| 1. |
- Lindh, Magnus, 1960, et al.
(författare)
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Treatment of chronic hepatitis B infection : an update of Swedish recommendations
- 2008
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Ingår i: Scandinavian Journal of Infectious Diseases. - London : Taylor & Francis. - 0036-5548 .- 1651-1980. ; 40:6-7, s. 436-450
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Forskningsöversikt (refereegranskat)abstract
- The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.
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| 2. |
- Alestig, Erik, 1973, et al.
(författare)
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Genetic diversity of genotype D3 in acute hepatitis B
- 2013
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Ingår i: Journal of Medical Virology. - : Wiley. - 0146-6615. ; 85:7, s. 1148-1154
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Tidskriftsartikel (refereegranskat)abstract
- Acute hepatitis B related to injection drug use is often caused by HBV-D3, a subgenotype that probably was introduced in Western Europe in the 1960s. The aim of this study was to describe genetic change over time in injection drug use-related HBV-D3 in one geographic area. Fourteen complete genomes and partial genomic regions of 17 HBV strains of subgenotype D3 causing acute (n=30) or chronic (n=1) hepatitis B at different time points between 1975 and 2009 were investigated. The 14 complete genomes clustered in phylogenetic trees on a sub-branch of HBV-D3 along with a few published sequences with high bootstrap values. In contrast, the phylogenetic tree topology based on nucleotides coding for surface antigen or core was uncertain with bootstrap values below 70% or lower. Variation of nucleotides coding for amino acids 125, 136, and 143 in the a determinant of HBsAg was however linked to complete genome phylogeny, indicating that these codons might be useful as markers for clades. The results show that knowledge about circulating strains is critical for the interpretation of molecular epidemiology investigations. The low degree of genetic change over time of HBV-D3 in the studied groups suggests that outbreaks of acute hepatitis B in injection drug users might originate from a limited number of individuals with chronic infection. Classification based on core or S region phylogeny obtained poor support from bootstrap values, but the presence of clade-specific amino acid substitutions suggests that the S region may be useful for subgenomic molecular epidemiology of HBV.
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| 3. |
- Asteberg, Inger, et al.
(författare)
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A food-borne streptococcal sore throat outbreak in a small community.
- 2006
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Ingår i: Scandinavian journal of infectious diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 38:11-12, s. 988-94
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Tidskriftsartikel (refereegranskat)abstract
- Beta-haemolytic group A streptococci (GAS) is a common cause of sore throat, usually spread person-to-person. Outbreaks related to infected food have more seldom been reported. The bacteria may originate from the throat or from wounds on the hands of persons handling the food. An outbreak in Sätila, Sweden, in April/May 2003 involving 153 individuals who fell ill after eating contaminated 'sandwich-layer cakes' was investigated in a descriptive, retrospective cohort study. Questionnaires were distributed, one immediately after the outbreak and one 3 months later. The average attack rate was 72%. 143 individuals sought medical care and 137 were treated with antibiotics. 76 individuals were ill for more than 4 days. GAS isolates of identical T-type were obtained from the throats of the patients, wounds on the caterer's fingers and also from the cakes. PFGE banding patterns of 14 representative isolates were identical, as well as the emm-sequence type, emm 89, of 3 chosen isolates. The study shows that GAS from a small wound on a finger can cause illness in a large number of individuals. To prevent further outbreaks, it is important to increase public awareness of this type of transmission.
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| 4. |
- Berg, Cecilia, 1976-, et al.
(författare)
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Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase
- 2006
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 96:5, s. 652-659
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Tidskriftsartikel (refereegranskat)abstract
- Proliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A2 inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1-2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis. © 2006 Schattauer GmbH, Stuttgart.
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| 5. |
- Hannoun, Charles, 1967, et al.
(författare)
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Phylogeny of African complete genomes reveals a West African genotype A subtype of hepatitis B virus and relatedness between Somali and Asian A1 sequences.
- 2005
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Ingår i: The Journal of general virology. - : Microbiology Society. - 0022-1317 .- 1465-2099. ; 86:Pt 8, s. 2163-7
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Tidskriftsartikel (refereegranskat)abstract
- Hepatitis B virus (HBV) is a major cause worldwide of liver disease, including hepatocellular carcinoma. There are eight known genotypes (A-H), of which genotype A has been divided into two subtypes: A2, prevalent in Europe, and A1, which is prevalent in sub-Saharan Africa, but also occurs in southern Asia. In this study, which includes 14 new complete genomes of non-European genotype A HBV, it was found that West African strains seem to constitute a new subgroup, A3. The high degree of genetic diversity within Africa indicates that genotype A originates from Africa. Based on a 2 % genetic distance between Asian and Somali sequences, it seems that the A1 subtype has spread from East Africa to southern Asia during the last 1000-2000 years. Moreover, it is proposed here that the A2 subtype originates from southern Africa and was imported to Europe around 500 years ago or later. The finding of T-1809/1812 close to the precore start codon and T-1862 and A-1888 in the precore region in HBV e antigen-positive children with signs of a mimimal immune response indicates that these substitutions are stable variants, rather than mutations emerging during infection in individual carriers.
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| 6. |
- Krivospitskaya, Olesya, 1983-, et al.
(författare)
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A CYP26B1 polymorphism enhances retinoic acid catabolism and may aggravate atherosclerosis
- 2012
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Ingår i: Molecular Medicine. - New York, USA : The Feinstein Institute for Medical Research. - 1076-1551 .- 1528-3658. ; 18:1, s. 712-718
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Tidskriftsartikel (refereegranskat)abstract
- All-trans retinoic acid, controlled by CYP26 enzymes, potentially has beneficial effects in atherosclerosis treatment. This study investigates CYP26B1 in atherosclerosis and effects of a genetic polymorphism in CYP26B1 on retinoid catabolism. We found that CYP26B1 mRNA was induced by retinoic acid in human atherosclerotic arteries and CYP26B1 and the macrophage marker CD68 co-localized in human atherosclerotic lesions. In mice, Cyp26B1 mRNA was higher in atherosclerotic than normal arteries. Databases were queried for non-synonymous CYP26B1 SNPs and rs2241057 selected for further studies. Constructs of the CYP26B1 variants were created and used for production of purified proteins and transfection of macrophage-like cells. The minor variant catabolized retinoic acid with significantly higher efficiency, indicating that rs2241057 is functional and suggesting reduced retinoid availability in tissues with the minor variant. rs2241057 was investigated in a Stockholm Coronary Atherosclerosis Risk Factor (SCARF) subgroup. The minor allele was associated with slightly larger lesions as determined by angiography. In summary, this study identifies the first CYP26B1 polymorphism that alters CYP26B1 capacity to metabolize retinoic acid. CYP26B1 was expressed in macrophage-rich areas of human atherosclerotic lesions, induced by retinoic acid and increased in murine atherosclerosis. Taken together, the results indicate that CYP26B1 capacity is genetically regulated and suggest that local CYP26B1 activity may influence atherosclerosis.
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| 7. |
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| 8. |
- Skovbjerg, Susann, 1973, et al.
(författare)
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Low rate of pneumococci non-susceptible to penicillin in healthy Swedish toddlers.
- 2013
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Ingår i: Scandinavian Journal of Infectious Diseases. - : Informa UK Limited. - 0036-5548 .- 1651-1980. ; 45:4, s. 279-284
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Tidskriftsartikel (refereegranskat)abstract
- Background: Infection caused by Streptococcus pneumoniae is the leading cause of mortality in children worldwide. The aim of this study was to determine if a noted increase in non-susceptibility to penicillin among pneumococcal clinical isolates from young children reflected a similar increase in healthy children. Methods: During 2004-2005, before the conjugate pneumococcal vaccine was introduced in Sweden, 663 healthy children (13-24 months of age) attending 17 child health centres in Gothenburg, Sweden, were cultured for bacteria in the nasopharynx. Social factors were identified through a parental questionnaire. Pneumococcal serotypes and antibiotic resistance rates were determined. Antibiotic resistance was also monitored in 162 simultaneously obtained nasopharyngeal pneumococci isolated from clinical samples. Results: The healthy children frequently carried pneumococci (45%), Moraxella catarrhalis (54%), and Haemophilus influenzae (22%). The carriage rates for all these pathogens were higher in children attending day care centres compared to children staying at home (p < 0.001). The dominating pneumococcal serotypes were 6B, 19F, 23F, and 6A. Non-susceptibility to penicillin was low (4.0%) and only exceeded by that to trimethoprim-sulfamethoxazole (9.8%). Both rates were higher in the clinical isolates (9.3% and 16.7%, respectively; p < 0.05). No relationships to geographic area, day care attendance, recent antibiotic use, or travel abroad were shown for any specific serotype or for the presence of penicillin-non-susceptible pneumococci in the healthy children. Conclusions: Pneumococcal resistance rates in the healthy child population were low and did not reflect the higher rates noted at the laboratory in clinical samples obtained before and during the study.
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| 9. |
- Söderström, Ann, 1961
(författare)
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Chronic hepatitis B in children
- 2003
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Chronic hepatitis B affects more than 350 million people. In areas of high and intermediate endemicity, hepatitis B virus (HBV) infection is mainly contracted in the perinatal period or early childhood, and many of them become chronic carriers. Most children with chronic HBV infection are asymptomatic in spite of high levels of viremia, but run a long-term risk of developing liver cirrhosis or hepatocellular cancer later in life. HBV is not cytopathic, but the liver damage is considered to be caused by the immune response. Markers that identify children with a more severe prognosis are lacking. Further knowledge is also required about factors predicting and measuring response to interferon treatment. HBV vaccination is safe and effective but up to 10% of children born to HBeAg-positive mothers still become vertically infected in spite of immunoprophylaxis. It is not known if HBV DNA levels in these cases are particularly high, nor if or how pregnancy itself influences viremia levels.In an epidemiological study of children with chronic HBV living in Gothenburg, 93 children originating from 21 different countries were identified. Children from Asia were more often HBeAg positive, probably reflecting a higher proportion of vertically infected children. Fifty-four children were HBeAg positive and all but three had detectable HBV DNA by PCR. None of the children reported any symptom of hepatitis although nearly 40% had elevated aminotransferases. Only 3 out of 81 children had a previously diagnosed HBV infection when arriving in Sweden. Twelve children were born in Sweden to mothers of foreign origin; 11 of these had probably become infected vertically, in 3 cases in spite of immunoprophylaxis.Histological scoring was done in 71 children. Asian origin and presumed vertical transmission was associated with less liver damage. All HBeAg-negative children had low HBV DNA levels and mild or moderate liver inflammation. Precore mutations were found in nearly 50% of HBeAg-negative children, without association to HBV DNA level or liver damage. In HBeAg-positive carriers, a cytosine at position 1858 was associated with higher inflammation scores.Twenty-eight children were treated with interferon after priming with prednisolone. Both pretreatment and midtreatment HBV DNA levels were predictive of a sustained response. Seroconversion to anti-HBe and a viremia level < 1 million copies/mL was observed in 9 out of 28 children one year after the end of treatment.HBV DNA was analysed repeatedly in 55 pregnancies, showing values ranging from 108.1 to 109.5 copies/mL in 9 HBeAg-positive, and from undetectable (<100) to 106.8 copies/mL in 46 HBeAg-negative pregnancies. Post partum both viremia and ALT levels increased significantly. None of 243 HBeAg-negative pregnancies resulted in vertical transmission, but this had occurred, despite immune prophylaxis, in 3 out of 21 HBeAg-positive mothers, all of whom had very high HBV DNA levels (above 109.3 copies/mL).In summary, this study contributes to a better understanding of the epidemiology and pathogenesis of chronic hepatitis B in children in a low prevalence area. In addition, predictors for response to interferon therapy were identified, and the impact of pregnancy on viremia levels and inflammation, as well as the importance of viremia levels for vertical transmission of HBV, was demonstrated.
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| 10. |
- Söderström, Ann, 1961, et al.
(författare)
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Hepatitis B virus DNA during pregnancy and post partum: aspects on vertical transmission.
- 2003
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Ingår i: Scandinavian journal of infectious diseases. - 0036-5548. ; 35:11-12, s. 814-9
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about how pregnancy influences viremia levels in women with chronic hepatitis B virus infection. In this study, we first retrospectively analysed changes in HBV DNA levels during and after 55 pregnancies in HBsAg-positive women, of whom 9 were HBeAg-positive. Secondly, HBV DNA levels in 3 HBeAg-positive mothers whose babies became chronic HBV carriers, were compared with levels in 18 mothers whose babies were not infected by HBV. We found that HBV DNA ranged from 10(8.1) to 10(9.5) copies/mL in HBeAg-positive, and from undetectable (< 100) to 10(6.8) copies/mL in HBeAg-negative mothers. HBV DNA increased by a mean of 0.4 log late in pregnancy or early post partum; in 4 out of 16 HBeAg negative mothers by > 1 log during pregnancy. Post partum ALT increased in both HBeAg-positive and negative women. HBV DNA was 10(9.4)-10(10.4) copies/mL in 3 HBeAg-positive mothers whose babies were, as compared to < 100-10(10.4) copies/mL in 18 whose babies were not, vertically infected. Although the majority of HBeAg-negative women had low and relatively stable HBV DNA during pregnancy, viremia was also relatively high in some HBeAg-negative mothers, and both viremia and ALT increased significantly late in pregnancy or shortly after delivery. Vertical transmission was only seen in HBeAg-positive mothers with very high levels of viremia. The value of measuring HBV DNA in the pregnant woman to modify immunoprophylaxis to her infant needs further study.
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