Hepatitis: Schutten M

Schutten M. · Department of Virology, s-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. · Expert Rev Mol Diagn. · Pubmed #18598219 No free full text.

Abstract: The introduction of commercially available quantitative HIV-1 RNA detection methods at the end of the last century has had a significant impact on the management of patients requiring treatment. Similarly for hepatitis C virus (HCV), clinical decision-making with respect to initiation and prolonging therapy is largely based on data from viral load assays. The methods developed in the early 1990s and further improved since then still have significant drawbacks. For example, they are labor intensive, have a small dynamic range and are contamination sensitive. The development of real-time detection techniques for reverse transcription PCR has in part solved these problems. In the present review the advantages and disadvantages of the recently marketed Abbott Realtime HCV and HIV-1 viral load assays relative to their competitors will be discussed.

Schutten M, Niesters HG. · Department of Virology, University Hospital Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. · Expert Rev Mol Diagn. · Pubmed #11901810 No free full text.

Abstract: The possibility to detect viral DNA or RNA in a quantitative manner has already contributed significantly to the management and diagnosis of viral infections, as well as to the understanding of virus-host interactions. New developments in amplification techniques based on real-time detection, as well as automation of the whole process, will soon be introduced in a diagnostic laboratory setting, thereby enabling a rapid turnaround time to generate both quantitative and qualitative results. New guidelines for disease management, as well as extensive quality control and standardization programs must be introduced.

Buster EH, Flink HJ, Cakaloglu Y, Simon K, Trojan J, Tabak F, So TM, Feinman SV, Mach T, Akarca US, Schutten M, Tielemans W, van Vuuren AJ, Hansen BE, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · Gastroenterology. · Pubmed #18585385 No free full text.

Abstract: BACKGROUND & AIMS: The aim of this study was to evaluate the long-term sustainability of response in patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B treated with pegylated interferon (PEG-IFN) alpha-2b alone or in combination with lamivudine. METHODS: All 266 patients enrolled in the HBV99-01 study were offered participation in a long-term follow-up (LTFU) study. Patients were treated with PEG-IFN alpha-2b (100 mug/wk) alone or in combination with lamivudine (100 mg/day) for 52 weeks. Initial response was defined as HBeAg negativity at 26 weeks posttreatment. For the LTFU study, patients had one additional visit after the initial study (mean interval, 3.0 +/- 0.8 years). RESULTS: Of 266 patients enrolled in the initial study, 172 (65%) participated in the LTFU study. At LTFU, HBeAg and hepatitis B surface antigen (HBsAg) negativity were observed in 37% and 11% of 172 patients, respectively. Sixty-four patients were classified as initial responders and 108 as nonresponders. Among the initial responders, sustained HBeAg negativity and HBsAg loss were observed in 81% and 30%, respectively. Significantly higher rates of HBeAg negativity were observed in genotype A-infected initial responders compared with those with genotype non-A (96% vs 76%; P = .06) as well as HBsAg loss (58% vs 11%; P < .001). CONCLUSIONS: HBeAg loss after treatment with PEG-IFN alpha-2b alone or in combination with lamivudine is sustained in the majority of patients and is associated with a high likelihood of HBsAg loss, particularly in genotype A-infected patients. Therefore, PEG-IFN alpha-2b remains an important treatment option in this era of nucleos(t)ide analogue therapy.

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.

Reijnders JG, Pas SD, Schutten M, de Man RA, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, 's Gravendijkwal 230, Room Ha 204, 3015 CE Rotterdam, The Netherlands. · J Hepatol. · Pubmed #19231002 No free full text.

Abstract: BACKGROUND/AIMS: We investigated the efficacy of entecavir in lamivudine-experienced and -naïve patients with persistently high HBV DNA during adefovir treatment. METHODS: Fourteen chronic hepatitis B patients (57% lamivudine-experienced) with a viral load above 5log(10)copies/mL after 12months of adefovir therapy and thereafter were treated with entecavir 1mg daily. RESULTS: During a median follow-up of 15months (range: 8-23months) one of six lamivudine-naïve and none of the eight lamivudine-experienced patients achieved undetectable HBV DNA (<373copies/mL). HBeAg loss occurred in none of the subjects. Two lamivudine-experienced patients demonstrated the rtM204I mutation; no other entecavir-resistant substitutions were detected (rtI169, rtT184, rtS202, and rtM250). Two of three patients with genotypic adefovir resistance at baseline demonstrated a rapid virologic response to entecavir, but undetectable HBV DNA was not achieved. To attain a better antiviral response the dosage of entecavir was increased to 2mg daily in two patients, resulting in further viral load decline for both of them. CONCLUSIONS: Entecavir monotherapy dosed at 1mg resulted in a slow reduction of viral load in both lamivudine-experienced and -naïve patients with persistently high HBV DNA during adefovir therapy. Increasing the dosage of entecavir led to further HBV DNA decline.

Reijnders JG, Leemans WF, Hansen BE, Pas SD, de Man RA, Schutten M, Janssen HL. · Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands. · J Viral Hepat. · Pubmed #19175883 No free full text.

Abstract: Patients with chronic hepatitis B (CHB) who will and those who will not respond to adefovir (ADV) monotherapy need to be identified at an early stage in order to adjust treatment and prevent future development of antiviral resistance. In a single-centre cohort study, we investigated 76 CHB patients [50% hepatitis B e antigen (HBeAg)-positive] treated with long-term ADV monotherapy. During a median follow-up of 122 (24-185) weeks, 42 (55%) patients achieved virologic response (VR), defined as HBV-DNA levels <10(3) copies/mL, and 10 patients (13%) developed genotypic ADV resistance. Independent baseline predictors of VR were HBeAg negativity [hazard ratio (HR) 2.98; 95% confidence interval (CI) 1.24-7.19; P = 0.02], high alanine aminotransferase (ALT) levels (HR 1.11; 95% CI 1.05-1.18; P = 0.001), and low HBV-DNA levels (HR 0.56; 95% CI 0.41-0.75; P < 0.001). HBV-DNA at week 24 demonstrated a higher predictive value for VR than HBV-DNA at week 48. Important predictors of genotypic resistance were presence of cirrhosis (HR 6.54; 95% CI 1.39-30.9; P = 0.018), and not achieving VR during treatment (HR 6.60; 95% CI 1.35-32.4; P = 0.008). Patients without VR at week 24 already demonstrated a trend towards the emergence of ADV resistance (P = 0.07). HBV-DNA at week 24 was a better on-treatment predictor of VR than HBV-DNA at week 48, and ADV-resistant mutations developed more frequently in patients without VR at week 24. Therefore, our study suggests that virologic response to ADV therapy can be assessed at 24 weeks, instead of the generally recommended 48 weeks.

Baars J, Boon B, De Wit JB, Schutten M, Van Steenbergen JE, Garretsen HF, Van De Mheen D. · Addiction Research Institute, Rotterdam, The Netherlands. · Subst Use Misuse. · Pubmed #19085440 No free full text.

Abstract: The present study was conducted as an evaluation of a two-year pilot program started in 1998 in the Netherlands to provide free hepatitis B vaccination targeted at drug users (DUs). In order to identify which demographic and social-cognitive factors predict vaccination uptake, written questionnaires were distributed in three pilot regions (Amsterdam, Tiel, and Maastricht) amongst all DUs that were invited to participate in the program during a 2-month period. Vaccination behavior 2 years later was anonymously and prospectively linked to the questionnaire data, which allowed us to investigate which factors predict vaccination behavior. Of the 207 DUs eligible for vaccination (i.e., who were not immune and/or had no current infection with the virus), 93 DUs had obtained vaccination in the 2 years following the questionnaire. More than half of them (N = 50) had completed the full program (3 injections). As possible predictors of vaccination uptake, the questionnaire included constructs of the Theory of Planned Behavior as well as of the Health Belief Model. Our results show that attitude toward obtaining hepatitis B vaccination was positively associated with intention toward obtaining hepatitis B vaccination. However, perceived behavioral control was found to be the only construct related to actual vaccination uptake. None of the demographic variables were related to vaccination uptake. Our findings suggest that future interventions aimed at increasing uptake of vaccination against hepatitis B in DUs should address DUs (perceived) control concerning this behavior. The study's limitations are noted.

Götz HM, Schutten M, Borsboom GJ, Hendriks B, van Doornum G, de Zwart O. · Division of Infectious Disease Control, Municipal Public Health Service Rotterdam Rijnmond, The Netherlands. · Euro Surveill. · Pubmed #18761934 links to  free full text

Abstract: In July 2007, two residents of a nursing home were diagnosed with acute Hepatitis B virus infection. To identify risk factors for HBV infection a retrospective cohort study among residents was performed. Case finding included discharged diabetes patients and those receiving home care. Among 32 residents one case of chronic hepatitis B was found that could be identified by genotyping as the source patient for the acute cases. Diabetes and finger sticks were risk factors for HBV infection. Most likely the cause of transmission was a multiclix finger stick device developed for use in individual patients but used in multiple patients. Education and training in the use of new equipment and hygiene audits remain the cornerstones in infection control practices.

Schutten M, Fries E, Burghoorn-Maas C, Niesters HG. · Erasmus MC, Department of Virology, s-Gravendijkwal 230, 3015 CE, Rotterdam, The Netherlands. · J Clin Virol. · Pubmed #17768084 No free full text.

Abstract: BACKGROUND: Despite FDA approval and CE marking of commercial tests, manufacturer independent testing of technical aspects is important. OBJECTIVES: To evaluate the analytical performance of the new Abbott RealTime HCV and HIV-1 viral load tests. STUDY DESIGN: Sensitivity, specificity and inter-/intra-assay variation were investigated. The HCV and HIV-1 assays were compared with Siemens bDNA 3.0 and Roche Cobas Monitor 2.0, respectively, on diagnostic samples. RESULTS: Lower isolation volumes on the M1000 gave minor but statistically significant lower quantitative values. Minor differences were observed in the lower limit of detection relative to the specification given by the manufacturer. Inter-/intra-assay coefficients of variations ranged from 0.31 to 4.75 between 5.0 x 10(4) and 5.0 x 10(2) copies/mL. Both the HCV and HIV-1 Abbott RealTime tests did not show a geno-/sub-type dependent under-quantification on WHO reference panels, quality control panels or clinical specimens. The Abbott RealTime HIV-1 viral load assay detected subtype O whereas several other systems failed to detect this subtype. CONCLUSION: The technical aspects of the HCV and HIV-1 RealTime viral load assays on the M2000 system make it attractive for use in routine diagnostic settings.

Schutten M, Peters D, Back NK, Beld M, Beuselinck K, Foulongne V, Geretti AM, Pandiani L, Tiemann C, Niesters HG. · Department of Virology, Erasmus MC, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. · J Clin Microbiol. · Pubmed #17409216 links to  free full text

Abstract: The analytical performances of the new Abbott RealTime hepatitis C virus (HCV) and human immunodeficiency virus type 1 viral load assays were compared at nine laboratories with different competitor assays. These included the Abbott LcX, Bayer Versant bDNA, Roche COBAS Amplicor, and Roche COBAS TaqMan assays. Two different protocols used during the testing period with and without a pre-m1000 RNA isolation spin were compared. The difference proved to be nonsignificant. A uracil-N-glycosylase (UNG) contamination control option in the HCV test for previous Roche COBAS Amplicor users was evaluated. It proved to decrease amplicon carryover by 100-fold independent of the amplicon input concentration. The protocol including UNG proved to overcome problems with false-positive negative controls. Comparison with other assays revealed only minor differences. The largest difference was observed between the Abbott HCV RealTime assay and the Roche COBAS Amplicor HCV Monitor version 2.0 assay.

de Wit JB, Vet R, Schutten M, van Steenbergen J. · Department of Social and Organisational Psychology, Utrecht University, PO Box 80.140, 3508 TC Utrecht, The Netherlands. · Prev Med. · Pubmed #15850881 No free full text.

Abstract: BACKGROUND: Many individuals who are at risk for infection with the hepatitis B virus (HBV), including men who have sex with men (MSM), are not vaccinated. This study assessed social-cognitive determinants of obtaining vaccination against HBV. METHODS: A targeted survey was conducted among 432 MSM by means of a written questionnaire that contained assessments of social-cognitive determinants of vaccination behavior derived from the Health Belief Model (HBM) and the Theory of Planned Behavior. Vaccination behavior was anonymously linked to questionnaire data for which informed consent was obtained. RESULTS: Of the 290 men eligible for vaccination, 248 (86%) had obtained vaccination. Multivariate logistic regression analysis showed that these men were younger, more often were in a steady relationship, and had fewer sex partners. In addition, significant effects were also found for central factors proposed by the Health Belief Model. Notably, men who obtained vaccination against HBV perceived more personal threat from HBV. None of the Theory of Planned Behavior variables were related to obtaining vaccination. CONCLUSIONS: Findings suggest that health education interventions that address perceived susceptibility and severity are likely to contribute to increased uptake of HBV vaccination among MSM. Influencing perceived susceptibility in particular is important, more so than increasing perceived severity by scare tactics.

Schutten M, de Wit JB, van Steenbergen JE. · Municipal Health Service Amsterdam, HIV & STI Research, PO Box 2200, 1000 CE Amsterdam, The Netherlands. · Int J STD AIDS. · Pubmed #11839162 No free full text.

Abstract: We assessed to what extent gay men are motivated to obtain vaccination against hepatitis B virus (HBV), as well as the social cognitive determinants of this motivation. A cross-sectional survey was conducted among homosexual men by means of a written questionnaire that contained assessments of intention, knowledge and social-cognitive determinants of intention (i.e. attitude, social norm and perceived behavioural control towards vaccination, perceived severity and perceived vulnerability regarding HBV infection). Four hundred and thirty-three homosexual men completed the questionnaire. We conducted a linear regression analysis to determine the contribution of social-cognitive variables in explaining intention to be vaccinated. Attitude, social norm and perceived vulnerability were significant predictors of intention. Usually, health education emphasizes the severity of a disease, but from this analysis we can conclude that gay men should be convinced of their personal vulnerability to HBV, the benefits of vaccination, and that important referents of the targeted person think positively about vaccination.

Heijtink RA, Kruining J, van Bergen P, de Rave S, van Hattum J, Schutten M, Osterhaus AD. · Department of Virology, Erasmus University Rotterdam, Rotterdam, The Netherlands. · J Med Virol. · Pubmed #11793381 No free full text.

Abstract: A human monoclonal antibody type IgG4, designated 1Ff4, was obtained by Epstein Barr virus transformation of peripheral blood lymphocytes from a hepatitis B vaccinee (HB-VAX: plasma-derived vaccine) after one boost of yeast recombinant DNA derived vaccine (Engerix-B). 1Ff4 binds preferentially to HBsAg/adw(2) and HBsAg/ayw(1). In binding experiments, it competes with antibodies induced by vaccination with HB-VAX-DNA (yeast recombinant) and HB-VAX (plasma-derived vaccine). 1Ff4 competes in part with a monoclonal antibody for the w/r region. Partial inhibition of binding of HBsAg/adw(2) to solid phase anti-HBs was detected, resembling inhibition obtained using other human monoclonal specific for the "a"-loop. 1Ff4 does not bind to linear peptides covering the two "a"-loops or to an adw(2)/G145R mutant, its binding to wild type HBsAg strongly depends on the presence of disulphide bonds. In a large series of HBsAg-positive samples from an endemic area, 1Ff4 antibodies were successfully used to discriminate between an adw(2) and an adrq+ strain. The characterisation of 1Ff4 and other human monoclonal anti-HBs antibodies may help to understand the fine specificity of protective antibodies elicited by immunization.