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Cardell, Kristina
Publications (10 of 12) Show all publications
Hedenstierna, M., Weiland, O., Brass, A., Bankwitz, D., Behrendt, P., Uhnoo, I., . . . Brenndörfer, E. D. (2015). Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.. Alimentary Pharmacology and Therapeutics, 41(6), 532-543
Open this publication in new window or tab >>Long-term follow-up of successful hepatitis C virus therapy: waning immune responses and disappearance of liver disease are consistent with cure.
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2015 (English)In: Alimentary Pharmacology and Therapeutics, ISSN 0269-2813, E-ISSN 1365-2036, Vol. 41, no 6, p. 532-543Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: A sustained viral response (SVR) after interferon-based therapy of chronic hepatitis C virus (HCV) infection is regarded to represent a cure. Previous studies have used different markers to clarify whether an SVR truly represents a cure, but no study has combined a clinical work-up with highly sensitive HCV RNA detection, and the determination of immune responses.

AIM: To determine clinical, histological, virological and immunological markers 5-20 years after SVR.

METHODS: In 54 patients, liver biochemistry, histology and elastography were evaluated. Liver biopsies, plasma and peripheral blood mononuclear cells (PBMCs) were tested for minute amounts of HCV RNA. HCV-specific T-cell responses were monitored by ELISpot and pentamer staining, and humoral responses by measuring HCV nonstructural (NS)3-specific antibodies and virus neutralisation.

RESULTS: Liver disease regressed significantly in all patients, and 51 were HCV RNA-negative in all tissues tested. There was an inverse association between liver disease, HCV-specific T-cell responses and HCV antibody levels with time from SVR, supporting that the virus had been cleared. The three patients, who all lacked signs of liver disease, had HCV RNA in PBMCs 5-9 years after SVR. All three had HCV-specific T cells and NS3 antibodies, but no cross-neutralising antibodies.

CONCLUSIONS: Our combined data confirm that a SVR corresponds to a long-term clinical cure. The waning immune responses support the disappearance of the antigenic stimulus. Transient HCV RNA traces may be detected in some patients up to 9 years after SVR, but no marker associates this with an increased risk for liver disease.

National Category
Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-113807 (URN)10.1111/apt.13096 (DOI)000349617000003 ()25627143 (PubMedID)
Note

EDB was supported by grants from the Swedish Society for Medical Research, the Ruth and Richard Julin Foundation, the Professor Nanna Svartz Fund, the Ake Wiberg Foundation, the Clas Groschinsky Memorial Foundation, the Goljes Memorial Fund, the Lars Hierta Memorial Foundation, the Erik and Edith Fernstrom Foundation and from Karolinska Institutet. MS was supported by the Swedish Cancer Society, the Swedish Research Council, the Stockholm County Council and Vinnova. OW was funded by Schering-Plough and MSD. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

Available from: 2015-01-30 Created: 2015-01-30 Last updated: 2017-12-05
Sjöwall, C., Martinsson, K., Cardell, K., Ekstedt, M. & Kechagias, S. (2015). Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in nonalcoholic fatty liver disease. Translational research : the journal of laboratory and clinical medicine, 165(6), 658-666
Open this publication in new window or tab >>Soluble urokinase plasminogen activator receptor levels are associated with severity of fibrosis in nonalcoholic fatty liver disease
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2015 (English)In: Translational research : the journal of laboratory and clinical medicine, ISSN 1878-1810, Vol. 165, no 6, p. 658-666Article in journal (Refereed) Published
Abstract [en]

The identification of individuals with severe liver fibrosis among patients with chronic liver disease is of major importance when evaluating prognosis, potential risk for complications, and when deciding treatment strategies. Although percutaneous liver biopsy is still considered a "gold standard" for staging of liver fibrosis, attempts to find reliable noninvasive markers of liver fibrosis are frequent. Inflammation is essential for the progression of fibrosis. The urokinase plasminogen activator and its receptor have been associated with hepatic inflammation and fibrosis in mice. High serum concentrations of soluble urokinase plasminogen activator receptor (suPAR) are suggested to be involved in inflammation, tissue remodeling, and cancer metastasis. Here, we evaluated serum suPAR as a noninvasive test to detect liver fibrosis in 82 well-characterized patients with nonalcoholic fatty liver disease (NAFLD), and in 38 untreated patients with chronic hepatitis C virus (HCV) infection at the time of their first liver biopsy. suPAR levels were increased in chronic liver disease compared with blood donors (P < 0.001). Patients with HCV had higher suPAR concentrations than patients with NAFLD (P < 0.002). suPAR levels were associated with the severity of fibrosis, particularly in NAFLD, but did not correlate with inflammation. Regarding the performance in predicting severity of fibrosis, suPAR was essentially as good as other commonly used noninvasive fibrosis scoring systems. The results in HCV confirm previous observations. However, this is the first study to investigate suPAR as a biomarker in NAFLD, and the results indicate that suPAR may constitute a severity marker related to fibrosis and prognosis rather than reflecting inflammation.

Place, publisher, year, edition, pages
Elsevier, 2015
National Category
Clinical Medicine Basic Medicine
Identifiers
urn:nbn:se:liu:diva-112698 (URN)10.1016/j.trsl.2014.09.007 (DOI)000354912600003 ()25445207 (PubMedID)
Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2018-01-11
Rondahl, E., Gruber, M., Joelsson, S., Sundqvist, M., Åkerlind, B., Cardell, K., . . . Serrander, L. (2014). The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer.. Journal of Clinical Virology, 60(2), 172-173
Open this publication in new window or tab >>The risk of HCV RNA contamination in serology screening instruments with a fixed needle for sample transfer.
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2014 (English)In: Journal of Clinical Virology, ISSN 1386-6532, E-ISSN 1873-5967, Vol. 60, no 2, p. 172-173Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Hepatitis C diagnostics involve antibody screening and confirmation of current infection by detection of HCV RNA positivity. In screening instruments with fixed pipetting needle, there is a risk of sample carry-over contamination.

OBJECTIVES: The aim of this study was to evaluate the risk of such contamination in a proposed clinical setting.

STUDY DESIGN: In the present study, known HCV RNA positive (n=149) and negative (n=149) samples were analysed by anti-HCV Abbott in an Architect instrument in an alternating fashion in order to test for contamination.

RESULTS: In subsequent retesting of the previously HCV RNA-negative samples, six samples (4%) were positive by the Cobas Taqman assay with a maximum level of 33IU/mL. The results show that there is a risk for transfer of HCV in the Architect instrument but they also show that the levels of HCV RNA observed are low.

CONCLUSIONS: We conclude that complementary HCV RNA testing on samples identified as anti-HCV positive by screening can be recommended because the complementary results are reliable in the majority of cases when either HCV RNA is negative or HCV RNA is positive with a level >1000IU/mL. In a minority of cases, with low HCV RNA after anti-HCV antibody screening, cross-contamination should be suspected and a new sample requested for HCV RNA testing. This strategy would reduce the need for obtaining a new sample from the vast majority of patients with a newly discovered HCV antibody positivity.

National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-107297 (URN)10.1016/j.jcv.2014.03.011 (DOI)000335738000016 ()24735614 (PubMedID)
Available from: 2014-06-10 Created: 2014-06-10 Last updated: 2018-01-11
Ydreborg, M., Westin, J., Rembeck, K., Lindh, M., Norgren, H., Holmberg, A., . . . Lagging, M. (2013). Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Transient Elastography in Chronic Hepatitis C Infection. PLoS ONE, 8(11), e80172
Open this publication in new window or tab >>Impact of IL28B-Related Single Nucleotide Polymorphisms on Liver Transient Elastography in Chronic Hepatitis C Infection
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2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, p. e80172-Article in journal (Refereed) Published
Abstract [en]

Background and Aims

Recently, several genome-wide association studies have revealed that single nucleotide polymorphisms (SNPs) in proximity to IL28B predict spontaneous clearance of hepatitis C virus (HCV) infection as well as outcome following pegylated interferon and ribavirin therapy among genotype 1 infected patients. Additionally the presence of the otherwise favorable IL28B genetic variants in the context of HCV genotype 3 infection reportedly entail more pronounced liver fibrosis and steatosis. The present study aimed to evaluate the impact of IL28B SNP variability on liver stiffness as accessed by transient elastography.

Methods

Seven hundred and seventy-one Swedish HCV infected patients sequentially undergoing liver stiffness measurement by means of Fibroscan® in the context of a real-life trial had samples available for IL28B genotyping (rs12979860) and HCV genotyping.

Results

CCrs12979860 was more common among HCV genotype 2 or 3 infected treatment-naïve patients than among those infected with genotype 1 (P<0.0001). Additionally CCrs12979860 among HCV genotype 3 infected patients was associated with higher liver stiffness values (P = 0.004), and higher AST to platelet ratio index (APRI; p = 0.02) as compared to carriers of the T allele. Among HCV genotype 1 infected patients, CCrs12979860 was significantly associated with higher viral load (P = 0.001), with a similar non-significant trend noted among HCV genotype 3 infected patients.

Conclusion

This study confirms previous reports that the CCrs12979860 SNP is associated with more pronounced liver pathology in patients chronically infected with HCV genotype 3 as compared to genotype 1, suggesting that IL28B genetic variants differently regulates the course of HCV infection across HCV genotypes.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102375 (URN)10.1371/journal.pone.0080172 (DOI)000327143800131 ()
Available from: 2013-12-09 Created: 2013-12-09 Last updated: 2017-12-06
Sjöwall, C., Cardell, K., Bokarewa, M. I., Enocsson, H., Ekstedt, M., Lindvall, L., . . . Almer, S. (2012). High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation. Human Immunology, 73(4), 382-388
Open this publication in new window or tab >>High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation
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2012 (English)In: Human Immunology, ISSN 0198-8859, E-ISSN 1879-1166, Vol. 73, no 4, p. 382-388Article in journal (Refereed) Published
Abstract [en]

The presence of autoantibodies against C-reactive protein (anti-CRP) has been reported in association with autoimmunity and histopathology in chronic hepatitis C virus (HCV) infection. Resistin could play a role in the pathogenesis of hepatitis, although results on HCV infection are ambiguous. Here we retrospectively analyzed anti-CRP and resistin levels in the sera of 38 untreated and well-characterized HCV patients at the time of their first liver biopsy. HCV activity and general health were assessed by a physician at least yearly until follow-up ended. Anti-CRP and resistin were also measured in patients with autoimmune hepatitis (AIH) and nonalcoholic fatty liver disease (NAFLD). Anti-CRP antibodies were registered in all HCV patients, whereas only a few AIH (11%) and NAFLD (12%) sera were positive. Anti-CRP levels were related to histopathological severity and were highest in patients with cirrhosis at baseline. Resistin levels were similar in HCV, AIH, and NAFLD patients, but high levels of resistin were associated with early mortality in HCV patients. Neither anti-CRP nor resistin predicted a response to interferon-based therapy or cirrhosis development or was associated with liver-related mortality. We conclude that anti-CRP antibodies are frequently observed in chronic HCV infection and could be a useful marker of advanced fibrosis and portal inflammation.

Place, publisher, year, edition, pages
Elsevier, 2012
Keywords
Hepatitis C, Autoantibodies, C-reactive protein, Resistin, Interferon-alpha
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-77333 (URN)10.1016/j.humimm.2012.01.009 (DOI)000302986200010 ()
Note
Funding Agencies|Swedish Society for Medical Research||Professor Nanna Svartz Foundation||King Gustaf V 80-Year Foundation||Sweden-America Foundation||County Council of Ostergotland||Clas Groschinsky||byggmastare Olle Engkvist||apotekare Hedberg||Available from: 2012-05-11 Created: 2012-05-11 Last updated: 2017-12-07
Cardell, K. (2009). Studies on Hepatitis B Vaccination and Factors Associated withthe Vaccine Response. (Doctoral dissertation). Linköping: Linköping University Electronic Press
Open this publication in new window or tab >>Studies on Hepatitis B Vaccination and Factors Associated withthe Vaccine Response
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Hepatitis B virus causes liver disease and up to 2 billion people have been in contact with the virus world wide. It can cause both acute and chronic disease. The routes for transmission are through blood, mother to infant at time of delivery and sexually. Chronic hepatitis B infection is a risk factor for development of liver cirrhosis and hepatocellular carcinoma. Prevention of hepatitis B virus infection is highly desirable. Since the early1980s hepatitis B vaccine has been available. It can effectively prevent the disease and has been found to be safe. The World Health Organisation, WHO, has recommended all countries to implement the vaccine in their children’s vaccination programmes and many countries have followed this recommendation. In Sweden so far the recommendation is vaccination of identified risk groups for hepatitis B. Health care workers who are at risk of having blood contact in their work is one such risk group.

In a large study on health care workers who were intradermally vaccinated with the hepatitis B vaccine, 960/1406 (68.3%) developed protective levels of antibodies to HBsAg (anti-HBs; defined as >10 mIU/mL) after three doses. After administering of an additional fourth dose to non-responders the response rate was 1187/1335 (88.9%). Risk factors for non-response were smoking and age above 40 years. Also, the vaccine response rates improved during the study and a risk of giving a too small dose with intradermal administration was also identified. This suggests that intradermal administration is dependent on well trained personnel.

A genetic factor which has been proposed to be associated with a non-responder status to HBV vaccination is the HLA haplotype of the host. In a study in on 69 responders and 53 non-responders the haplotypes were therefore determined. It was found that [DQB1*0602; DQA1*0102; DR15] and [DQB1*0603; DQA1*0103; DRB1*1301] were more likely to be found in responders (p<0.025 and p<0.05 respectively). In non-responders the haplotype [DQB1*0604; DQA1*0102; DRB1*1302] was found more frequently (p<0.005). This study supports that the HLA class II of the host is involved in the ability to respond to the HBV vaccination.

To further test the genetic link between the HLA of the host and a non-responder status, relatives to known intradermal non-responders with known haplotypes for DQA1, DQB1 and DRB1 were vaccinated in the same way, intradermally. The response rate in the relatives was 15/26 (58%) which is lower than expected suggesting a genetic influence on the vaccine response. In this study 5/6 with the haplotype [DQB1*0604; DQA1*0102; DRB1*1302] were non-responders which is in line with the previous data that this haplotype is correlated to hepatitis B vaccine non-response.

Finally, to test a strategy by which we could induce an effective anti-HBs seroconversion in non-responders we revaccinated these with the combined hepatitis A and B vaccine intramuscularly at a double dose. Already after the first revaccination dose 26/44 (60%) responded with protective antibodies compared to 2/20 (10%) in a vaccine naïve reference group, suggesting an anamnestic response. After three doses 42/44 (95%) responded in the non-responder group and 20/20 (100%) in the reference group. All participants in the study responded to the hepatitis A antigen.

In conclusion these studies show that intradermal vaccine administration can be used and is effective, and that the ability to respond is influenced by several, including genetic, factors. Importantly a non-responder status to hepatitis B vaccination is not absolute, a double dose of the combined HAV and HBV vaccine effectively overcomes this non-response in most individuals.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2009. p. 67
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1127
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20800 (URN)978-91-7393-634-7 (ISBN)
Public defence
2009-10-20, Elsa Brändströmsalen, Hälsouniversitetet, Campus US, Linköpings Universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2012-05-09Bibliographically approved
Cardell, K., Åkerlind, B., Sällberg, M. & Frydén, A. (2008). Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine. Journal of Infectious Diseases, 198(3), 299-304
Open this publication in new window or tab >>Excellent response rate to a double dose of the combined hepatitis A and B vaccine in previous nonresponders to hepatitis B vaccine
2008 (English)In: Journal of Infectious Diseases, ISSN 0022-1899, E-ISSN 1537-6613, Vol. 198, no 3, p. 299-304Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Hepatitis B vaccine has been shown to be highly efficient in preventing hepatitis B. However, 5%-10% of individuals fail to develop protective levels (>or=10 mIU/mL) of antibodies to hepatitis B surface antigen (anti-HBs) and are considered to be nonresponders.

METHODS: A total of 48 nonresponders and 20 subjects naive to the HBV vaccine received a double dose of combined hepatitis A and B vaccine (Twinrix) at 0, 1, and 6 months. The levels of anti-HBs and antibodies to hepatitis A virus (anti-HAV) were determined before vaccination and 1 month after each dose.

RESULTS: Among 44 nonresponders, protective anti-HBs levels were found in 26 (59%) after the first dose and in 42 (95%) after the third dose. Among the control subjects, the corresponding figures were 10% and 100%, respectively. All subjects seroconverted to anti-HAV. The titers of both anti-HBs and anti-HAV were lower in the previously nonresponsive subjects (P< .01).

CONCLUSION: Revaccination of nonresponders to the standard hepatitis B vaccine regimen with a double dose of the combined hepatitis A and B vaccine was highly effective. This is most likely explained by the increased dose, a positive bystander effect conferred by the hepatitis A vaccine, or both.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20799 (URN)10.1086/589722 (DOI)18544037 (PubMedID)
Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
Nyström, J., Cardell, K., Bjorg Bjornsdottir, T., Frydén, A., Hultgren, C. & Sallberg, M. (2008). Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine. Vaccine, 26(47), 5967-5972
Open this publication in new window or tab >>Improved cell mediated immune responses after successful re-vaccination of non-responders to the hepatitis B virus surface antigen (HBsAg) vaccine using the combined hepatitis A and B vaccine
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2008 (English)In: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 26, no 47, p. 5967-5972Article in journal (Refereed) Published
Abstract [en]

We Successfully re-vaccinated hepatitis B Virus (HBV) vaccine non-responders Using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine. The hope was to improve priming of hepatitis B surface antigen (HBsAg)-specific cell mediated immune response (CMI) by an increased antigen dose and a theoretical adjuvant-effect from the local presence of a HAV-specific CMI. A few non-responders had a detectable HBsAg-specific CMI before re-vaccination. An in vitro detectable HBsAg-specific CMI was primed equally effective in non-responders (58%) as in first time vaccine recipients (68%). After the third dose a weak, albeit significant, association was observed between the magnitude of HBsAg-specific proliferation and anti-HBs levels. This regimen improves the priming of HBsAg-specific CMIs and antibodies.

Keywords
Hepatitis B virus, HBV, HBsAg, Vaccine, Non-responder
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-16233 (URN)10.1016/j.vaccine.2008.08.054 (DOI)
Available from: 2009-01-12 Created: 2009-01-09 Last updated: 2017-12-14
Cardell, K., Widell, A., Frydén, A., Åkerlind, B., Månsson, A.-S., FranzÉn, S., . . . Isaksson, B. (2008). Nosocomial hepatitis C in a thoracic surgery unit, retrospective findings generating a prospective study. Journal of Hospital Infection, 68(4), 322-328
Open this publication in new window or tab >>Nosocomial hepatitis C in a thoracic surgery unit, retrospective findings generating a prospective study
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2008 (English)In: Journal of Hospital Infection, ISSN 0195-6701, E-ISSN 1532-2939, Vol. 68, no 4, p. 322-328Article in journal (Refereed) Published
Abstract [en]

We describe the transmission of hepatitis C virus (HCV) to two patients from a thoracic surgeon who was unaware of his hepatitis C infection. By partial sequencing of the non-structural 5B gene and phylogenetic analysis, the viruses from both patients were found to be closely related to genotype 1a strain from the surgeon. Two further hepatitis C cases were found in relation to the thoracic clinic. Their HCV sequences were related to each other but were of genotype 2b and the source of infection was never revealed. To elucidate the magnitude of the problem, we conducted a prospective study for a period of 17 months in which patients who were about to undergo thoracic surgery were asked to participate. Blood samples were drawn prior to surgery and at least four months later. The postoperative samples were then screened for anti-HCV and, if positive, the initial sample was also analysed. The only two patients (0.4%) identified were confirmed anti-HCV positive before surgery, and none out of 456 evaluable cases seroconverted to anti-HCV during the observation period. Despite the retrospectively identified cases, nosocomial hepatitis C is rare in our thoracic unit. The study points out the risk of transmission of hepatitis C from infected personnel and reiterates the need for universal precautions. © 2008 The Hospital Infection Society.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-43217 (URN)10.1016/j.jhin.2007.12.008 (DOI)72981 (Local ID)72981 (Archive number)72981 (OAI)
Available from: 2009-10-10 Created: 2009-10-10 Last updated: 2017-12-13
Cardell, K., Frydén, A. & Normann, B. (1999). Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise. Scandinavian Journal of Infectious Diseases, 31(2), 197-200
Open this publication in new window or tab >>Intradermal hepatitis B vaccination in health care workers. Response rate and experiences from vaccination in clinical practise
1999 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 31, no 2, p. 197-200Article in journal (Refereed) Published
Abstract [en]

Health care workers at risk for hepatitis B virus infection are recommended for vaccination. Low-dose intradermal (i.d.) administration of vaccine has been suggested as a less expensive alternative to intramuscular (i.m.) inoculation. To evaluate the i.d. vaccination route, health care workers were included in a prospective study. The subjects were vaccinated with 0.1 ml (= 2 microg) recombinant vaccine (Engerix B, SmithKline Beecham) i.d. at 0, 1 and 6 months. Two months after the third vaccination, measurement of the anti-HBs level was conducted. An anti-HBs level > or =10 IU/l was considered protective. Those with an anti-HBs level <10 IU/l were given a fourth dose with new serological control after another 2 months. The results are based on the 1406 subjects that it was possible to evaluate. The seroconversion rate to protective anti-HBs level after 3 doses was 68% and after 3 or 4 doses 89%. Factors associated with a lower response rate were increasing age (p<0.05) and smoking (p<0.001). Sex or body mass index had no influence on the results. Vaccination technique seems to be of utmost importance when the i.d. route is used. Well instructed and experienced nurses are required and quality control with follow-up of overall seroconversion rate within each centre is needed.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-20796 (URN)10.1080/003655499750006272 (DOI)10447332 (PubMedID)
Available from: 2009-09-21 Created: 2009-09-21 Last updated: 2017-12-13Bibliographically approved
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