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Nasr, P., Fredrikson, M., Ekstedt, M. & Kechagias, S. (2020). The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.. Liver international (Print)
Open this publication in new window or tab >>The Amount of Liver Fat Predicts Mortality and Development of Type 2 Diabetes in Non-alcoholic Fatty Liver Disease.
2020 (English)In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231Article in journal (Refereed) Epub ahead of print
Abstract [en]

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is a risk factor for development of type 2 diabetes mellitus (T2DM). We aimed to evaluate whether conventional histological grading of steatosis and accurate quantification of fat content in liver biopsies using stereological point counting (SPC) can predict mortality and future development of T2DM in NAFLD patients.

METHODS: 129 patients with biopsy proven NAFLD, enrolled between 1988 and 1992, were re-evaluated on two occasions, after 13.7 (±1.5) and 23.2 (±6.8) years. In patients accepting to undergo the procedure, repeat liver biopsies were performed on each follow-up and were evaluated with conventional histopathological methodology and SPC.

RESULTS: Of the 106 patients without T2DM at baseline, 66 (62%) developed T2DM during a mean follow-up of 23.2 (± 6.8) years. Steatosis grade and liver fat measured with SPC independently (adjusted for age, BMI, fibrosis stage) predicted development of T2DM with an aHR of 1.60 per grade and 1.03 for each SPC percentage increase, respectively. Overall mortality and development of T2DM was more common in patients with grade 3 steatosis compared to lower grades of steatosis. Liver fat measured with SPC was significant for overall mortality (aHR 1.04). In patients that underwent repeat biopsy, reduction of liver fat measured with SPC was associated with decreased risk of developing T2DM (aHR 0.91 for each SPC percentage decrease).

CONCLUSION: Steatosis grade and liver fat measured with SPC predict mortality and the risk of developing T2DM in NAFLD. Reduction of liver fat decreases the risk of developing T2DM.

Place, publisher, year, edition, pages
John Wiley & Sons, 2020
Keywords
Stereological point count (SPC), hepatic steatosis, quantitative steatosis
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-163934 (URN)10.1111/liv.14414 (DOI)32087038 (PubMedID)
Available from: 2020-02-27 Created: 2020-02-27 Last updated: 2020-03-30Bibliographically approved
Dahlström, U., Kechagias, S. & Stenke, L. (Eds.). (2018). Internmedicin (6ed.). Stockholm: Liber
Open this publication in new window or tab >>Internmedicin
2018 (English)Collection (editor) (Other academic)
Alternative title[sv]
Med6
Abstract [sv]

Internmedicin beskriver uppkomstmekanismer, förlopp och medicinsk handläggning av den stora grupp sjukdomar som involverar kroppens centrala organsystem, inklusive hjärta-lungor-cirkulation, mage-tarm-lever, benmärg-blod, njurar, rörelseorgan och hormonsekretion.

Internmedicin utkom första gången 1978 och har sedan dess varit en uppskattad kunskapskälla för medicinstuderande under hela utbildningen liksom en oumbärlig uppslagsbok för kliniskt verksamma läkare. I denna sjätte reviderade upplaga är en majoritet av kapitlen nyskrivna eller grundligt uppdaterade. Som tidigare utgörs författarlistan av Sveriges ledande kliniska specialister och forskare inom sina respektive områden. Varje sjukdomstillstånd beskrivs detaljerat med uppgifter om bland annat etiologi, symtom, utredning och behandling. Framställningen är rikt illustrerad, och i varje kapitel belyser man den centrala handläggningen med kliniska patientfall.

Place, publisher, year, edition, pages
Stockholm: Liber, 2018. p. 1046 Edition: 6
Keywords
Internmedicin
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-163148 (URN)9789147113262 (ISBN)
Available from: 2020-01-16 Created: 2020-01-16 Last updated: 2020-01-31Bibliographically approved
Kechagias, S. (2018). Internmedicin: en introduktion (6ed.). In: Ulf Dahlström, Stergios Kechagias, Leif Stenke (Ed.), Internmedicin: (pp. 15-16). Stockholm: Liber, Sidorna 15-16
Open this publication in new window or tab >>Internmedicin: en introduktion
2018 (English)In: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias, Leif Stenke, Stockholm: Liber, 2018, 6, Vol. Sidorna 15-16, p. 15-16Chapter in book (Other academic)
Place, publisher, year, edition, pages
Stockholm: Liber, 2018 Edition: 6
Keywords
Internmedicin
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-163166 (URN)9789147113262 (ISBN)
Available from: 2020-01-20 Created: 2020-01-20 Last updated: 2020-01-21Bibliographically approved
Kechagias, S. (2018). Leversjukdomar (6ed.). In: Ulf Dahlström, Stergios Kechagias, Leif Stenke (Ed.), Internmedicin: (pp. 847-890). Stockholm: Liber, Sidorna 847-890
Open this publication in new window or tab >>Leversjukdomar
2018 (Swedish)In: Internmedicin / [ed] Ulf Dahlström, Stergios Kechagias, Leif Stenke, Stockholm: Liber, 2018, 6, Vol. Sidorna 847-890, p. 847-890Chapter in book (Other academic)
Place, publisher, year, edition, pages
Stockholm: Liber, 2018 Edition: 6
Keywords
Lever
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-163179 (URN)9789147113262 (ISBN)
Available from: 2020-01-21 Created: 2020-01-21 Last updated: 2020-01-21Bibliographically approved
Nasr, P., Hilliges, A., Thorelius, L., Kechagias, S. & Ekstedt, M. (2016). Contrast-enhanced ultrasonography could be a non-invasive method for differentiating none or mild from severe fibrosis in patients with biopsy proven non-alcoholic fatty liver disease. Scandinavian Journal of Gastroenterology, 51(9), 1126-1132
Open this publication in new window or tab >>Contrast-enhanced ultrasonography could be a non-invasive method for differentiating none or mild from severe fibrosis in patients with biopsy proven non-alcoholic fatty liver disease
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2016 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 9, p. 1126-1132Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: The gold standard for diagnosing fibrosis stage in non-alcoholic fatty liver disease (NAFLD) is liver biopsy. The aim of this study was to determine whether contrast-enhanced ultrasonography (CEUS) with transit time measurements could be a non-invasive alternative for differentiating none or mild from severe fibrosis in NAFLD patients. Various serum markers and clinical variables were also evaluated.

MATERIALS AND METHODS: Fifty-eight patients with NAFLD underwent CEUS prior to liver biopsy. All patients were also evaluated according to the Göteborg University Cirrhosis Index (GUCI), the AST-Platelet Ratio Index (APRI), the NAFLD fibrosis score, and the FIB-4 and BARD score.

RESULTS: The hepatic vein arrival time (HV) was shorter in patients with severe fibrosis (25.9 ± 4.8 vs 29.5 ± 4.7 s, p = 0.023), and the difference between the hepatic and portal vein (ΔHV-PV) was shorter (2.3 ± 2.8 vs 6.4 ± 2.8 s, p < 0.0001) while the difference in arrival time between the portal vein and hepatic artery (ΔPV-HA) arrival time was significantly longer (6.0 ± 2.2 vs 3.6 ± 1.6 s, p < 0.0001). The area under receiver operating characteristics curve values for HV, ΔHV-PV and ΔPV-HA to separate none or mild from severe fibrosis was 0.71, 0.83 and 0.84, respectively. The corresponding figures for GUCI, APRI, NAFLD fibrosis score, FIB-4 and BARD score were 0.93, 0.92, 0.86, 0.90 and 0.77, respectively.

CONCLUSIONS: CEUS and non-invasive scoring systems could exclude severe fibrosis in NAFLD patients.

Place, publisher, year, edition, pages
Taylor & Francis, 2016
Keywords
Contrast-enhanced ultrasonography, fibrosis, fibrosis scores, non-alcoholic fatty liver disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-129954 (URN)10.3109/00365521.2016.1172336 (DOI)000381406800018 ()27161854 (PubMedID)
Note

Funding agencies: Research Council of Southeast Sweden [F2004-303]; ALF Grants, Region Ostergotland

Available from: 2016-07-02 Created: 2016-07-02 Last updated: 2017-11-28Bibliographically approved
Rendek, Z., Falk, M., Grodzinsky, E., Wahlin, K., Kechagias, S., Svernlöv, R. & Hjortswang, H. (2016). Effect of oral diclofenac intake on faecal calprotectin. Scandinavian Journal of Gastroenterology, 51(1), 28-32
Open this publication in new window or tab >>Effect of oral diclofenac intake on faecal calprotectin
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2016 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 51, no 1, p. 28-32Article in journal (Refereed) Published
Abstract [en]

Background. NSAIDs are a known source of increased faecal calprotectin (FC) levels. Currently, there is a lack of knowledge about how long it takes for an increased FC level to return to normal after NSAID intake. Objective. The aim was to investigate how oral diclofenac intake affects FC levels and assess how long it takes for an increased FC level to return to normal after oral diclofenac intake. Material and methods. Thirty healthy volunteers received diclofenac 50 mg three times daily for 14 days. Participants provided a stool sample on Days 0, 2, 4, 7, 14 during intake and Days 17, 21, 28 after discontinuation. FC levels were then followed at 7-day intervals until normalization. Results. During diclofenac intake, eight participants (27%) had FC levels exceeding the upper limit of normal (median, 76 mu g/g; range, 60-958 mu g/g), corresponding to 8.3% of measurements. FC was not constantly increased and became normal in most participants during diclofenac intake. FC levels were on average significantly higher during intake (M = 9.5, interquartile range (IQR) = 13.4) than on baseline (M = 7.5, IQR = 0.0), p = 0.003. After discontinuation, two participants had increased FC on Days 17 and 21, respectively. No significant differences in FC levels were found between baseline and measurements after discontinuation. Two weeks after discontinuation, all participants had normal FC levels. Conclusions. Short-term oral diclofenac intake is associated with increased FC levels. However, the likelihood of an increased test result is low. Our results suggest that 2 weeks of diclofenac withdrawal is sufficient to get an uninfluenced FC test result.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2016
Keywords
intestinal inflammation; proton pump inhibitors; NSAIDs; non-steroidal anti-inflammatory agents; diclofenac; calprotectin
National Category
Physiology Public Health, Global Health, Social Medicine and Epidemiology
Identifiers
urn:nbn:se:liu:diva-127586 (URN)10.3109/00365521.2015.1066421 (DOI)000373621900005 ()26200803 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland, Sweden

Available from: 2016-05-03 Created: 2016-05-03 Last updated: 2018-03-22
Hagström, H., Nasr, P., Bottai, M., Ekstedt, M., Kechagias, S., Hultcrantz, R. & Stål, P. (2016). Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up. Liver international (Print), 36(11), 1688-1695
Open this publication in new window or tab >>Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up
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2016 (English)In: Liver international (Print), ISSN 1478-3223, E-ISSN 1478-3231, Vol. 36, no 11, p. 1688-1695Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: High levels of ferritin in patients with non-alcoholic fatty liver disease (NAFLD) are associated with significant fibrosis and higher NAFLD activity score (NAS). It is unclear if this association has an impact on mortality. We investigated if high levels of ferritin, with or without iron overload, were associated with an increased mortality in NAFLD.

METHODS: We included 222 patients between 1979 and 2009 with biopsy-proven NAFLD and available serum ferritin concentrations. The cohort was divided into "high" (n = 89) and "normal" (n = 133) ferritin values, using a cut-point of 350 μg/L in males, and 150 μg/L in females, and stratified upon iron overload status. Data on mortality was obtained from a national, population based register. Poisson regression was used to estimate hazard ratios for mortality. The estimates were adjusted for age at biopsy, sex, smoking, BMI, diabetes, hypertension, cardiovascular disease and fibrosis stage at the time of biopsy.

RESULTS: The median follow-up time was 15.6 years (range: 0.5-34.2). Patients with high ferritin had more advanced fibrosis and higher NAS than patients with normal ferritin (p < 0.05). Fifteen years after diagnosis, and after adjusting for confounders, the high-ferritin group showed an increasingly higher mortality that was statistically significant (Hazard ratio = 1.10 per year, 95% Confidence interval 1.01-1.21, p < 0.05). There was no difference in mortality between patients with different iron overload patterns.

CONCLUSIONS: High levels of ferritin are associated with a long-term increased risk of death. This article is protected by copyright. All rights reserved.

Place, publisher, year, edition, pages
John Wiley & Sons, 2016
Keywords
ferritin;fibrosis, long-term outcome, mortality, NAFLD activity score, non-alcoholic fatty liver disease
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-129955 (URN)10.1111/liv.13144 (DOI)000385863400016 ()27064133 (PubMedID)
Note

Funding agencies:Stockholm County Council (ALF projects from the Swedish Society of Medicine [20140329, 20150403]; Ruth and Richard Julins Foundation; Medical Research Council of Southeast Sweden [311151]; ALF grants, Region Ostergotland, Sweden

Available from: 2016-07-02 Created: 2016-07-02 Last updated: 2017-11-28Bibliographically approved
Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stal, P., Kechagias, S. & Hultcrantz, R. (2016). Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY [Letter to the editor]. Hepatology, 64(1), 310-311
Open this publication in new window or tab >>Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY
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2016 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 64, no 1, p. 310-311Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
Wiley-Blackwell, 2016
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-124403 (URN)10.1002/hep.28314 (DOI)000379233400041 ()26517017 (PubMedID)
Available from: 2016-01-28 Created: 2016-01-28 Last updated: 2017-11-30
Forsgren, M., Norén, B., Kihlberg, J., Dahlqvist Leinhard, O., Kechagias, S. & Lundberg, P. (2015). Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences. European Journal of Radiology Open, 2, 66-70
Open this publication in new window or tab >>Comparing hepatic 2D and 3D magnetic resonance elastography methods in a clinical setting – Initial experiences
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2015 (English)In: European Journal of Radiology Open, E-ISSN 2352-0477, Vol. 2, p. 66-70Article in journal (Refereed) Published
Abstract [en]

Purpose

Continuous monitoring of liver fibrosis progression in patients is not feasible with the current diagnostic golden standard (needle biopsy). Recently, magnetic resonance elastography (MRE) has emerged as a promising method for such continuous monitoring. Since there are different MRE methods that could be used in a clinical setting there is a need to investigate whether measurements produced by these MRE methods are comparable. Hence, the purpose of this pilot study was to evaluate whether the measurements of the viscoelastic properties produced by 2D (stiffness) and 3D (elasticity and ‘Gabs,Elastic’) MRE are comparable.

Materials and methods

Seven patients with diffuse or suspect diffuse liver disease were examined in the same day with the two MRE methods. 2D MRE was performed using an acoustic passive transducer, with a 1.5 T GE 450 W MR system. 3D MRE was performed using an electromagnetic active transducer, with a 1.5 T Philips Achieva MR system. Finally, mean viscoelastic values were extracted from the same anatomical region for both methods by an experienced radiologist.

Results

Stiffness correlated well with the elasticity, R2 = 0.96 (P < 0.001; slope = 1.08, intercept = 0.61 kPa), as well as with ‘Gabs,ElasticR2 = 0.96 (P < 0.001; slope = 0.95, intercept = 0.28 kPa).

Conclusion

This pilot study shows that different MRE methods can produce comparable measurements of the viscoelastic properties of the liver. The existence of such comparable measurements is important, both from a clinical as well as a research perspective, since it allows for equipment-independent monitoring of disease progression.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Liver; Rheology; Elastography; Fibrosis; MRE; MRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-119848 (URN)10.1016/j.ejro.2015.04.001 (DOI)
Available from: 2015-06-26 Created: 2015-06-26 Last updated: 2019-06-14Bibliographically approved
Andersson, T., Romu, T., Karlsson, A., Norén, B., Forsgren, M., Smedby, Ö., . . . Dahlqvist Leinhard, O. (2015). Consistent intensity inhomogeneity correction in water–fat MRI. Journal of Magnetic Resonance Imaging, 42(2), 468-476
Open this publication in new window or tab >>Consistent intensity inhomogeneity correction in water–fat MRI
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2015 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 42, no 2, p. 468-476Article in journal (Refereed) Published
Abstract [en]

PURPOSE:

To quantitatively and qualitatively evaluate the water-signal performance of the consistent intensity inhomogeneity correction (CIIC) method to correct for intensity inhomogeneities METHODS: Water-fat volumes were acquired using 1.5 Tesla (T) and 3.0T symmetrically sampled 2-point Dixon three-dimensional MRI. Two datasets: (i) 10 muscle tissue regions of interest (ROIs) from 10 subjects acquired with both 1.5T and 3.0T whole-body MRI. (ii) Seven liver tissue ROIs from 36 patients imaged using 1.5T MRI at six time points after Gd-EOB-DTPA injection. The performance of CIIC was evaluated quantitatively by analyzing its impact on the dispersion and bias of the water image ROI intensities, and qualitatively using side-by-side image comparisons.

RESULTS:

CIIC significantly ( P1.5T≤2.3×10-4,P3.0T≤1.0×10-6) decreased the nonphysiological intensity variance while preserving the average intensity levels. The side-by-side comparisons showed improved intensity consistency ( Pint⁡≤10-6) while not introducing artifacts ( Part=0.024) nor changed appearances ( Papp≤10-6).

CONCLUSION:

CIIC improves the spatiotemporal intensity consistency in regions of a homogenous tissue type. J. Magn. Reson. Imaging 2014.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015
Keywords
water–fat imaging;Dixon imaging;inhomogeneity correction;intensity correction;water;fat quantification
National Category
Medical Image Processing Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-112129 (URN)10.1002/jmri.24778 (DOI)000358258600026 ()25355066 (PubMedID)
Note

Funding:

Financial support from the Swedish Research Council (VR/M 2007-2884), the Research Council of Southeast Sweden (FORSS 12621), Linkoping University, Lions Research Foundation in Linkoping, Linkoping University Hospital Research Foundations and the County Council of Ostergotland is gratefully acknowledged.

Available from: 2014-11-16 Created: 2014-11-16 Last updated: 2019-06-14
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ORCID iD: ORCID iD iconorcid.org/0000-0001-7614-739x

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