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Hagström, H., Vessby, J., Ekstedt, M. & Shang, Y. (2024). 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical [Letter to the editor]. Journal of Hepatology, 80(2), e76-e77
Open this publication in new window or tab >>99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical
2024 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 80, no 2, p. e76-e77Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2024
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-200825 (URN)10.1016/j.jhep.2023.08.026 (DOI)001168775800001 ()37678723 (PubMedID)
Funder
Pfizer AB
Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2025-02-11
Jönsson, C., Bergram, M., Kechagias, S., Nasr, P. & Ekstedt, M. (2024). Activin A levels in metabolic dysfunction-associated steatotic liver disease associates with fibrosis and the PNPLA3 I148M variant. Scandinavian Journal of Gastroenterology, 59(6), 737-741
Open this publication in new window or tab >>Activin A levels in metabolic dysfunction-associated steatotic liver disease associates with fibrosis and the PNPLA3 I148M variant
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2024 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 59, no 6, p. 737-741Article in journal (Refereed) Published
Abstract [en]

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition worldwide. There is an urgent need to develop new biomarkers to assess disease severity and to define patients with a progressive phenotype. Activin A is a new promising biomarker with conflicting results about liver fibrosis. In this study we investigate levels of Activin A in patients with biopsy proven MASLD. We assess levels of Activin A in regard to fibrosis stage and genetic variant I148M in the patatin-like phospholipase domain-containing protein 3 (PNPLA3). Methods: Activin A levels were assessed in plasma samples from patients with biopsy-proven MASLD in a cross-sectional study. All patients were clinically evaluated and the PNPLA3 I148M genotype of the cohort was assessed. Findings41 patients were included and 27% of these had advanced fibrosis. In MASLD patients with advanced fibrosis, Activin A levels was higher (p < 0.001) and could classify advanced fibrosis with an AUROC for activin A of 0.836 (p < 0.001). Patients homozygous for PNPLA3 I148M G/G had higher levels of activin A than non-homozygotes (p = 0.027). Conclusions: Circulating activin A levels were associated with advanced fibrosis and could be a potential blood biomarker for identifying advanced fibrosis in MASLD. Patients with the risk genotype PNPLA3 I148M G/G had higher levels of activin A proposing activin A as a contributor of the transition from simple steatosis to a fibrotic phenotype.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2024
Keywords
NAFLD; biomarkers; NIT; liver biopsy
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-202487 (URN)10.1080/00365521.2024.2334804 (DOI)001195714400001 ()38563432 (PubMedID)2-s2.0-85189778753 (Scopus ID)
Note

Funding Agencies|ALF Grants; Region Ostergotland; Swedish Medical Society; Bengt Ihre Foundation; Ruth and Richard Julin Foundation; Wallenberg Centre for Molecular Medicine, Linkoping University

Available from: 2024-04-15 Created: 2024-04-15 Last updated: 2025-03-24Bibliographically approved
Vacca, M., Kamzolas, I., Harder, L. M., Oakley, F., Trautwein, C., Hatting, M., . . . Brass, C. (2024). An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD). Nature Metabolism, 6(6), 1178-+
Open this publication in new window or tab >>An unbiased ranking of murine dietary models based on their proximity to human metabolic dysfunction-associated steatotic liver disease (MASLD)
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2024 (English)In: Nature Metabolism, E-ISSN 2522-5812, Vol. 6, no 6, p. 1178-+Article in journal (Refereed) Published
Abstract [en]

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease, encompasses steatosis and metabolic dysfunction-associated steatohepatitis (MASH), leading to cirrhosis and hepatocellular carcinoma. Preclinical MASLD research is mainly performed in rodents; however, the model that best recapitulates human disease is yet to be defined. We conducted a wide-ranging retrospective review (metabolic phenotype, liver histopathology, transcriptome benchmarked against humans) of murine models (mostly male) and ranked them using an unbiased MASLD 'human proximity score' to define their metabolic relevance and ability to induce MASH-fibrosis. Here, we show that Western diets align closely with human MASH; high cholesterol content, extended study duration and/or genetic manipulation of disease-promoting pathways are required to intensify liver damage and accelerate significant (F2+) fibrosis development. Choline- deficient models rapidly induce MASH-fibrosis while showing relatively poor translatability. Our ranking of commonly used MASLD models, based on their proximity to human MASLD, helps with the selection of appropriate in vivo models to accelerate preclinical research.

Place, publisher, year, edition, pages
NATURE PORTFOLIO, 2024
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-209103 (URN)10.1038/s42255-024-01043-6 (DOI)001287307700001 ()38867022 (PubMedID)2-s2.0-85195930089 (Scopus ID)
Note

Funding Agencies|multi-center study aiming to evaluate NAFLD biomarkers; Innovative Medicines Initiative 2 (IMI2) Joint Undertaking [777377]; European Union's Horizon 2020 research and innovation program; European Federation of Pharmaceutical Industries and Associations (EFPIA); European Bioinformatics Institute (EMBL-EBI); EMBL-EBI; Medical Research Council (MRC); University of Bari [S06-miRNASH]; Foundation for Liver Research; Associazione Italiana Ricerca sul Cancro [IG2022, 27521]; Ministry of University and Research on Next Generation EU Funds [P202222FCC, H53D23009960001, DD MUR 1366, 01-09-2023, H93C22000630001, DD MUR 1550, CN00000041, H93C22000430007, H93C22000450007]; MRC Metabolic Diseases Unit [(MC_UU_00014/5)]; UK MRC program [MR/K0019494/1, MR/R023026/1]; Fundacao para a Ciencia e Tecnologia [PTDC/MED-FAR/3492/2021]; La Caixa Foundation [LCF/PR/HR21/52410028]; Newcastle NIHR Biomedical Research Centre; National Institutes of Health (NIH) [NIH R01 DK128289, NCI 5P30CA196521-08, R01 DK136016]

Available from: 2024-11-05 Created: 2024-11-05 Last updated: 2025-04-30
Edin, C., Ekstedt, M., Karlsson, M., Wegmann, B., Warntjes, M., Swahn, E., . . . Carlhäll, C.-J. (2024). Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis. European Radiology
Open this publication in new window or tab >>Liver fibrosis is associated with left ventricular remodeling: insight into the liver-heart axis
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2024 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084Article in journal (Refereed) Published
Abstract [en]

Objective: In non-alcoholic fatty liver disease (NAFLD), liver fibrosis is the strongest predictor of adverse outcomes. We sought to investigate the relationship between liver fibrosis and cardiac remodeling in participants from the general population using magnetic resonance imaging (MRI), as well as explore potential mechanistic pathways by analyzing circulating cardiovascular biomarkers.

Methods: In this cross-sectional study, we prospectively included participants with type 2 diabetes and individually matched controls from the SCAPIS (Swedish CArdioPulmonary bioImage Study) cohort in Linköping, Sweden. Between November 2017 and July 2018, participants underwent MRI at 1.5 Tesla for quantification of liver proton density fat fraction (spectroscopy), liver fibrosis (stiffness from elastography), left ventricular (LV) structure and function, as well as myocardial native T1 mapping. We analyzed 278 circulating cardiovascular biomarkers using a Bayesian statistica lapproach.

Results: In total, 92 participants were enrolled (mean age 59.5 ± 4.6 years, 32 women). The mean liver stiffness was 2.1 ± 0.4 kPa. 53 participants displayed hepatic steatosis. LV concentricity increased across quartiles of liver stiffness. Neither liver fat nor liver stiffness displayed any relationships to myocardial tissue characteristics (native T1). In a regression analysis, liver stiffness was related to increased LV concentricity. This association was independent of diabetes and liver fat (Beta = 0.26, p = 0.0053), but was attenuated (Beta = 0.17, p = 0.077) when also adjusting for circulating levels of interleukin-1 receptor type 2.

Conclusion: MRI reveals that liver fibrosis is associated to structural LV remodeling, in terms of increased concentricity, in participants from the general population. This relationship could involve the interleukin-1 signaling.

Place, publisher, year, edition, pages
Springer Science and Business Media LLC, 2024
Keywords
Interleukin-1, Non-alcoholic fatty liver disease, Type 2 diabetes, Elastography, Magnetic Resonance
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-203718 (URN)10.1007/s00330-024-10798-1 (DOI)001234017500001 ()38795131 (PubMedID)2-s2.0-85194375559 (Scopus ID)
Note

Funding Agencies|Swedish Research Council; Swedish Heart and Lung Foundation; ALF Grants Region OEstergoetland; Linkoeping University

Available from: 2024-05-27 Created: 2024-05-27 Last updated: 2025-04-09
Akbari, C., Dodd, M., Stål, P., Nasr, P., Ekstedt, M., Kechagias, S., . . . Shang, Y. (2024). Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD. JHEP Reports, 6(2), Article ID 100915.
Open this publication in new window or tab >>Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD
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2024 (English)In: JHEP Reports, E-ISSN 2589-5559, Vol. 6, no 2, article id 100915Article in journal (Refereed) Published
Abstract [en]

Background & aims: Long-term studies of the prognosis of NAFLD are scarce. Here, we investigated the risk of major adverse liver outcomes (MALO) in a large cohort of patients with NAFLD.

Methods: We conducted a cohort study with data from Swedish university hospitals. Patients (n = 1,260) with NAFLD without cirrhosis were diagnosed through biopsy or radiology, and had fibrosis estimated through vibration-controlled transient elastography, biopsy, or FIB-4 score between 1974 and 2020 and followed up through 2020. Each patient was matched on age, sex, and municipality with up to 10 reference individuals from the general population (n = 12,529). MALO were ascertained from Swedish national registers. The rate of events was estimated by Cox regression.

Results: MALO occurred in 111 (8.8%, incidence rate = 5.9/1,000 person-years) patients with NAFLD and 197 (1.6%, incidence rate = 1.0/1,000 person-years) reference individuals during a median follow up of 13 years. The rate of MALO was higher in patients with NAFLD (hazard ratio = 6.6; 95% CI = 5.2-8.5). The risk of MALO was highly associated with the stage of fibrosis at diagnosis. In the biopsy subcohort (72% of total sample), there was no difference in risk between patients with and without non-alcoholic steatohepatitis. The 20-year cumulative incidences of MALO were 2% for the reference population, 3% for patients with F0, and 35% for F3. Prognostic information from biopsy was comparable to FIB-4 (C-indices around 0.73 vs. 0.72 at 10 years).

Conclusions: This study provides updated information on the natural history of NAFLD, showing a high rate of progression to cirrhosis in F3 and a similar prognostic capacity of non-invasive tests to liver biopsy.

Impact and implications: Several implications for clinical care and future research may be noted based on these results. First, the risk estimates for cirrhosis development are important when communicating risk to patients and deciding on clinical monitoring and treatment. Estimates can also be used in updated health-economic evaluations, and for regulatory agencies. Second, our results again highlight the low predictive information obtained from ascertaining NASHstatus by histology and call for more objective means by which to define NASH. Such methods may include artificial intelligence-supported digital pathology. We highlight that NASH is most likely the causal factor for fibrosis progression in NAFLD, but the subjective definition makes the prognostic value of a histological NASH diagnosis of limited value. Third, the finding that prognostic information from biopsy and the very simple Fibrosis-4 score were comparable is important as it may lead to fewer biopsies and further move the field towards non-invasive means by which to define fibrosis and, importantly, use non-invasive tests as outcomes in clinical trials. However, all modalities had modest discriminatory capacity and new risk stratification systems are needed in NAFLD. Repeated measures of non-invasive scores may be a potential solution.

Place, publisher, year, edition, pages
Elsevier, 2024
Keywords
FIB-4; Fibrosis stage; Major adverse liver outcomes; NAFLD; NASH; Non-invasive; Prediction
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-200820 (URN)10.1016/j.jhepr.2023.100915 (DOI)001164198100001 ()38293684 (PubMedID)
Funder
Åke Wiberg FoundationKarolinska InstituteSwedish Research Council
Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2025-02-11
Yang, W., Ebrahimi, F., Romeo, S., Holmer, M., Vessby, J., Ekstedt, M., . . . Hagström, H. (2024). Risk of major adverse liver outcomes among first-degree relatives of individuals with MASLD. Liver international, 44(5), 1253-1264
Open this publication in new window or tab >>Risk of major adverse liver outcomes among first-degree relatives of individuals with MASLD
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2024 (English)In: Liver international, ISSN 1478-3223, E-ISSN 1478-3231, Vol. 44, no 5, p. 1253-1264Article in journal (Refereed) Published
Abstract [en]

Background & AimsPrevious studies have suggested an increased risk of major adverse liver outcomes (MALO) in relatives of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). However, granular and longitudinal evidence is lacking on the future risk of MALO among family members of individuals with MASLD.MethodsWe identified 3526 first-degree relatives (FDRs) and 11 079 general population comparators to 1328 patients with MASLD diagnosed between 1974 and 2021, with detailed clinical data, including liver histology in 71% of patients. MALO was defined through diagnostic coding for cirrhosis or its complications. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MALO among FDRs compared to general population comparators. Cumulative incidence accounting for competing risks was calculated.ResultsDuring a median follow-up of 13.4 years, there were 65 (2%, 1.12/1000 person-years) and 225 (2%, 1.26/1000 person-years) MALO events in FDRs and general population comparators respectively. After adjusting for demographic factors and comorbidities, FDRs were at no increased risk of MALO (aHR = 0.99, 95% CI: 0.74-1.33). Increased relative rates of MALOs were, however, observed in some subgroups, including parents, although absolute risk estimates were low and comparable to the general population.ConclusionsFDRs of patients with MASLD did not have a higher rate of incident MALO than the general population. Since the absolute risk of MALO in relatives of patients with MASLD was low, these results do not support systematic screening of MASLD-related fibrosis in relatives of patients with MASLD.

Place, publisher, year, edition, pages
WILEY, 2024
Keywords
first-degree relative; genetic risk; major adverse liver outcomes; metabolic dysfunction-associated steatotic liver disease
National Category
Other Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-201461 (URN)10.1111/liv.15874 (DOI)001169510000001 ()38385564 (PubMedID)2-s2.0-85186484472 (Scopus ID)
Available from: 2024-03-11 Created: 2024-03-11 Last updated: 2025-03-06Bibliographically approved
Vali, Y., Lee, J., Boursier, J., Petta, S., Wonders, K., Tiniakos, D., . . . Bossuyt, P. M. (2023). Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study. The Lancet Gastroenterology & Hepatology, 8(8), 714-725
Open this publication in new window or tab >>Biomarkers for staging fibrosis and non-alcoholic steatohepatitis in non-alcoholic fatty liver disease (the LITMUS project): a comparative diagnostic accuracy study
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2023 (English)In: The Lancet Gastroenterology & Hepatology, ISSN 2468-1253, Vol. 8, no 8, p. 714-725Article in journal (Refereed) Published
Abstract [en]

Background: The reference standard for detecting non-alcoholic steatohepatitis (NASH) and staging fibrosis—liver biopsy—is invasive and resource intensive. Non-invasive biomarkers are urgently needed, but few studies have compared these biomarkers in a single cohort. As part of the Liver Investigation: Testing Marker Utility in Steatohepatitis (LITMUS) project, we aimed to evaluate the diagnostic accuracy of 17 biomarkers and multimarker scores in detecting NASH and clinically significant fibrosis in patients with non-alcoholic fatty liver disease (NAFLD) and identify their optimal cutoffs as screening tests in clinical trial recruitment. Methods: This was a comparative diagnostic accuracy study in people with biopsy-confirmed NAFLD from 13 countries across Europe, recruited between Jan 6, 2010, and Dec 29, 2017, from the LITMUS metacohort of the prospective European NAFLD Registry. Adults (aged ≥18 years) with paired liver biopsy and serum samples were eligible; those with excessive alcohol consumption or evidence of other chronic liver diseases were excluded. The diagnostic accuracy of the biomarkers was expressed as the area under the receiver operating characteristic curve (AUC) with liver histology as the reference standard and compared with the Fibrosis-4 index for liver fibrosis (FIB-4) in the same subgroup. Target conditions were the presence of NASH with clinically significant fibrosis (ie, at-risk NASH; NAFLD Activity Score ≥4 and F≥2) or the presence of advanced fibrosis (F≥3), analysed in all participants with complete data. We identified thres holds for each biomarker for reducing the number of biopsy-based screen failures when recruiting people with both NASH and clinically significant fibrosis for future trials. Findings: Of 1430 participants with NAFLD in the LITMUS metacohort with serum samples, 966 (403 women and 563 men) were included after all exclusion criteria had been applied. 335 (35%) of 966 participants had biopsy-confirmed NASH and clinically significant fibrosis and 271 (28%) had advanced fibrosis. For people with NASH and clinically significant fibrosis, no single biomarker or multimarker score significantly reached the predefined AUC 0·80 acceptability threshold (AUCs ranging from 0·61 [95% CI 0·54–0·67] for FibroScan controlled attenuation parameter to 0·81 [0·75–0·86] for SomaSignal), with accuracy mostly similar to FIB-4. Regarding detection of advanced fibrosis, SomaSignal (AUC 0·90 [95% CI 0·86–0·94]), ADAPT (0·85 [0·81–0·89]), and FibroScan liver stiffness measurement (0·83 [0·80–0·86]) reached acceptable accuracy. With 11 of 17 markers, histological screen failure rates could be reduced to 33% in trials if only people who were marker positive had a biopsy for evaluating eligibility. The best screening performance for NASH and clinically significant fibrosis was observed for SomaSignal (number needed to test [NNT] to find one true positive was four [95% CI 4–5]), then ADAPT (six [5–7]), MACK-3 (seven [6–8]), and PRO-C3 (nine [7–11]). Interpretation: None of the single markers or multimarker scores achieved the predefined acceptable AUC for replacing biopsy in detecting people with both NASH and clinically significant fibrosis. However, several biomarkers could be applied in a prescreening strategy in clinical trial recruitment. The performance of promising markers will be further evaluated in the ongoing prospective LITMUS study cohort. Funding: The Innovative Medicines Initiative 2 Joint Undertaking. © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Place, publisher, year, edition, pages
Elsevier Ltd, 2023
Keywords
Adolescent; Adult; Biomarkers; Female; Fibrosis; Humans; Liver Cirrhosis; Male; Non-alcoholic Fatty Liver Disease; Prospective Studies; alanine aminotransferase; biological marker; triacylglycerol; biological marker; adult; alcohol consumption; area under the curve; Article; blood analysis; clinical assessment; clinical trial; cohort analysis; controlled study; diabetes mellitus; diagnostic accuracy; diagnostic test accuracy study; diastolic blood pressure; disease registry; dyslipidemia; enzyme linked immunosorbent assay; Europe; female; Fibrosis-4 Index; histology; human; human tissue; hypertension; liver biopsy; liver fibrosis; liver stiffness; major clinical study; male; medical ethics; nonalcoholic fatty liver; Nonalcoholic Fatty Liver Disease Activity Score; nonalcoholic steatohepatitis; platelet count; predictive value; prospective study; screening test; sensitivity and specificity; systolic blood pressure; adolescent; complication; fibrosis; liver cirrhosis; nonalcoholic fatty liver
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-200772 (URN)10.1016/S2468-1253(23)00017-1 (DOI)001164861400001 ()36958367 (PubMedID)2-s2.0-85150789965 (Scopus ID)
Note

Funding: Innovative Medicines Initiative 2 Joint Undertaking

Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2025-02-11
Törnqvist, T., Ekstedt, M., Wiggins, S. & Abrandt Dahlgren, M. (2023). Connecting knowledge: First-year health care students learning in early interprofessional tutorials. Journal of Interprofessional Care, 37(5), 758-766
Open this publication in new window or tab >>Connecting knowledge: First-year health care students learning in early interprofessional tutorials
2023 (English)In: Journal of Interprofessional Care, ISSN 1356-1820, E-ISSN 1469-9567, Vol. 37, no 5, p. 758-766Article in journal (Refereed) Published
Abstract [en]

Collaboration across professional boundaries is an essential aspect of health care, and interprofessional education (IPE) is a common way to help increase students collaborative abilities. Research on how and when IPE should be arranged in a curriculum remains, however, inconclusive. How students actually develop interprofessional competencies have been difficult to demonstrate and is still an under-researched area. Studying IPE in context is therefore important to understand its full complexity. This paper examines how students work with scenarios from professional health care contexts when learning together in interprofessional problem-based learning tutorials during the first year of undergraduate education. The data are video-recorded tutorials of students from medicine, nursing, occupational therapy, speech and language pathology, and physiotherapy programmes. The analysis focuses on students discussing their readings of the literature. Drawing on "Communities of Practice," findings show that students discuss and connect professional knowledge, with "brokers" (the tutors) and "boundary objects" (scenarios) supporting the emergence of students professional knowledge. The scenarios, as boundary objects, also enabled the students to turn into brokers themselves. The paper contributes to research on interprofessional learning and offers support for implementing IPE in the early stages of undergraduate education.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS INC, 2023
Keywords
Boundary objects; brokers; communities of practice; interprofessional education; video-analysis
National Category
Pedagogy
Identifiers
urn:nbn:se:liu:diva-191192 (URN)10.1080/13561820.2022.2162021 (DOI)000906335900001 ()36588170 (PubMedID)
Available from: 2023-01-24 Created: 2023-01-24 Last updated: 2024-08-13Bibliographically approved
Hagström, H. & Ekstedt, M. (2023). Considerations in the search for under-reported alcohol consumption in NAFLD [Letter to the editor]. Journal of Hepatology, 78(2), e66-e67
Open this publication in new window or tab >>Considerations in the search for under-reported alcohol consumption in NAFLD
2023 (English)In: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 78, no 2, p. e66-e67Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2023
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:liu:diva-200821 (URN)10.1016/j.jhep.2022.07.007 (DOI)35863490 (PubMedID)
Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2025-02-11
Edin, C., Ekstedt, M., Scheffel, T., Karlsson, M., Swahn, E., Östgren, C. J., . . . Carlhäll, C.-J. (2022). Ectopic fat is associated with cardiac remodeling - A comprehensive assessment of regional fat depots in type 2 diabetes using multi-parametric MRI.. Frontiers in Cardiovascular Medicine, 9, Article ID 813427.
Open this publication in new window or tab >>Ectopic fat is associated with cardiac remodeling - A comprehensive assessment of regional fat depots in type 2 diabetes using multi-parametric MRI.
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2022 (English)In: Frontiers in Cardiovascular Medicine, E-ISSN 2297-055X, Vol. 9, article id 813427Article in journal (Refereed) Published
Abstract [en]

Background: Different regional depots of fat have distinct metabolic properties and may relate differently to adverse cardiac remodeling. We sought to quantify regional depots of body fat and to investigate their relationship to cardiac structure and function in Type 2 Diabetes (T2D) and controls.

Methods: From the SCAPIS cohort in Linköping, Sweden, we recruited 92 subjects (35% female, mean age 59.5 ± 4.6 years): 46 with T2D and 46 matched controls. In addition to the core SCAPIS data collection, participants underwent a comprehensive magnetic resonance imaging examination at 1.5 T for assessment of left ventricular (LV) structure and function (end-diastolic volume, mass, concentricity, ejection fraction), as well as regional body composition (liver proton density fat fraction, visceral adipose tissue, abdominal subcutaneous adipose tissue, thigh muscle fat infiltration, fat tissue-free thigh muscle volume and epicardial adipose tissue).

Results: Compared to the control group, the T2D group had increased: visceral adipose tissue volume index (P < 0.001), liver fat percentage (P < 0.001), thigh muscle fat infiltration percentage (P = 0.02), LV concentricity (P < 0.001) and LV E/e'-ratio (P < 0.001). In a multiple linear regression analysis, a negative association between liver fat percentage and LV mass (St Beta -0.23, P < 0.05) as well as LV end-diastolic volume (St Beta -0.27, P < 0.05) was found. Epicardial adipose tissue volume and abdominal subcutaneous adipose tissue volume index were the only parameters of fat associated with LV diastolic dysfunction (E/e'-ratio) (St Beta 0.24, P < 0.05; St Beta 0.34, P < 0.01, respectively). In a multivariate logistic regression analysis, only visceral adipose tissue volume index was significantly associated with T2D, with an odds ratio for T2D of 3.01 (95% CI 1.28-7.05, P < 0.05) per L/m2 increase in visceral adipose tissue volume.

Conclusions: Ectopic fat is predominantly associated with cardiac remodeling, independently of type 2 diabetes. Intriguingly, liver fat appears to be related to LV structure independently of VAT, while epicardial fat is linked to impaired LV diastolic function. Visceral fat is associated with T2D independently of liver fat and abdominal subcutaneous adipose tissue.

Place, publisher, year, edition, pages
Frontiers Media SA, 2022
Keywords
cardiac remodeling, ectopic fat, left ventricular diastolic function, left ventricular structure, magnetic resonance imaging, type 2 diabetes, visceral fat
National Category
Endocrinology and Diabetes Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:liu:diva-190027 (URN)10.3389/fcvm.2022.813427 (DOI)000890713700001 ()35966535 (PubMedID)
Note

This work was funded by the Swedish Research Council, theSwedish Heart and Lung Foundation, and through ALF GrantsRegion Östergötland.

Available from: 2022-11-17 Created: 2022-11-17 Last updated: 2023-05-04
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