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Frydén, Aril
Publications (10 of 25) 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., 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
Hedenstierna, M., Uhnoo, I., Aleman, S., Frydén, A., Norkrans, G. P., Eilard, A., . . . Weiland, O. (2011). DURABILITY OF SVR AND FIBROSIS IMPROVEMENT AFTER SOC TREATMENT FOR CHRONIC HCV-10 YEARS FOLLOW-UP in HEPATOLOGY, vol 54, issue , pp 839A-840A. In: HEPATOLOGY vol 54 (pp. 839A-840A). Wiley-Blackwell, 54
Open this publication in new window or tab >>DURABILITY OF SVR AND FIBROSIS IMPROVEMENT AFTER SOC TREATMENT FOR CHRONIC HCV-10 YEARS FOLLOW-UP in HEPATOLOGY, vol 54, issue , pp 839A-840A
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2011 (English)In: HEPATOLOGY vol 54, Wiley-Blackwell , 2011, Vol. 54, p. 839A-840AConference paper, Published paper (Refereed)
Abstract [en]

n/a

Place, publisher, year, edition, pages
Wiley-Blackwell, 2011
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-71785 (URN)000295578003238 ()
Available from: 2011-11-04 Created: 2011-11-04 Last updated: 2011-11-22
Bjornsson, E., Verbaan, H., Oksanen, A., Frydén, A., Johansson, J., Friberg, S., . . . Kalaitzakis, E. (2009). Health-related quality of life in patients with different stages of liver disease induced by hepatitis C. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 44(7), 878-887
Open this publication in new window or tab >>Health-related quality of life in patients with different stages of liver disease induced by hepatitis C
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2009 (English)In: SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, ISSN 0036-5521, Vol. 44, no 7, p. 878-887Article in journal (Refereed) Published
Abstract [en]

Objective. Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. Material and methods. Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. Results. The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (Pandlt;0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p andlt;0.05) and lower SF-36 physical component summary (PCS) scores (p andlt;0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis. Conclusions. Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.

Keywords
Hepatitis C, liver, liver cirrhosis, quality of life
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-19888 (URN)10.1080/00365520902898135 (DOI)
Available from: 2009-08-14 Created: 2009-08-14 Last updated: 2009-12-08
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
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
Dalgard, O., Bjøro, K., Ring-Larsen, H., Bjornsson, E., Holberg-Petersen, M., Skovlund, E., . . . Verbaan, H. (2008). Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. Hepatology, 47(1), 35-42
Open this publication in new window or tab >>Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response
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2008 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 47, no 1, p. 35-42Article in journal (Refereed) Published
Abstract [en]

A recent nonrandomized pilot trial showed that hepatitis C virus (HCV) patients with genotype 2/3 and rapid virological response (RVR) had a 90% sustained virological response (SVR) rate after 14 weeks of treatment. We aimed to assess this concept in a randomized controlled trial. In the trial, 428 treatment-naïve HCV RNA–positive patients with genotype 2 or 3 were enrolled. Patients with RVR were randomized to 14 (group A) or 24 (group B) weeks of treatment. Patients were treated with pegylated interferon α-2b (1.5 μg/kg) subcutaneously weekly and ribavirin (800-1400 mg) orally daily. The noninferiority margin was set to be 10% between the two groups with a one-sided 2.5% significance level. RVR was obtained in 302 of 428 (71%), and 298 of these were randomized to group A (n = 148) or group B (n = 150). In the intention-to-treat analysis, SVR rates were 120 of 148 (81.1%) in group A and 136 of 150 (90.7%) in group B (difference, 9.6%; 95% confidence interval, 1.7-17.7). Among patients with an HCV RNA test 24 weeks after the end of treatment, 120 of 139 (86.3%) patients in group A achieved SVR compared with 136 of 146 (93.2%) in group B (difference, 6.9%; 95% confidence interval, −0.1 to +13.9). Conclusion: We cannot formally claim that 14 weeks of treatment is noninferior to 24 weeks of treatment. However, the SVR rate after 14 weeks of treatment is high, and although longer treatment may give slightly better SVR, we believe economical savings and fewer side effects make it rational to treat patients with genotype 2 or 3 and RVR for only 14 weeks.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-47277 (URN)10.1002/hep.21975 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Follin, P. & Frydén, A. (2004). Tropiska virusinfektioner (3ed.). In: Iwarson-Norrby (Ed.), Infektionsmedicin: epidemiologi, klinik, terapi (pp. 395-408). Säve Förlag
Open this publication in new window or tab >>Tropiska virusinfektioner
2004 (Swedish)In: Infektionsmedicin: epidemiologi, klinik, terapi / [ed] Iwarson-Norrby, Säve Förlag , 2004, 3, p. 395-408Chapter in book (Other academic)
Abstract [sv]

Denna klassiska lärobok kom 2011 ut i sin 5:e, omarbetade upplaga. Boken innehåller 28 kapitel, vilka täcker hela infektionspanoramat, från influensa till AIDS. Samtliga författare är läkare och flertalet universitetslärare. Den innehåller även 16 sidor färgplanscher med fotoillustrationer av olika sjukdomar. Boken är avsedd att användas i undervisningen av blivande läkare och som uppslagsbok i sjukvården

Place, publisher, year, edition, pages
Säve Förlag, 2004 Edition: 3
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-33048 (URN)19011 (Local ID)91-972689-7-6 (ISBN)978-9-1972-6897-4 (ISBN)19011 (Archive number)19011 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2013-10-23Bibliographically approved
Uhnoo, I., Linde, A., Pauksens, K., Lindberg, A., Eriksson, M., Norrby, R., . . . Zweygberg, W. B. (2003). Treatment and prevention of influenza: Swedish recommendations. Scandinavian Journal of Infectious Diseases, 35(1)
Open this publication in new window or tab >>Treatment and prevention of influenza: Swedish recommendations
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2003 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 35, no 1Article in journal (Refereed) Published
Abstract [en]

The introduction of the 2 neuraminidase inhibitors (NAIs) zanamivir and oseltamivir has offered new options for the prevention and treatment of influenza. This article summarizes a Swedish consensus guidance document on the rational use of antiviral drugs in the management of influenza virus infections. Vaccination remains the cornerstone for influenza prophylaxis. Target groups for the annual vaccination programme are the 'at-risk' individuals, i.e. elderly patients (= 65 y) and patients with chronic pulmonary disease or cardiovascular disease or other chronic diseases predisposing for a complicated course of influenza. Antiviral drugs are not a substitute for influenza vaccination, but could be used as adjuncts. Currently, 3 drugs have been approved for the treatment of influenza, including zanamivir and oseltamivir and the M2 inhibitor amantadin. Amantadin has come to very limited use, has recently been withdrawn from the Swedish market and is available only on a named patient basis. Compared with amantadin, the NAIs have clear advantages because of their broader anti-influenza activity against both type A and B, improved safety profiles and low potential for inducing drug resistance. The NAIs are therefore recommended as first options in the treatment of influenza. Oseltamivir can be taken orally, whereas zanamivir is for oral inhalation. Limited in vitro and in vivo data suggest that oseltamivir is less potent against influenza B, whereas zanamivir seems equally effective against influenza A and B. In influenza-positive healthy adults and children, treated within 48 h after symptom onset, the NAIs shorten the duration of illness by about 1 d. No significant effect on the duration of symptoms has been documented in treated at-risk patients with influenza. Owing to their limited therapeutic benefit, general use of the NAIs in the treatment of influenza is not recommended, but they can be advocated on an individualized basis for patients with severe influenza who can start therapy within 48 h of the onset of symptoms. Zanamivir is the preferred choice in a confirmed influenza B epidemic. For prevention of influenza, 2 drugs are approved, oseltamivir in adults above 12 y old and amantadin in people above 10 y old. The 70-90% protective efficacy of oseltamivir for household postexposure prophylaxis and for seasonal prophylaxis is comparable to that reported for amantadin. Oseltamivir is the preferred drug for prophylactic use. Chemoprophylaxis is targeted at high-risk groups and should be considered on a case-by-case basis depending on the circumstances and the population requiring protection. A broader preventive use of oseltamivir can be advocated in at-risk groups during seasons when there is a poor antigenic match between the epidemic strains and the vaccine strains. Oseltamivir prophylaxis is otherwise recommended for patients unable to be vaccinated and for families exposed to influenza which include a member of the at-risk groups. In high-risk hospital units and in institutions caring for the elderly, oseltamivir prophylaxis, in combination with vaccination, can be recommended as measures to control an influenza outbreak.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-46695 (URN)10.1080/0036554021000026999 (DOI)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
Nayeri, F., Brudin, L., Darelid, J., Nilsson, I., Frydén, A., Söderström, C. & Forsberg, P. (2002). Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia. Scandinavian Journal of Infectious Diseases, 34(7), 500-504
Open this publication in new window or tab >>Hepatocyte growth factor may act as an early therapeutic predictor in pneumonia
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2002 (English)In: Scandinavian Journal of Infectious Diseases, ISSN 0036-5548, E-ISSN 1651-1980, Vol. 34, no 7, p. 500-504Article in journal (Refereed) Published
Abstract [en]

High serum levels of hepatocyte growth factor (HGF) may reflect the regenerative effect and enhanced local and systemic production of this cytokine after organ injuries. The possibility of using serial serum HGF values in order to predict the results of therapy for pneumonia was investigated in this study. In a prospective multicenter study we investigated the serum levels of HGF and CRP before and within 48 h after treatment in 70 patients with pneumonia. Serum levels of HGF before treatment were significantly higher than the HGF levels of a normal population (p < 0.0001). Within 48 h serum HGF levels had decreased significantly in those patients who ultimately responded to the initial antibiotic therapy (p < 0.0001). Serum HGF levels at 48 h were unchanged or increased in cases in whom the initial therapy was ineffective and had to be changed. CRP and HGF levels were significantly correlated. Using multivariate logistic regression analysis it was found that individual changes in acute serum HGF levels and serum HGF levels obtained within 48 h could predict the results of therapy at least as significantly (p < 0.003) as CRP (p = 0.05), although CRP levels were known and used by the physician to decide whether or not to change the initial therapy. We conclude that serial control of serum HGF levels can be used as an early indicator to predict the results of therapy during treatment of pneumonia.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-26409 (URN)10.1080/00365540110080890 (DOI)10950 (Local ID)10950 (Archive number)10950 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically approved
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