Boot HJ. · Rijksinstituut voor Volksgezondheid en Milieu, Postbus 1, 3720 BA Bilthoven. · Ned Tijdschr Geneeskd. · Pubmed #19137968 No free full text.

Abstract: 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.

Veldhuijzen IK, van Driel HF, Vos D, de Zwart O, van Doornum GJ, de Man RA, Richardus JH. · Division of Infectious Disease Control, Municipal Public Health Service Rotterdam-Rijnmond, Rotterdam, the Netherlands. · Int J Infect Dis. · Pubmed #18678518 No free full text.

Abstract: OBJECTIVES: The prevalence of viral hepatitis varies worldwide. Although the prevalence of hepatitis A virus (HAV) and hepatitis B virus (HBV) infection is generally low in Western countries, pockets of higher prevalence may exist in areas with large immigrant populations. The aim of this study was to obtain further information on the prevalence of viral hepatitis in a multi-ethnic area in the Netherlands. METHODS: We conducted a community-based study in a multi-ethnic neighborhood in the city of Rotterdam, the Netherlands, including both native Dutch and migrant participants, who were tested for serological markers of hepatitis A, hepatitis B, and hepatitis C infection. RESULTS: Markers for hepatitis A infection were present in 68% of participants. The prevalence of hepatitis B core antibodies (anti-HBc), a marker for previous or current infection, was 20% (58/284). Prevalence of hepatitis A and B varied by age group and ethnicity. Two respondents (0.7%) had chronic HBV infection. The prevalence of hepatitis C was 1.1% (3/271). High levels of isolated anti-HBc were found. CONCLUSIONS: We found a high prevalence of (previous) viral hepatitis infections. This confirms previous observations in ethnic subgroups from a national general population study and illustrates the high burden of viral hepatitis in areas with large immigrant populations.

Veldhuijzen IK, Mostert MC, Niesters HG, Richardus JH, de Man RA. · GGD Rotterdam-Rijnmond, Cluster Infectieziektebestrijding, Postbus 70.032, 3000 LP Rotterdam. · Ned Tijdschr Geneeskd. · Pubmed #18624006 No free full text.

Abstract: OBJECTIVE: To assess the usefulness of a simple practical guideline based on hepatitis B e-antigen (HBeAg) status and a single alanine aminotransferase (ALT) determination to predict hepatitis B virus (HBV) load in chronic HBV patients as a criterion for referral to a specialist for possible antiviral therapy. DESIGN: Prospective observational study. METHOD: 420 patients with chronic HBV infection were seen at the Municipal Health Service (MHS) in Rotterdam between 2002 and 2005. The usefulness ofa guideline based on HBeAg positivity and/or elevated ALT levels to predict high HBV DNA levels (defined as more than 10(5) copies/ml) was determined. Patients with HBeAg or an elevated ALT level were referred to a specialist according to the practical guideline. Positive and negative predictive value, sensitivity, and specificity of the referral guideline for a high HBV-DNA level were calculated. RESULTS: Less than half, 43% (181/420) of the patients, were eligible for referral to specialist care. The positive predictive value of the referral guideline was 45% (82/181, 95% CI: 38-53). The negative predictive value, i.e. the proportion of patients with low viral loads who were (rightly) not selected for referral, was 95% (227/239; 95% CI: 71-97). The sensitivity was 87% (95% CI: 80-93): the patients selected included 82 of 94 patients with a high HBV DNA level. Of the 12 patients with high viral loads not referred according to the guideline, 11 had a viral load of between 10(5)-10(6) copies/ml. CONCLUSION: A referral guideline based on HBeAg status and a single ALT determination can successfully predict viral load in chronic HBV patients and can be used in primary care to select patients for referral to specialist care. This guideline may limit the number of unnecessarily referred patients, enhancing the efficiency of the care for patients with chronic HBV infection.

Toy M, Veldhuijzen IK, Mostert MC, de Man RA, Richardus JH. · Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands. · J Med Virol. · Pubmed #18205235 No free full text.

Abstract: The Netherlands is a low endemic country for hepatitis B virus (HBV). Rotterdam, a city in The Netherlands harbors a large group of chronic hepatitis B (CHB) patients of which most are born abroad. The study included 464 consecutive CHB patients who were reported to the Municipal Public Health Service in Rotterdam from January 1, 2002 to September 15, 2005. The HBV genotypes, possible transmission routes of infection and travel history of CHB patients born in The Netherlands, were compared with those CHB patients living in The Netherlands but who were foreign-born, taking into account the ethnicity of the mother. Of the 464 patients with CHB infection, 14% were Dutch-born and 86% were foreign-born. The CHB patients in the Dutch-born group had genotypes A (35%), B (15%), C (11%), D (37%), and G (2%). In the foreign-born group, the distribution of genotypes was A (20%), B (15%), C (11%), D (40%), and E (15%). In the Dutch-born group, sexual transmission accounted for a larger proportion of infections (P < 0.0001) compared to the foreign-born group, whereas perinatal transmission is reported to be higher in the foreign-born group and in the Dutch-born group with a foreign mother. The genotypes of the chronic HBV strains determined corresponded well with the HBV genotypes expected from the countries of origin of the patients or their mothers. Genotypes A and D are predominant in CHB patients in The Netherlands.

van Houdt R, Bruisten SM, Koedijk FD, Dukers NH, Op de Coul EL, Mostert MC, Niesters HG, Richardus JH, de Man RA, van Doornum GJ, van den Hoek JA, Coutinho RA, van de Laar MJ, Boot HJ. · GGD Public Health Service, Department of Infectious Diseases, Amsterdam, The Netherlands. · J Med Virol. · Pubmed #17516528 No free full text.

Abstract: 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.

Vos D, Götz HM, Richardus JH. · Division of Infectious Disease Control, Rotterdam Public Health Service, Rotterdam, The Netherlands. · Am J Infect Control. · Pubmed #17097460 No free full text.

Abstract: To describe the characteristics of needlestick injuries occurring to health care workers outside the hospital, a new case report form was implemented and analyzed after 12 months. A total of 144 incidents were reported. Of the needlestick injuries in nursing assistants, 84% involved an insulin needle or pen. Thirty-five percent of all health care workers and 47% of the nursing assistants were not vaccinated against hepatitis B. Hepatitis B vaccination grade in health care workers outside the hospital should be improved, in particular among nursing assistants.

van der Eijk AA, Niesters HG, Hansen BE, Pas SD, Richardus JH, Mostert M, Janssen HL, Schalm SW, de Man RA. · Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Centre Rotterdam, The Netherlands. · Eur J Gastroenterol Hepatol. · Pubmed #16215428 No free full text.

Abstract: OBJECTIVES: Despite an abundance of epidemiological evidence for horizontal transmission of hepatitis B virus (HBV), the transmission route remains to be fully elucidated. In a new approach, we evaluated quantitative HBV DNA content in serum, saliva and urine as a first step in exploring possible modes of horizontal transmission. METHODS: In an outpatient setting of an academic hospital, paired serum, saliva and urine samples were collected from 150 chronically infected HBV patients. A validated HBV DNA TaqMan assay was used to quantitatively measure HBV DNA. RESULTS: Mean log HBV DNA in serum was 5.8 (range, undetectable to 10.0 log HBV DNA) copies/ml, 50% of the patients had an HBV DNA above 10 copies/ml in serum. Mean log HBV DNA level in saliva was 3.2 (range, undetectable to 7.5) copies/ml, 15% had an HBV DNA above 10 copies/ml in saliva. Mean log HBV DNA level in urine was 2.6 (range, undetectable to 5.4) copies/ml and 1% had an HBV DNA above 10 copies/ml in urine. A high, non-linear correlation was shown between HBV DNA in serum and saliva (Spearman's rho 0.82) and between serum and urine (Spearman's rho 0.74). CONCLUSIONS: The significant amounts of HBV DNA found in saliva and urine in chronic HBV patients with high viraemia in serum may have implications for the understanding of hepatitis B epidemiology. The potential infectivity of these body fluids may provide an explanation for the 20% of cases of infection obtained through horizontal transmission for which the origin of infection is yet unknown.

Mostert MC, Richardus JH, de Man RA. · Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. · J Hepatol. · Pubmed #15582137 No free full text.

Abstract: BACKGROUND/AIMS: To evaluate a guideline selecting patients at the primary care level for referral to a specialist, to identify bottlenecks and subsequently implement and evaluate improvements. METHODS: Retrospective patient files analysis and a prospective cohort study. The study was conducted in Municipal Public Health Service (PHS), University Medical Center. Patients diagnosed with chronic hepatitis B virus (HBV) infection were referred to the PHS. Improvement of bottlenecks were identified in the referral chain, based on the guideline. Number of patients receiving correct advice, number of patients reaching the hospital for specialist care, time between notification of the PHS and final arrival in the hospital. RESULTS: The guideline for the referral of chronic HBV patients appeared to be appropriate, although one-third of the selected patients was not seen by the specialist. After the intervention more HBV patients (76 versus 61%) received correct advice from the PHS, and the number of HBV patients seen by the specialist increased by 18%. CONCLUSIONS: The referral guideline works, yet we could improve the efficiency of the guideline increasing the proportion of eligible patients reaching specialist care. In countries where mandatory reporting of HBV infections exists this guideline can be adapted to local health systems.

Richardus JH, Vos D, Veldhuijzen IK, Groen J. · Department of Infectious Diseases, Municipal Health Service, Rotterdam, The Netherlands. · J Med Virol. · Pubmed #14695660 No free full text.

Abstract: Seasonal fluctuations in hepatitis A have been observed in the Netherlands related to Turkish and Moroccan children after visiting their home countries. This study determined the prevalence and associated factors of hepatitis A virus (HAV) antibodies in Turkish and Moroccan children in Rotterdam. A random sample was taken of children in Rotterdam, aged 5-16 years, of Turkish and Moroccan origin, together with a random sample of native Dutch children aged 5-7 and 14-16 years. Blood was collected by finger prick on filter paper. IgG and IgM anti-HAV was detected by an enzyme-linked immunoassay (EIA). The 319 Turkish, 329 Moroccan, and 248 native Dutch children participated in the study. In Turkish children, IgG anti-HAV increased from 2.2% to 22.2% over the age groups. In Moroccan children, IgG anti-HAV increased from 10.2% to 57.7%. In native Dutch children, 0.8% had IgG anti-HAV in the youngest and 3.1% in the oldest age group. The percentage IgG-positive also having IgM anti-HAV was 21% in Turkish, and 41% in Moroccan children. No IgG-positive native Dutch children had IgM anti-HAV. The prevalence of IgG anti-HAV was associated with increased age, being Moroccan, longer stay in the country of origin before migrating to the Netherlands, and known contact to HAV. The majority of Turkish and Moroccan children aged 4-16 years in Rotterdam are not protected against HAV, but do have a high risk of becoming infected while visiting their native country. Active vaccination against HAV of these children is indicated, with as primary aim their own protection. Prevention of HAV-transmission in the general community should be seen as a secondary benefit. In addition, possible Dutch contacts of nonvaccinated Turkish and Moroccan children, such as day care workers and teachers, should also be vaccinated against HAV.

Mostert MC, Richardus JH, de Man RA. · Erasmus Medisch Centrum, afd. Maag-, Darm- en Leverziekten, Postbus 2040, 3000 CA Rotterdam. · Ned Tijdschr Geneeskd. · Pubmed #12635548 No free full text.

Abstract: OBJECTIVE: Evaluation of the Rotterdam guideline for referring patients with chronic hepatitis B virus (HBV) infections from primary to specialist care for diagnosis and treatment. DESIGN: Retrospective. METHOD: Whether or not the guideline was followed correctly was determined in patients with chronic hepatitis B who were reported to the Municipal Health Service (GGD) in Rotterdam in 1998 and 1999. This was done by a study of their files and by questioning their general practitioners by phone. RESULTS: During the study period, 376 cases of chronic hepatitis B were seen at the GGD; 32% of the patients dropped out during the referral trajectory. Drop-out took place at three different times: 13% during the process of deciding whether the patient should be referred according to the guideline, 12% during the consultation period at the GGD, and 7% after consultation at the GGD and before first contact with a specialist (via referral from the general practitioner). The reasons for dropping out were either procedural factors, such as missing information in the patient file and unclear management by the GGD, and personal factors such as failure of the general practitioner or the patient to comply with the recommendations. CONCLUSION: The guideline for the referral of chronic hepatitis B patients functioned well but implementation can be improved, since some patients did not reach the specialist. Improvement would be made possible by shortening the referral chain and by giving more information to patients and general practitioners about hepatitis B and its potential consequences.

Veldhuijzen IK, Mostert MC, Niesters HG, Richardus JH, de Man RA. · No affiliation provided · Gut. · Pubmed #17566039 No free full text.

This publication has no abstract.

Pars LL, Wolfers ME, de Zwart O, Brug J, de Man RA, Richardus JH. · No affiliation provided · Liver Int. · Pubmed #17498262 No free full text.

This publication has no abstract.