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Kechagias, Stergios
Publications (10 of 58) Show all publications
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
Ekstedt, M., Hagström, H., Nasr, P., Fredrikson, M., Stål, P., Kechagias, S. & Hultcrantz, R. (2015). Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology, 61(5), 1547-1554
Open this publication in new window or tab >>Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up
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2015 (English)In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 61, no 5, p. 1547-1554Article in journal (Refereed) Published
Abstract [en]

Background and rationale for the study: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, strongly associated with insulin resistance and the metabolic syndrome. Nonalcoholic steatohepatitis, i.e. fatty liver accompanied by necroinflammatory changes, is mostly defined by the NAFLD activity score (NAS). The aim of the current study was to determine disease-specific mortality in NAFLD, and evaluate the NAS and fibrosis stage as prognostic markers for overall and disease-specific mortality. Methods: In a cohort study, data from 229 well-characterized patients with biopsy-proven NAFLD were collected. Mean follow-up was 26.4 (± 5.6, range 6-33) years. A reference population was obtained from the National Registry of Population, and information on time and cause of death were obtained from the Registry of Causes of Death. Main results: NAFLD patients had an increased mortality compared with the reference population (HR 1.29, CI 1.04-1.59, p=0.020), with increased risk of cardiovascular disease (HR 1.55, CI 1.11-2.15, p=0.01), hepatocellular carcinoma (HR 6.55, CI 2.14-20.03, p=0.001), infectious disease (HR 2.71, CI 1.02-7.26, p=0.046), and cirrhosis (HR 3.2, CI 1.05-9.81, p=0.041). Overall mortality was not increased in patients with NAS 5-8 and fibrosis stage 0-2 (HR 1.41, CI 0.97-2.06, p=0.07), whereas patients with fibrosis stage 3-4, irrespective of NAS, had increased mortality (HR 3.3, CI 2.27-4.76, p<0.001). Conclusions: NAFLD patients have increased risk of death, with a high risk of death from cardiovascular disease and liver-related disease. The NAS was not able to predict overall mortality, whereas fibrosis stage predicted both overall and disease-specific mortality.

Place, publisher, year, edition, pages
John Wiley & Sons, 2015
Keywords
NAFLD activity score; cohort study; fatty liver; liver fibrosis; mortality
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-112707 (URN)10.1002/hep.27368 (DOI)000353233500015 ()25125077 (PubMedID)
Available from: 2014-12-08 Created: 2014-12-08 Last updated: 2017-12-05
Kechagias, S., Dernroth, D. N., Blomgren, A., Hansson, T., Isaksson, A., Walther, L., . . . Nystrom, F. H. (2015). Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.. Alcohol and Alcoholism, 50(4), 399-406
Open this publication in new window or tab >>Phosphatidylethanol Compared with Other Blood Tests as a Biomarker of Moderate Alcohol Consumption in Healthy Volunteers: A Prospective Randomized Study.
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2015 (English)In: Alcohol and Alcoholism, ISSN 0735-0414, E-ISSN 1464-3502, Vol. 50, no 4, p. 399-406Article in journal (Refereed) Published
Abstract [en]

AIM: It is generally agreed that traditional alcohol biomarkers lack in sensitivity to detect hazardous alcohol consumption. The present study was undertaken to evaluate the ability of phosphatidylethanol (PEth) and traditional alcohol markers to detect moderate alcohol consumption and to distinguish between moderate alcohol consumption and abstinence.

METHODS: Forty-four subjects, 32 females and 12 males, were included in the study. They were randomized to alcohol abstention or to alcohol consumption. Female participants consumed 150 ml of red wine (equivalent to 16 g of alcohol) per 24 h and the male participants double the amount. The study lasted for 3 months. Blood samples were drawn at the start and at the end of the study period. Blood samples were analysed for PEth, carbohydrate-deficient transferrin (CDT), mean corpuscular volume (MCV), γ-glutamyltransferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

RESULTS: ROC curves for the various biochemical markers were plotted in order to assess their ability to discriminate between abstention and moderate daily consumption of alcohol. PEth and CDT were the only markers with AUROCs significantly higher than 0.5, and PEth was detected in all participants randomized to alcohol consumption.

CONCLUSION: PEth was the only marker that could detect moderate intake and the present results also indicate that PEth probably can distinguish moderate alcohol consumption from abstinence.

National Category
Substance Abuse
Identifiers
urn:nbn:se:liu:diva-119707 (URN)10.1093/alcalc/agv038 (DOI)000357867100005 ()25882743 (PubMedID)
Available from: 2015-06-24 Created: 2015-06-24 Last updated: 2017-12-04
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
Norén, B., Dahlström, N., Forsgren, M., Dahlqvist Leinhard, O., Kechagias, S., Almer, S., . . . Lundberg, P. (2015). Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease – a biopsy-controlled prospective study. European Journal of Radiology Open, 2, 19-25
Open this publication in new window or tab >>Visual assessment of biliary excretion of Gd-EOB-DTPA in patients with suspected diffuse liver disease – a biopsy-controlled prospective study
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2015 (English)In: European Journal of Radiology Open, ISSN 2352-0477, Vol. 2, p. 19-25Article in journal (Refereed) Published
Abstract [en]

Objectives: To qualitatively evaluate late dynamic contrast phases, 10, 20 and 30 min, after administration of Gd-EOB-DTPA with regard to biliary excretion in patients presenting with elevated liver enzymes without any clinical signs of cirrhosis or hepatic decompensation and to compare the visual assessment of contrast agent excretion with histo-pathological fibrosis stage, contrast uptake parameters and blood tests.

Methods: 29 patients were prospectively examined using 1.5-T MRI. The visually assessed presence (1) or absence (0) of contrast agent for each of five anatomical regions in randomly reviewed time-series was summarised on a four grade scale. The scores, including a total visual score, were related to the histo-pathological findings, the quantitative contrast agent uptake parameters and blood tests

Results: No relationship between the fibrosis grade or contrast uptake parameters expressed as KHep or LSC_N could be established. A negative correlation between the visual assessment and ALP was found. Comparing a sub-group of cholestatic patients with fibrosis score and Gd-EOB-DTPAdynamic parameters did not add any additional significant correlation.

Conclusions: In this prospective study with a limited number of patients we were not able to demonstrate a correlation between visually assessed biliary excretion of Gd-EOB-DTPA and  histo-pathological or contrast uptake parameters.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Gd-EOB-­DTPA, Dynamic contrast enhanced MRI, Liver, Bile, Excretion
National Category
Radiology, Nuclear Medicine and Medical Imaging Physical Chemistry
Identifiers
urn:nbn:se:liu:diva-90159 (URN)10.1016/j.ejro.2014.12.004 (DOI)
Projects
NILB
Available from: 2013-03-20 Created: 2013-03-20 Last updated: 2019-06-14Bibliographically approved
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