↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Träfflista för sökning "WFRF:(Ekstedt Mattias) "

Sökning: WFRF:(Ekstedt Mattias)

Resultat 1-50 av 128

Sortera/gruppera träfflistan

Sortering: Träffar per sida:

Numrering	Referens	Omslagsbild	Hitta
1.	Aberg, Fredrik, et al. (författare) A Dynamic Aspartate-to-Alanine Aminotransferase Ratio Provides Valid Predictions of Incident Severe Liver Disease 2021 Ingår i: HEPATOLOGY COMMUNICATIONS. - : John Wiley & Sons. - 2471-254X. ; 5:6, s. 1021-1035 Tidskriftsartikel (refereegranskat)abstract The aspartate-to-alanine aminotransferase ratio (AAR) is associated with liver fibrosis, but its predictive performance is suboptimal. We hypothesized that the association between AAR and liver disease depends on absolute transaminase levels and developed and validated a model to predict liver-related outcomes in the general population. A Cox regression model based on age, AAR, and alanine aminotransferase (ALT) level (dynamic AAR [dAAR]) using restricted cubic splines was developed in Finnish population-based health-examination surveys (FINRISK, 2002-2012; n = 18,067) with linked registry data for incident liver-related hospitalizations, hepatocellular carcinoma, or liver death. The model was externally validated for liver-related outcomes in a Swedish population cohort (Swedish Apolipoprotein Mortality Risk [AMORIS] subcohort; n = 126,941) and for predicting outcomes and/or prevalent fibrosis/cirrhosis in biopsied patients with nonalcoholic fatty liver disease (NAFLD), chronic hepatitis C, or alcohol-related liver disease (ALD). The dynamic AAR model predicted liver-related outcomes both overall (optimism-corrected C-statistic, 0.81) and in subgroup analyses of the FINRISK cohort and identified persons with >10% risk for liver-related outcomes within 10 years. In independent cohorts, the C-statistic for predicting liver-related outcomes up to a 10-year follow-up was 0.72 in the AMORIS cohort, 0.81 in NAFLD, and 0.75 in ALD. Area-under-the-curve (AUC) for detecting prevalent cirrhosis was 0.80-0.83 in NAFLD, 0.80 in hepatitis C, but only 0.71 in ALD. In ALD, model performance improved when using aspartate aminotransferase instead of ALT in the model (C-statistic, 0.84 for outcome; AUC, 0.82 for prevalent cirrhosis). Conclusion: A dAAR score provides prospective predictions for the risk of incident severe liver outcomes in the general population and helps detect advanced liver fibrosis/cirrhosis. The dAAR score could potentially be used for screening the unselected general population and as a trigger for further liver evaluations.
2.	Akbari, Camilla, et al. (författare) Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD 2024 Ingår i: JHEP Reports. - : Elsevier. - 2589-5559. ; 6:2 Tidskriftsartikel (refereegranskat)abstract Background & AimsLong-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.MethodsWe 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.ResultsMALO 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).ConclusionsThis 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 implicationsSeveral 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.
3.	Alfredsson, Joakim, 1962-, et al. (författare) Bleeding complications with clopidogrel or ticagrelor in ST-elevation myocardial infarction patients : A real life cohort study of two treatment strategies 2020 Ingår i: IJC Heart & Vasculature. - : Elsevier. - 2352-9067. ; 27 Tidskriftsartikel (refereegranskat)abstract IntroductionDual antiplatelet therapy (DAPT), including potent P2Y12 inhibition after ST-elevation myocardial infarction (STEMI) is recommended in clinical guidelines. However, bleeding complications are common, and associated with worse outcomes. The aim of this study was to assess incidence of bleeding events with a clopidogrel-based compared to a ticagrelor-based DAPT strategy, in a real world population. Secondary aims were to assess ischemic complications and mortality.Methods and ResultsWe identified 330 consecutive STEMI patients with a clopidogrel-based and 330 with a ticagrelor-based DAPT strategy. Patientś medical records were searched for bleeding and ischemic complications, over 6 months follow-up.The two groups were well balanced in baseline characteristics, age (69 years inboth groups), sex (31% vs 32% females), history of diabetes (19% vs 21%), hypertension (43% in both) and MI (17% vs 15%). There was no difference in CRUSADE bleeding score (28 vs 29). After discharge, there were more than twice as many bleeding events with a ticagrelor-based compared with a clopidogrel-based strategy (13.3% vs. 6.5%, p = 0.005). Bleeding events included significantly more severe bleeding complications (TIMI major/minor [5.8 vs 1.0, p = 0.001]) during the ticagrelor-based period. There was no significant difference in the composite of death, MI or stroke (7.8% vs 7.1%, p = 0.76).ConclusionsIn this observational study, a ticagrelor-based DAPT strategy was associated with significantly more bleeding complications, without any significant change in death, MI or stroke. Larger studies are needed to determine whether bleeding complications off-sets benefits with a more potent DAPT strategy in older and more comorbid real-life patients.
4.	Anstee, Quentin M., et al. (författare) Correction: Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort (vol 12, pg 505, 2020) 2021 Ingår i: Journal of Hepatology. - : ELSEVIER. - 0168-8278 .- 1600-0641. ; 74:5, s. 1274-1275 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
5.	Anstee, Quentin M., et al. (författare) Correction: Genome-wide association study of non- alcoholic fatty liver and steatohepatitis in a histologically characterised cohort ( vol 73, pp 505-515 , 2020 ) 2023 Ingår i: Journal of Hepatology. - : ELSEVIER. - 0168-8278 .- 1600-0641. ; 78:5, s. 1085-1086 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
6.	Anstee, Quentin M., et al. (författare) Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically-characterised cohort 2020 Ingår i: Journal of Hepatology. - : Elsevier. - 0168-8278 .- 1600-0641. ; 73:3, s. 505-515 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND AIMS: Genetic factors associated with non-alcoholic fatty liver disease (NAFLD) remain incompletely understood. To date, most GWAS studies have adopted radiologically assessed hepatic triglyceride content as reference phenotype and so cannot address steatohepatitis or fibrosis. We describe a genome-wide association study (GWAS) encompassing the full spectrum of histologically characterized NAFLD.METHODS: The GWAS involved 1483 European NAFLD cases and 17781 genetically-matched population controls. A replication cohort of 559 NAFLD cases and 945 controls was genotyped to confirm signals showing genome-wide or close to genome-wide significance.RESULTS: Case-control analysis identified signals showing p-values ≤ 5 x 10-8 at four locations (chromosome (chr) 2 GCKR/C2ORF16; chr4 HSD17B13; chr19 TM6SF2; chr22 PNPLA3) together with two other signals with p<1 x10-7 (chr1 near LEPR and chr8 near IDO2/TC1). Case-only analysis of quantitative traits steatosis, disease activity score, NAS and fibrosis showed that the PNPLA3 signal (rs738409) was genome-wide significantly associated with steatosis, fibrosis and NAS score and identified a new signal (PYGO1 rs62021874) with close to genome-wide significance for steatosis (p=8.2 x 10-8). Subgroup case-control analysis for NASH confirmed the PNPLA3 signal. The chr1 LEPR SNP also showed genome-wide significance for this phenotype. Considering the subgroup with advanced fibrosis (≥F3), the signals on chromosomes 2, 19 and 22 remained genome-wide significant. With the exception of GCKR/C2ORF16, the genome-wide significant signals replicated.CONCLUSIONS: This study confirms PNPLA3 as a risk factor for the full histological spectrum of NAFLD at genome-wide significance levels, with important contributions from TM6SF2 and HSD17B13. PYGO1 is a novel steatosis modifier, suggesting relevance of Wnt signalling pathways in NAFLD pathogenesis.
7.	Balkhed, Wile, et al. (författare) Repeated measurements of non-invasive fibrosis tests to monitor the progression of non-alcoholic fatty liver disease : A long-term follow-up study 2022 Ingår i: Liver international (Print). - Chichester, United Kingdom : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 42:7, s. 1546-1556 Tidskriftsartikel (refereegranskat)abstract Background and Aims: The presence of advanced hepatic fibrosis is the prime marker for the prediction of liver-related complications in non-alcoholic fatty liver disease (NAFLD). Blood-based non-invasive tests (NITs) have been developed to evaluate fibrosis and identify patients at risk. Current guidelines propose monitoring the progression of NAFLD using repeated NITs at 2-3-year intervals. The aim of this study was to evaluate the association of changes in NITs measured at two time points with the progression of NAFLD.Methods. We retrospectively included NAFLD patients with NIT measurements in whom the baseline hepatic fibrosis stage had been assessed by biopsy or transient elastography (TE). Subjects underwent follow-up visits at least 1 year from baseline to evaluate the progression of NAFLD. NAFLD progression was defined as the development of end-stage liver disease or fibrosis progression according to repeat biopsy or TE. The following NITs were calculated at baseline and follow-up: Fibrosis-4 (FIB-4), NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet ratio index (APRI) and dynamic aspartate-to-alanine aminotransferase ratio (dAAR).Results: One hundred and thirty-five patients were included with a mean follow-up of 12.6 +/- 8.5 years. During follow-up, 41 patients (30%) were diagnosed with progressive NAFLD. Change in NIT scores during follow-up was significantly associated with disease progression for all NITs tested except for NFS. However, the diagnostic precision was suboptimal with area under the receiver operating characteristics 0.56-0.64 and positive predictive values of 0.28-0.36 at sensitivity fixed at 90%.Conclusions: Change of FIB-4, NFS, APRI, and dAAR scores is only weakly associated with disease progression in NAFLD. Our findings do not support repeated measurements of these NITs for monitoring the course of NAFLD.
8.	Bergram, Martin, et al. (författare) Low awareness of non-alcoholic fatty liver disease in patients with type 2 diabetes in Swedish Primary Health Care 2022 Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis Ltd. - 0036-5521 .- 1502-7708. ; 57:1, s. 60-69 Tidskriftsartikel (refereegranskat)abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is more common in patients with type 2 diabetes mellitus (T2DM) compared to individuals without. Recent guidelines recommend screening for NAFLD in patients with T2DM. Our aim was to investigate the prevalence of NAFLD in patients with T2DM in a Swedish primary health care setting, how they are cared for and assess the risk of biochemical signs of advanced fibrosis. Material and methods In this cohort study, patients with T2DM from five primary health care centers were included. Medical records were retrospectively reviewed and living habits, medical history, results of diagnostic imaging and anthropometric and biochemical features were noted in a standardized form. The risk of steatosis and advanced fibrosis was assessed using commonly used algorithms (FLI, HSI, NAFLD-LFS, NAFLD ridge score, FIB-4 and NFS). Results In total 350 patients were included. Diagnostic imaging had been performed in 132 patients and of these, 34 (26%) had steatosis, which was not noted in the medical records in 16 (47%) patients. One patient with steatosis had been referred to a hepatologist. Of assessable patients, 71-97% had a high to intermediate risk of steatosis and 29-65% had an intermediate to high risk of advanced fibrosis according to the algorithms used. Conclusion This study indicates a high prevalence of NAFLD among T2DM patients in Swedish primary care. Patients with known NAFLD were followed up to a very low extent. Using fibrosis algorithms in primary health care would result in many patients needing further assessment in secondary care.
9.	Blomdahl, Julia, et al. (författare) Moderate alcohol consumption is associated with advanced fibrosis in non-alcoholic fatty liver disease and shows a synergistic effect with type 2 diabetes mellitus 2021 Ingår i: Metabolism. - : Elsevier. - 0026-0495 .- 1532-8600. ; 115 Tidskriftsartikel (refereegranskat)abstract Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Whether moderate alcohol consumption plays a role for progression of NAFLD is disputed. Moreover, it is not known which tool is ideal for assessment of alcohol consumption in NAFLD. This study aimed to evaluate if moderate alcohol consumption assessed with different methods, including the biological marker phosphatidylethanol (PEth), is associated with advanced fibrosis in NAFLD. Methods: We conducted a cross-sectional study of patients with biopsy-proven NAFLD. All participants were clinically evaluated with medical history, blood tests, and anthropometric measurements. Alcohol consumption was assessed using PEth in blood, the questionnaire AUDIT-C, and clinical interview. Findings: 86 patients were included of which 17% had advanced fibrosis. All participants reported alcohol consumption < 140 g/week. Average weekly alcohol consumption was higher in the group with advanced fibrosis. Moderate alcohol consumption, independently of the method of assessment, was associated with increased probability of advanced fibrosis (adjusted OR 5.5-9.7, 95% CI 1.05-69.6). Patients with type 2 diabetes mellitus (T2DM) consuming moderate amounts of alcohol had a significantly higher rate of advanced fibrosis compared with those consuming low amounts (50.0-60.0% vs. 33-21.6%, p < 0.05). Conclusions: Moderate alcohol consumption, irrespective of assessment method (clinical interview, AUDIT-C, and PEth), was associated with advanced fibrosis. PEth in blood >= 50 ng/mL may be a biological marker indicating increased risk for advanced fibrosis in NAFLD. Patients with T2DM consuming moderate amounts of alcohol had the highest risk of advanced fibrosis, indicating a synergistic effect of insulin resistance and alcohol on the histopathological progression of NAFLD. (C) 2020 The Author(s). Published by Elsevier Inc.
10.	Blomdahl, Julia, et al. (författare) Moderate alcohol consumption is associated with significant fibrosis progression in NAFLD 2023 Ingår i: HEPATOLOGY COMMUNICATIONS. - : LIPPINCOTT WILLIAMS & WILKINS. - 2471-254X. ; 7:1 Tidskriftsartikel (refereegranskat)abstract The effect of moderate alcohol consumption on NAFLD histology is disputed. Assessment of alcohol consumption is commonly performed with interview or questionnaires. Phosphatidylethanol (PEth) in blood is a highly sensitive and specific alcohol biomarker, which only forms in the presence of ethanol. PEth has hitherto not been evaluated in longitudinal NAFLD studies. This study aimed to examine the impact of moderate alcohol consumption on histologic progression and evaluate the utility of PEth in NAFLD. NAFLD patients with serial biopsies were reviewed for inclusion in the study. At baseline, all patients reported alcohol consumption <140 g/week. Anthropometric and biochemical measurements were performed at baseline and follow-up. Alcohol consumption was assessed thoroughly at follow-up with clinical interview, the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) questionnaire, and analysis of PEth in whole blood. Eighty-two patients were included. Mean follow-up time was 17.2 years (SD & PLUSMN;6.0). Patients with significant fibrosis progression (defined as progression of & GE;2 stages or development of cirrhosis-related complications) reported higher alcohol consumption and had significantly higher PEth. Consumption >66-96 g/week (but <140 g) (i.e. moderate alcohol consumption) was associated with increased risk of significant fibrosis progression compared with no or low consumption. PEth & GE;48 ng/mL and binge drinking showed the highest risk for significant fibrosis progression (aOR: 5.9; 95% CI: 1.6-21.4) and aOR: 5.1; 95% CI: 1.4-18.1, respectively). NAFLD patients consuming moderate amounts of alcohol are at increased risk for significant fibrosis progression and development of cirrhosis-related complications. PEth is a potential biomarker to assess harmful alcohol consumption in NAFLD. Patients reporting moderate consumption or exhibiting PEth & GE;48 ng/mL should be advised to reduce alcohol consumption.
11.	Blomdahl, Julia, 1991- (författare) Non-Alcoholic Fatty Liver Disease : Insights into Alcohol Consumption, Genetics, and Proteomics 2023 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract NAFLD (Non-Alcoholic Fatty Liver Disease) affects approximately a quarter of the global population and is closely linked to type 2 diabetes mellitus and obesity. The disease spectrum ranges from steatosis and steatohepatitis to fibrosis, cirrhosis, and hepatocellular cancer. However, accurately predicting which patients will experience a progressive disease course remains a significant challenge. The variant gene of PNPLA3 is known to be associated with NAFLD and a more progressive disease, although its precise function remains unclear. Patients with NAFLD typically consume small to moderate amounts of alcohol, with recommended thresholds set at a maximum of 210 gram per week for males and 140 grams per week in females. However, the impact of alcohol consumption on liver disease in NAFLD remains disputed, with conflicting research findings. Liver biopsy is considered the gold standard for diagnosing NAFLD. However, due to its impracticality for such a large population with the condition, various non-invasive methods have been explored for diagnosing and evaluating NAFLD. This thesis aimed to investigate the potential effects of moderate alcohol consumption on NAFLD histology, explore the potential role of variant PNPLA3 in NAFLD, and assess the use of proteomics in classifying fibrosis. In Papers I and II, moderate alcohol consumption was assessed through questionnaires, clinical interviews, and measurement of the direct alcohol biomarker phosphatidylethanol (PEth). Paper I, a cross-sectional study including 86 participants, showed an association between moderate consumption and advanced fibrosis. Moderate consumption was defined as consuming more than 66 grams of ethanol per week or a PEth-value over 50 ng/mL. Notably, individuals with both moderate alcohol consumption and a diagnosis of type 2 diabetes exhibited significantly more advanced fibrosis. Paper II was a cohort study where 82 participants were followed over 17.2 years. Similarly, participants with moderate alcohol consumption displayed significant fibrosis progression. The strongest association was observed in participants with PEth-value of 48 ng/mL or higher, or those with binge drinking. In Paper III, the potential role of variant PNPLA3 was explored, exhibiting impaired autophagic flux and reduced lipophagy in variant PNPLA3 cells. Liver biopsies of NAFLD individuals with variant PNPLA3 displayed an accumulation of lipid droplets positive for both PNPLA3 and LC3 (a common marker of the autophagosome). This suggests that PNPLA3 is part of the lipophagy process, which is impaired in the variant gene and contributes to steatosis. Paper IV examined two independent NAFLD cohorts. In the discovery cohort, 60 participants with biopsy-proven NAFLD were included, while 59 participants were included in the validation cohort. The study evaluated 266 proteins and found that a biomarker model combining ACE2, HGF, and IGFBP-7 distinguished between different fibrosis stages (F0–1 and F2–4) in both cohorts. In summary, measuring phosphatidylethanol is advisable in NAFLD patient evaluations. Elevated PEth-levels (≥48 ng/mL) or alcohol consumption exceeding 66 grams per week should warrant advice to abstain from alcohol. PNPLA3 is implicated in NAFLD pathophysiology, potentially through impaired lipophagy. While its clinical application remains uncertain, genetic profiling for NAFLD risk assessment may become part of future non-invasive approaches. Additionally, proteomics holds promise for non-invasive NAFLD assessment, with the combination of ACE2, HGF, and IGFBP-7 identifying significant fibrosis in two separate cohorts.
12.	Boström, E A, et al. (författare) Resistin is Associated with Breach of Tolerance and Anti-nuclear Antibodies in Patients with Hepatobiliary Inflammation 2011 Ingår i: Scandinavian Journal of Immunology. - : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 463-470 Tidskriftsartikel (refereegranskat)abstract Resistin is a cysteine-rich protein, which is abundantly expressed at the site of inflammation, and acts as a regulator of the NF-kB-dependent cytokine cascade. The aim of this study was to evaluate resistin levels in relation to inflammatory mediators, disease phenotype and autoantibody status in a spectrum of pathological conditions of the gastrointestinal tract. Resistin levels were measured with an ELISA in sera originated from 227 patients and 40 healthy controls (HC). Fifty patients diagnosed with non-alcoholic fatty liver disease (NAFLD), 53 ulcerative colitis (UC), 51 Crohns disease (CD), 46 autoimmune hepatitis (AIH) and 27 primary sclerosing cholangitis (PSC) were included. The sera were analysed with respect to biochemical parameters of systemic inflammation and liver function and to the presence of antibodies to nuclear antigens (ANA), mitochondria (AMA) and smooth muscle (SMA). Compared with HC, resistin levels were raised in AIH (P = 0.017) and PSC (P = 0.03); compared with NAFLD, levels were elevated in CD (P = 0.041), AIH (P andlt; 0.001) and PSC (P andlt; 0.001). Patients with elevated levels of resistin were more often treated with corticosteroids, but no difference was found between active disease and clinical remission. Resistin levels were significantly higher in ANA-positive individuals compared with ANA-negative (P = 0.025). Resistin levels were directly correlated with IL-6 (r = 0.30, P = 0.02) and IL-8 (r = 0.51, P andlt; 0.001). Elevated levels of resistin were prominent in patients with hepatobiliary inflammation and were associated with breach of self-tolerance, i.e. ANA positivity. Thus, we propose that resistin may be an important marker of disease severity in autoantibody-mediated gastrointestinal inflammatory diseases.
13.	Boursier, Jerome, et al. (författare) Non-invasive tests accurately stratify patients with NAFLD based on their risk of liver-related events 2022 Ingår i: Journal of Hepatology. - : ELSEVIER. - 0168-8278 .- 1600-0641. ; 76:5, s. 1013-1020 Tidskriftsartikel (refereegranskat)abstract Background & Aims: Previous studies on the prognostic significance of non-invasive liver fibrosis tests in non-alcoholic fatty liver disease (NAFLD) lack direct comparison to liver biopsy. We aimed to evaluate the prognostic accuracy of fibrosis-4 (FIB4) and vibration-controlled transient elastography (VCTE), compared to liver biopsy, for the prediction of liver-related events (LREs) in NAFLD. Methods: A total of 1,057 patients with NAFLD and baseline FIB4 and VCTE were included in a multicenter cohort. Of these patients, 594 also had a baseline liver biopsy. The main study outcome during follow-up was occurrence of LREs, a composite endpoint combining cirrhosis complications and/or hepatocellular carcinoma. Discriminative ability was evaluated using Harrells C-index. Results: FIB4 and VCTE showed good accuracy for the prediction of LREs, with Harrells C-indexes >0.80 (0.817 [0.768-0.866] vs. 0.878 [0.835-0.921], respectively, p = 0.059). In the biopsy subgroup, Harrells C-indexes of histological fibrosis staging and VCTE were not significantly different (0.932 [0.910-0.955] vs. 0.881 [0.832-0.931], respectively, p = 0.164), while both significantly outperformed FIB4 for the prediction of LREs. FIB4 and VCTE were independent predictors of LREs in the whole study cohort. The stepwise FIB4-VCTE algorithm accurately stratified the risk of LREs: compared to patients with "FIB4 <1.30", those with "FIB4 >- 1.30 then VCTE <8.0 kPa" had similar risk of LREs (adjusted hazard ratio [aHR] 1.3; 95% CI 0.3-6.8), whereas the risk of LREs significantly increased in patients with "FIB4 >1.30 then VCTE 8.0-12.0 kPa" (aHR 3.8; 95% CI 1.3-10.9), and even more for those with "FIB4 >-1.30 then VCTE >12.0 kPa" (aHR 12.4; 95% CI 5.1- 30.2). Conclusion: VCTE and FIB4 accurately stratify patients with NAFLD based on their risk of LREs. These non-invasive tests are alternatives to liver biopsy for the identification of patients in need of specialized management. Lay summary: The amount of fibrosis in the liver is closely associated with the risk of liver-related complications in nonalcoholic fatty liver disease (NAFLD). Liver biopsy currently remains the reference standard for the evaluation of fibrosis, but its application is limited by its invasiveness. Therefore, we evaluated the ability of non-invasive liver fibrosis tests to predict liver-related complications in NAFLD. Our results show that the blood test FIB4 and transient elastography stratify the risk of liver-related complications in NAFLD, and that transient elastography has similar prognostic accuracy as liver biopsy. These results support the use of non-invasive liver fibrosis tests instead of liver biopsy for the management of patients with NAFLD.(C) 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
14.	Buzzetti, Elena, et al. (författare) Collagen proportionate area is an independent predictor of long-term outcome in patients with non-alcoholic fatty liver disease 2019 Ingår i: Alimentary Pharmacology and Therapeutics. - : WILEY. - 0269-2813 .- 1365-2036. ; 49:9, s. 1214-1222 Tidskriftsartikel (refereegranskat)abstract Background Collagen proportionate area (CPA) measurement is a technique that quantifies fibrous tissue in liver biopsies by measuring the amount of collagen deposition as a proportion of the total biopsy area. CPA predicts clinical outcomes in patients with HCV and can sub-classify cirrhosis. Aim To test the ability of CPA to quantify fibrosis and predict clinical outcomes in patients with NAFLD. Methods We assessed consecutive patients with biopsy-proven NAFLD from three European centres. Clinical and laboratory data were collected at baseline and at the time of the last clinical follow-up or death. CPA was performed at two different objective magnifications, whole biopsy macro and x4 objective magnification, named standard (SM) and high (HM) magnification respectively. The correlation between CPA and liver stiffness was assessed in a sub-group of patients. Results Of 437 patients, 32 (7.3%) decompensated and/or died from liver-related causes during a median follow-up of 103 months. CPA correlated with liver stiffness and liver fibrosis stage across the whole spectrum of fibrosis. HM CPA was significantly higher than SM CPA in stages F0-F3 but similar in cirrhosis, reflecting a higher ability to capture pericellular/perisinusoidal fibrosis at early stages. Age at baseline (HR: 1.04, 95% CI: 1.01-1.08), HM CPA (HR: 1.04 per 1% increase, 95% CI: 1.01-1.08) and presence of advanced fibrosis (HR: 15.4, 95% CI: 5.02-47.84) were independent predictors of liver-related clinical outcomes at standard and competing risk multivariate Cox-regression analysis. Conclusions CPA accurately measures fibrosis and is an independent predictor of clinical outcomes in NAFLD; hence it merits further evaluation as a surrogate endpoint in clinical trials.
15.	Byenfeldt, Marie, et al. (författare) Altered probe pressure and body position increase diagnostic accuracy for men and women in detecting hepatic steatosis using quantitative ultrasound 2024 Ingår i: European Radiology. - : SPRINGER. - 0938-7994 .- 1432-1084. Tidskriftsartikel (refereegranskat)abstract ObjectivesTo evaluate the diagnostic performance of ultrasound guided attenuation parameter (UGAP) for evaluating liver fat content with different probe forces and body positions, in relation to sex, and compared with proton density fat fraction (PDFF).MethodsWe prospectively enrolled a metabolic dysfunction-associated steatotic liver disease (MASLD) cohort that underwent UGAP and PDFF in the autumn of 2022. Mean UGAP values were obtained in supine and 30 degrees left decubitus body position with normal 4 N and increased 30 N probe force. The diagnostic performance was evaluated by the area under the receiver operating characteristic curve (AUC).ResultsAmong 60 individuals (mean age 52.9 years, SD 12.9; 30 men), we found the best diagnostic performance with increased probe force in 30 degrees left decubitus position (AUC 0.90; 95% CI 0.82-0.98) with a cut-off of 0.58 dB/cm/MHz. For men, the best performance was in supine (AUC 0.91; 95% CI 0.81-1.00) with a cut-off of 0.60 dB/cm/MHz, and for women, 30 degrees left decubitus position (AUC 0.93; 95% CI 0.83-1.00), with a cut-off 0.56 dB/cm/MHz, and increased 30 N probe force for both genders. No difference was in the mean UGAP value when altering body position. UGAP showed good to excellent intra-reproducibility (Intra-class correlation 0.872; 95% CI 0.794-0.921).ConclusionUGAP provides excellent diagnostic performance to detect liver fat content in metabolic dysfunction-associated steatotic liver diseases, with good to excellent intra-reproducibility. Regardless of sex, the highest diagnostic accuracy is achieved with increased probe force with men in supine and women in 30 degrees left decubitus position, yielding different cut-offs.Clinical relevance statementThe ultrasound method ultrasound-guided attenuation parameter shows excellent diagnostic accuracy and performs with good to excellent reproducibility. There is a possibility to alter body position and increase probe pressure, and different performances for men and women should be considered for the highest accuracy.Key Points center dot There is a possibility to alter body position when performing the ultrasound method ultrasound-guided attenuation parameter.center dot Increase probe pressure for the highest accuracy.center dot Different performances for men and women should be considered.Key Points center dot There is a possibility to alter body position when performing the ultrasound method ultrasound-guided attenuation parameter.center dot Increase probe pressure for the highest accuracy.center dot Different performances for men and women should be considered.Key Points center dot There is a possibility to alter body position when performing the ultrasound method ultrasound-guided attenuation parameter.center dot Increase probe pressure for the highest accuracy.center dot Different performances for men and women should be considered.
16.	Dulai, Parambir S, et al. (författare) Increased risk of mortality by fibrosis stage in non-alcoholic fatty liver disease : Systematic Review and Meta-analysis. 2017 Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 65:5, s. 1557-1565 Forskningsöversikt (refereegranskat)abstract BACKGROUND: Liver fibrosis is the most important predictor of mortality in nonalcoholic fatty liver disease (NAFLD). Quantitative risk of mortality by fibrosis stage has not been systematically evaluated. We aimed to quantify the fibrosis stage-specific risk of all-cause and liver-related mortality in NAFLD.METHODS: Through a systematic review and meta-analysis, we identified 5 adult NAFLD cohort studies reporting fibrosis stage specific mortality (0-4). Using fibrosis stage 0 as a reference population, fibrosis stage-specific mortality rate ratios (MRR) with 95% confidence intervals (CI), for all-cause and liver-related mortality, were estimated. The study is reported according to the PRISMA statement.RESULTS: 1,495 NAFLD patients with 17,452 patient years of follow-up were included. Compared to NAFLD patients with no fibrosis (stage 0), NAFLD patients with fibrosis were at an increased risk for all-cause mortality and this risk increased with increase in the stage of fibrosis: stage 1, MRR, 1.58 (95% CI 1.19-2.11); stage 2, MRR, 2.52 (95% CI 1.85-3.42); stage 3, MRR, 3.48 (95% CI 2.51-4.83), and stage 4, MRR, 6.40 (95% CI 4.11-9.95). The results were more pronounced as the risk of liver-related mortality increased exponentially with increase in the stage of fibrosis: stage 1, MRR, 1.41 (95% CI 0.17-11.95); stage 2, MRR, 9.57 (95% CI 1.67-54.93); stage 3, MRR, 16.69 (95% CI 2.92-95.36); and stage 4, MRR, 42.30 (95% CI 3.51-510.34).LIMITATIONS: Inability to adjust for co-morbid conditions or demographics known to impact fibrosis progression in NAFLD, and the inclusion of patients with simple steatosis and NASH without fibrosis in the reference comparison group.CONCLUSION: The risk of liver-related mortality increases exponentially with increase in fibrosis stage. These data have important implications in assessing utility of each stage and benefits of regression of fibrosis from one stage to another. This article is protected by copyright. All rights reserved.
17.	Edin, Carl, et al. (författare) Ectopic fat is associated with cardiac remodeling - A comprehensive assessment of regional fat depots in type 2 diabetes using multi-parametric MRI. 2022 Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; 9 Tidskriftsartikel (refereegranskat)abstract 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.
18.	Edin, Carl, et al. (författare) Liver fibrosis is associated with left ventricular remodeling : insight into the liver-heart axis 2024 Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. Tidskriftsartikel (refereegranskat)abstract 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.
19.	Ekstedt, Mattias, et al. (författare) Alcohol consumption is associated with progression of hepatic fibrosis in non-alcoholic fatty liver disease 2009 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 44:3, s. 366-374 Tidskriftsartikel (refereegranskat)abstract Objective: Moderate alcohol consumption has been reported to be inversely associated with cardiovascular disease and total mortality. The importance of non-alcoholic fatty liver disease (NAFLD) is increasing and many NAFLD patients suffer from cardiovascular disease. In these patients, moderate alcohol consumption could be beneficial. The aim of this study was to investigate whether low alcohol intake, consistent with the diagnosis of NAFLD, is associated with fibrosis progression in established NAFLD. Material and methods: Seventy-one patients originally referred because of chronically elevated liver enzymes and diagnosed with biopsy-proven NAFLD were re-evaluated. A validated questionnaire combined with an oral interview was used to assess weekly alcohol consumption and the frequency of episodic drinking. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of endstage liver disease during follow-up. Results: Mean follow-up (SD) was 13.8 (1.2) years between liver biopsies. At follow-up, 17 patients (24%) fulfilled the criteria for significant fibrosis progression. The proportion of patients reporting heavy episodic drinking at least once a month was higher among those with significant fibrosis progression (p=0.003) and a trend towards higher weekly alcohol consumption was also seen (p=0.061). In a multivariate binary logistic regression analysis, heavy episodic drinking (p0.001) and insulin resistance (p0.01) were independently associated with significant fibrosis progression. Conclusions: Moderate alcohol consumption, consistent with the diagnosis of NAFLD to be set, is associated with fibrosis progression in NAFLD. These patients should be advised to refrain from heavy episodic drinking.
20.	Ekstedt, Mattias, et al. (författare) Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up 2015 Ingår i: Hepatology. - : John Wiley & Sons. - 0270-9139 .- 1527-3350. ; 61:5, s. 1547-1554 Tidskriftsartikel (refereegranskat)abstract 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.
21.	Ekstedt, Mattias, et al. (författare) Long-term follow-up of patients with NAFLD and elevated liver enzymes. 2006 Ingår i: Hepatology. - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 44:4, s. 865-873 Tidskriftsartikel (refereegranskat)abstract Nonalcoholic fatty liver disease (NAFLD) is the most common cause of elevated liver enzymes in patients of developed countries. We determined the long-term clinical and histological courses of such patients. In a cohort study, 129 consecutively enrolled patients diagnosed with biopsy-proven NAFLD were reevaluated. Survival and causes of death were compared with a matched reference population. Living NAFLD patients were offered repeat liver biopsy and clinical and biochemical investigation. Mean follow-up (SD) was 13.7 (1.3) years. Mortality was not increased in patients with steatosis. Survival of patients with nonalcoholic steatohepatitis (NASH) was reduced (P = .01). These subjects more often died from cardiovascular (P = .04) and liver-related (P = .04) causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. The absence of periportal fibrosis at baseline had a negative predictive value of 100% in predicting liver-related complications. At follow-up, 69 of 88 patients had diabetes or impaired glucose tolerance. Progression of liver fibrosis occurred in 41%. These subjects more often had a weight gain exceeding 5 kg (P = .02), they were more insulin resistant (P = .04), and they exhibited more pronounced hepatic fatty infiltration (P = .03) at follow-up. In conclusion, NAFLD with elevated liver enzymes is associated with a clinically significant risk of developing end-stage liver disease. Survival is lower in patients with NASH. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.
22.	Ekstedt, Mattias, et al. (författare) Low clinical relevance of the nonalcoholic fatty liver disease activity score (NAS) in predicting fibrosis progression 2012 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa Healthcare. - 0036-5521 .- 1502-7708. ; 47:1, s. 108-115 Tidskriftsartikel (refereegranskat)abstract Background/Aims. The nonalcoholic fatty liver disease (NAFLD) activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD. Methods. One hundred and twenty-nine patients with biopsy-proven NAFLD were included in a long-term histological follow-up study. Clinical course and change in fibrosis stage were compared between nonalcoholic steatohepatitis (NASH), “borderline NASH,” and “not NASH” patients. Significant fibrosis progression was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up. Results. Eighty-eight patients accepted reevaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3–16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend toward higher baseline NAS was seen in patients (n = 7) who developed end-stage liver disease (3.1 ± 0.9 vs. 2.2 ± 1.0; p = 0.050). Baseline NAS was associated with progressive disease in a univariate binary logistic regression analysis (p = 0.024), but no difference was seen in the multivariate analysis including the NAS, portal inflammation, and perisinusoidal fibrosis. Moreover, 18% of patients without NASH progressed significantly in fibrosis stage. Conclusions. The ability of the NAS to predict progression of NAFLD is poor. The clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS score groups. To use the NAS as endpoint in treatment trial is not justified.
23.	Ekstedt, Mattias, 1976- (författare) Non-Alcoholic Fatty Liver Disease : A clinical and histopathological study 2008 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Fatty liver has previously often been associated with excessive alcohol consumption. During the last two decades, the interest in fatty liver occurring in non-drinkers i.e. non-alcoholic fatty liver disease (NAFLD) has increased dramatically. Today, NAFLD is considered as the most common liver disease in the developed world. It is strongly associated with obesity, insulin resistance, and hypertension. Thus, NAFLD is considered as the hepatic manifestation of the metabolic syndrome.The spectrum of NAFLD includes: simple fatty liver without necroinflammatory activity; non-alcoholic steatohepatitis (NASH), a condition characterised by hepatocellular injury, inflammation, and fibrosis; cirrhosis; and in some individuals hepatocellular carcinoma.The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the pathologist uses a four-graded scale: 0–3 or none, slight, moderate and severe. In this thesis we show that there is a considerable inter- and intraindividual variation in such scoring methods and that a more standardised and quantitative approach is preferable. The area/volume of fat in liver biopsies is greatly overestimated when assessed semiquantitatively. Moreover, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis.The long-term clinical and histopathological course of 129 consecutively enrolled NAFLD patients was studied. Mean follow-up (SD) was 13.7 (1.3) years. Survival of NASH patients was reduced compared with a matched reference population. These subjects more often died from cardiovascular and liver-related causes. Seven patients (5.4%) developed end-stage liver disease, including 3 patients with hepatocellular carcinoma. Most NAFLD patients will develop diabetes or impaired glucose tolerance in the long term. Progression of liver fibrosis is associated with more pronounced insulin resistance and significant weight gain.During follow-up, 17 patients had been prescribed a statin. At follow-up, patients on medication with statins had significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Although patients under statin treatment exhibited a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage. It is concluded that statins can be prescribed safely in patients with elevated liver enzymes because of NAFLD.Alcohol consumption was evaluated with a validated questionnaire combined with an oral interview. In a multivariate analysis moderate alcohol consumption, particularly when frequency of heavy episodic drinking was analysed, consistent with the diagnosis of NAFLD to be set, was independently associated with fibrosis progression in NAFLD.The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. We evaluated the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in our cohort of NAFLD patients. Although the NAS was independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score was limited due to significant overlap in clinical development between NAS-score groups.
24.	Ekstedt, Mattias, et al. (författare) Nonalcoholic Fatty Liver Disease Activity Score and Mortality: Imperfect But Not Insignificant REPLY 2016 Ingår i: Hepatology. - : Wiley-Blackwell. - 0270-9139 .- 1527-3350. ; 64:1, s. 310-311 Tidskriftsartikel (refereegranskat)
25.	Ekstedt, Mattias, et al. (författare) Statins in non-alcoholic fatty liver disease and chronically elevated liver enzymes : a histopathological follow-up study. 2007 Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 47:1, s. 135-141 Tidskriftsartikel (refereegranskat)abstract Background/Aims: The effect of statins on hepatic histology in non-alcoholic fatty liver disease (NAFLD) is not known. This study explores hepatic histology in NAFLD patients before and after initiation of statin therapy and compares histological outcome with NAFLD patients who had not been prescribed statins. Methods: Sixty-eight NAFLD patients were re-evaluated. Follow-up ranged from 10.3 to 16.3 years. Subjects were clinically investigated and a repeat liver biopsy was obtained. No patient was taking statins at baseline while 17 patients were treated with statins at follow-up. Results: At baseline, patients that later were prescribed statins had significantly higher BMI and more pronounced hepatic steatosis. At follow-up patients on medication with statins continued to have significantly higher BMI. Diabetes was significantly more common among patients on medication with statins and they had significantly more pronounced insulin resistance. However, they exhibited a significant reduction of liver steatosis at follow-up as opposed to patients not taking statins. Despite exhibiting a high risk profile for progression of liver fibrosis, only four patients on statin treatment progressed in fibrosis stage. Conclusions: Statins can be prescribed in patients with elevated liver enzymes because of NAFLD.
26.	Ekstedt, Mattias, 1976-, et al. (författare) The clinical relevance of the Nonalcoholic Fatty Liver Disease Activity Score (NAS) in predicting fibrosis progression 2008 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Objective: The NAFLD activity score (NAS) is a newly proposed system to grade the necroinflammatory activity in liver biopsies of NAFLD patients. This study evaluates the usefulness of the NAS in predicting clinical deterioration and fibrosis progression in NAFLD. Methods: One hundred and twenty-nine patients with biopsy proven NAFLD were included in a long-term histological follow-up study. Clinical and histological course were compared between NASH, “borderline NASH”, and “not NASH” patients. Significant fibrosis progression in NAFLD was defined as progression of more than one fibrosis stage or development of end-stage liver disease during follow-up. Results: Eighty-eight patients accepted re-evaluation and 68 underwent repeat liver biopsy. Mean time between biopsies was 13.8 ± 1.2 years (range 10.3-16.3). At baseline, NASH was diagnosed in 2 (1.6%) patients, and at follow-up, in 1 (1.5%) patient. A trend towards higher baseline NAS was seen in patients (n = 7) that developed end-stage liver disease (3.1 ± 0.9 vs. 2.4 ± 1.0; P = 0.062). Baseline NAS was significantly higher in patients with progressive fibrosis (2.9 ± 0.9 vs. 2.2 ± 0.9; P = 0.017), and NAS was independently associated with significant fibrosis progression tested in a multivariate analysis (P = 0.023). However, 18% of patients without NASH progressed significantly in fibrosis stage. Conclusion: Although the NAS is independently associated with future risk of progressive fibrosis in NAFLD, the clinical usefulness of the score is limited due to the significant overlap in clinical development between NAS-score groups.
27.	Ericson, E., et al. (författare) Hepatic patatin-like phospholipase domain-containing 3 levels are increased in I148M risk allele carriers and correlate with NAFLD in humans 2022 Ingår i: Hepatology communications.. - : Ovid Technologies (Wolters Kluwer Health). - 2471-254X. ; 6:10, s. 2689-2701 Tidskriftsartikel (refereegranskat)abstract In nonalcoholic fatty liver disease (NAFLD) the patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 variant is a contributor. In mice, the Pnpla3 148M variant accumulates on lipid droplets and probably leads to sequestration of a lipase cofactor leading to impaired mobilization of triglycerides. To advance our understanding of the localization and abundance of PNPLA3 protein in humans, we used liver biopsies from patients with NAFLD to investigate the link to NAFLD and the PNPLA3 148M genotype. We experimentally qualified an antibody against human PNPLA3. Hepatic PNPLA3 protein fractional area and localization were determined by immunohistochemistry in biopsies from a well-characterized NAFLD cohort of 67 patients. Potential differences in hepatic PNPLA3 protein levels among patients related to degree of steatosis, lobular inflammation, ballooning, and fibrosis, and PNPLA3 I148M gene variants were assessed. Immunohistochemistry staining in biopsies from patients with NAFLD showed that hepatic PNPLA3 protein was predominantly localized to the membranes of small and large lipid droplets in hepatocytes. PNPLA3 protein levels correlated strongly with steatosis grade (p = 0.000027) and were also significantly higher in patients with lobular inflammation (p = 0.009), ballooning (p = 0.022), and significant fibrosis (stage 2-4, p = 0.014). In addition, PNPLA3 levels were higher in PNPLA3 rs738409 148M (CG, GG) risk allele carriers compared to 148I (CC) nonrisk allele carriers (p = 0.0029). Conclusion: PNPLA3 protein levels were associated with increased hepatic lipid content and disease severity in patients with NAFLD and were higher in PNPLA3 rs738409 (148M) risk allele carriers. Our hypothesis that increased hepatic levels of PNPLA3 may be part of the pathophysiological mechanism of NAFLD is supported.
28.	Farahat, Taghreed M., et al. (författare) The paradigm shift from NAFLD to MAFLD: A global primary care viewpoint 2022 Ingår i: Liver international (Print). - : WILEY. - 1478-3223 .- 1478-3231. ; 42:6, s. 1259-1267 Forskningsöversikt (refereegranskat)abstract n/a
29.	Forsgren, Mikael F, 1983-, et al. (författare) Biomarkers of liver fibrosis : prospective comparison of multimodal magnetic resonance, serum algorithms and transient elastography. 2020 Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 55:7, s. 848-859 Tidskriftsartikel (refereegranskat)abstract BACKGROUND AND AIMS: Accurate biomarkers for quantifying liver fibrosis are important for clinical practice and trial end-points. We compared the diagnostic performance of magnetic resonance imaging (MRI), including gadoxetate-enhanced MRI and 31P-MR spectroscopy, with fibrosis stage and serum fibrosis algorithms in a clinical setting. Also, in a subset of patients, MR- and transient elastography (MRE and TE) was evaluated when available.METHODS: Patients were recruited prospectively if they were scheduled to undergo liver biopsy on a clinical indication due to elevated liver enzyme levels without decompensated cirrhosis. Within a month of the clinical work-up, an MR-examination and liver needle biopsy were performed on the same day. Based on late-phase gadoxetate-enhanced MRI, a mathematical model calculated hepatobiliary function (relating to OATP1 and MRP2). The hepatocyte gadoxetate uptake rate (KHep) and the normalised liver-to-spleen contrast ratio (LSC_N10) were also calculated. Nine serum fibrosis algorithms were investigated (GUCI, King's Score, APRI, FIB-4, Lok-Index, NIKEI, NASH-CRN regression score, Forns' score, and NAFLD-fibrosis score).RESULTS: The diagnostic performance (AUROC) for identification of significant fibrosis (F2-4) was 0.78, 0.80, 0.69, and 0.78 for MRE, TE, LSC_N10, and GUCI, respectively. For the identification of advanced fibrosis (F3-4), the AUROCs were 0.93, 0.84, 0.81, and 0.82 respectively.CONCLUSION: MRE and TE were superior for non-invasive identification of significant fibrosis. Serum fibrosis algorithms developed for specific liver diseases are applicable in this cohort of diverse liver diseases aetiologies. Gadoxetate-MRI was sufficiently sensitive to detect the low function losses associated with fibrosis. None was able to efficiently distinguish between stages within the low fibrosis stages.Lay summaryExcessive accumulation of scar tissue, fibrosis, in the liver is an important aspect in chronic liver disease. To replace the invasive needle biopsy, we have explored non-invasive methods to assess liver fibrosis. In our study we found that elastographic methods, which assess the mechanical properties of the liver, are superior in assessing fibrosis in a clinical setting. Of interest from a clinical trial point-of-view, none of the tested methods was sufficiently accurate to distinguish between adjacent moderate fibrosis stages.
30.	Forsgren, Mikael, et al. (författare) Model-inferred mechanisms of liver function from magnetic resonance imaging data : Validation and variation across a clinically relevant cohort 2019 Ingår i: PloS Computational Biology. - San Francisco, CA, United States : Public Library of Science. - 1553-734X .- 1553-7358. ; 15:6 Tidskriftsartikel (refereegranskat)abstract Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.Author summaryBeing able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.
31.	Forsgren, Mikael, et al. (författare) Prospective evaluation of liver steatosis comparing stereological point-counting biopsy analysis and 1H MRS 2012 Konferensbidrag (övrigt vetenskapligt/konstnärligt)
32.	Franzén, Lennart E, et al. (författare) Semiquantitative evaluation overestimates the degree of steatosis in liver biopsies : a comparison to stereological point counting. 2005 Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 18:7, s. 912-916 Tidskriftsartikel (refereegranskat)abstract The degree of steatosis in liver biopsies is usually assessed by a morphological semiquantitative approach in which the histopathologist uses a four-graded scale: 0-3 or none, slight, moderate and severe. Scores 1-3 are considered to correspond to fat deposition in <33, 33-66 and >66% of the hepatocytes. There is a considerable inter- and intra-individual variation in such scoring methods and a more standardized and quantitative approach is preferable. In the present study, we compare the semiquantitative technique with the stereological point counting method in the assessment of hepatic steatosis. A total of 75 archived liver needle biopsies were used. They were selected according to the original routine diagnosis of slight, moderate or severe steatosis. In all, 10 randomly selected images from each biopsy were digitized into a computer, a point grid lattice was superimposed and the number of hits on fat globules was counted. A pathologist scored the specimens in a four-graded scale as described above. The mean liver biopsy area (volume) with fat in hepatocytes was 2.2% for grade 1, 9.2% for grade 2 and 23.1% for grade 3. The kappa value for the semiquantitative estimates was 0.71 for the unweigthed kappa and 0.87 for weighted kappa. The intraclass correlation coefficient (ICC) was 0.99 for images counted twice and 0.95 when two sets of images were captured from the same biopsy. These ICCs indicate excellent agreement and above that of the semiquantitative estimates. In conclusion, the area/volume of fat content of the hepatocytes is greatly overemphasized in semiquantitative estimation. Furthermore, the point counting technique has a better reproducibility than visual evaluation and should be preferred in estimates of liver steatosis in scientific studies and in clinical contexts when the amount of steatosis is important for treatment and prognosis, such as liver transplantation.
33.	Franzen, L., et al. (författare) Letter to the editor (multiple letter) 2005 Ingår i: Clinical Transplantation. - : Wiley. - 0902-0063 .- 1399-0012. ; 19:4, s. 571- Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
34.	Govaere, Olivier, et al. (författare) A proteo-transcriptomic map of non-alcoholic fatty liver disease signatures 2023 Ingår i: Nature Metabolism. - : NATURE PORTFOLIO. - 2522-5812. ; 5:4, s. 572-578 Tidskriftsartikel (refereegranskat)abstract Govaere et al. integrate circulating protein data from more than 300 patients with non-alcoholic fatty liver disease (NAFLD) with transcriptomics and develop a non-invasive diagnostics tool to identify patients with at-risk NAFLD based on body mass index, type 2 diabetes status and four circulating proteins. Non-alcoholic fatty liver disease (NAFLD) is a common, progressive liver disease strongly associated with the metabolic syndrome. It is unclear how progression of NAFLD towards cirrhosis translates into systematic changes in circulating proteins. Here, we provide a detailed proteo-transcriptomic map of steatohepatitis and fibrosis during progressive NAFLD. In this multicentre proteomic study, we characterize 4,730 circulating proteins in 306 patients with histologically characterized NAFLD and integrate this with transcriptomic analysis in paired liver tissue. We identify circulating proteomic signatures for active steatohepatitis and advanced fibrosis, and correlate these with hepatic transcriptomics to develop a proteo-transcriptomic signature of 31 markers. Deconvolution of this signature by single-cell RNA sequencing reveals the hepatic cell types likely to contribute to proteomic changes with disease progression. As an exemplar of use as a non-invasive diagnostic, logistic regression establishes a composite model comprising four proteins (ADAMTSL2, AKR1B10, CFHR4 and TREM2), body mass index and type 2 diabetes mellitus status, to identify at-risk steatohepatitis.
35.	Govaere, O., et al. (författare) Macrophage scavenger receptor 1 mediates lipid-induced inflammation in non-alcoholic fatty liver disease 2022 Ingår i: Journal of Hepatology. - : Elsevier BV. - 0168-8278 .- 1600-0641. ; 76:5, s. 1001-1012 Tidskriftsartikel (refereegranskat)abstract Background & Aims: Obesity-associated inflammation is a key player in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the role of macrophage scavenger receptor 1 (MSR1, CD204) remains incompletely understood. Methods: A total of 170 NAFLD liver biopsies were processed for transcriptomic analysis and correlated with clinicopathological features. Msr1-/- and wild-type mice were subjected to a 16-week high-fat and high-cholesterol diet. Mice and ex vivo human liver slices were treated with a monoclonal antibody against MSR1. Genetic susceptibility was assessed using genome-wide association study data from 1,483 patients with NAFLD and 430,101 participants of the UK Biobank. Results: MSR1 expression was associated with the occurrence of hepatic lipid-laden foamy macrophages and correlated with the degree of steatosis and steatohepatitis in patients with NAFLD. Mice lacking Msr1 were protected against diet-induced metabolic disorder, showing fewer hepatic foamy macrophages, less hepatic inflammation, improved dyslipidaemia and glucose tolerance, and altered hepatic lipid metabolism. Upon induction by saturated fatty acids, MSR1 induced a pro-inflammatory response via the JNK signalling pathway. In vitro blockade of the receptor prevented the accumulation of lipids in primary macrophages which inhibited the switch towards a pro-inflammatory phenotype and the release of cytokines such as TNF-ɑ. Targeting MSR1 using monoclonal antibody therapy in an obesity-associated NAFLD mouse model and human liver slices resulted in the prevention of foamy macrophage formation and inflammation. Moreover, we identified that rs41505344, a polymorphism in the upstream transcriptional region of MSR1, was associated with altered serum triglycerides and aspartate aminotransferase levels in a cohort of over 400,000 patients. Conclusions: Taken together, our data suggest that MSR1 plays a critical role in lipid-induced inflammation and could thus be a potential therapeutic target for the treatment of NAFLD. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is a chronic disease primarily caused by excessive consumption of fat and sugar combined with a lack of exercise or a sedentary lifestyle. Herein, we show that the macrophage scavenger receptor MSR1, an innate immune receptor, mediates lipid uptake and accumulation in Kupffer cells, resulting in liver inflammation and thereby promoting the progression of NAFLD in humans and mice. © 2021 The Authors
36.	Govaere, Olivier, et al. (författare) Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis 2020 Ingår i: Science Translational Medicine. - Washington, DC, United States : American Association for the Advancement of Science (AAAS). - 1946-6234 .- 1946-6242. ; 12:572 Tidskriftsartikel (refereegranskat)abstract The mechanisms that drive nonalcoholic fatty liver disease (NAFLD) remain incompletely understood. This large multicenter study characterized the transcriptional changes that occur in liver tissue across the NAFLD spectrum as disease progresses to cirrhosis to identify potential circulating markers. We performed high-throughput RNA sequencing on a discovery cohort comprising histologically characterized NAFLD samples from 206 patients. Unsupervised clustering stratified NAFLD on the basis of disease activity and fibrosis stage with differences in age, aspartate aminotransferase (AST), type 2 diabetes mellitus, and carriage of PNPLA3 rs738409, a genetic variant associated with NAFLD. Relative to early disease, we consistently identified 25 differentially expressed genes as fibrosing steatohepatitis progressed through stages F2 to F4. This 25-gene signature was independently validated by logistic modeling in a separate replication cohort (n = 175), and an integrative analysis with publicly available single-cell RNA sequencing data elucidated the likely relative contribution of specific intrahepatic cell populations. Translating these findings to the protein level, SomaScan analysis in more than 300 NAFLD serum samples confirmed that circulating concentrations of proteins AKR1B10 and GDF15 were strongly associated with disease activity and fibrosis stage. Supporting the biological plausibility of these data, in vitro functional studies determined that endoplasmic reticulum stress up-regulated expression of AKR1B10, GDF15, and PDGFA, whereas GDF15 supplementation tempered the inflammatory response in macrophages upon lipid loading and lipopolysaccharide stimulation. This study provides insights into the pathophysiology of progressive fibrosing steatohepatitis, and proof of principle that transcriptomic changes represent potentially tractable and clinically relevant markers of disease progression.
37.	Gruneau, Lina, et al. (författare) Cost-effectiveness analysis of noninvasive tests to identify advanced fibrosis in non-alcoholic fatty liver disease 2023 Ingår i: HEPATOLOGY COMMUNICATIONS. - : LIPPINCOTT WILLIAMS & WILKINS. - 2471-254X. ; 7:7 Tidskriftsartikel (refereegranskat)abstract Background: Advanced fibrosis is associated with end-stage liver disease (ESLD) and mortality in NAFLD. As treatments specifically targeted at NAFLD are lacking, patient management focuses on surveillance for early detection of complications related to end-stage liver disease. Although current and emerging diagnostic tools for the detection of advanced fibrosis are crucial for surveillance, their added value is unclear. The aim of this study was to evaluate the costs and health outcomes of noninvasive tests in patient management strategies for diagnosing advanced fibrosis in NAFLD patients. Method: A decision analytical model was developed to evaluate 13 patient management strategies, including a no-testing strategy and 12 diagnostic algorithms with noninvasive tests (fibrosis 4-score, enhanced liver fibrosis, vibration controlled transient elastography), and liver biopsy. Model inputs were synthesized from the literature and Swedish registries. Lifetime health care costs, life years, quality-adjusted life years, clinical outcomes, and incremental cost-effectiveness ratios were calculated for a cohort of 55-year-old patients diagnosed with NAFLD. Result: The cost per quality-adjusted life year was above (sic)50 000 for all diagnostic algorithms compared to no-testing. The cost per quality-adjusted life year of the most promising diagnostic algorithm (fibrosis 4-score, enhanced liver fibrosis, vibration controlled transient elastography, and liver biopsy) was similar to(sic)181 000 compared with no testing. Sensitivity analysis indicated that if treatment slowed down disease progression, the value of testing increased. Conclusion: The result questions the overall value of comprehensive diagnostic testing in a broad NAFLD population in current routine clinical care. The role of noninvasive tests may change if evidence-based treatments to slow down disease progression emerge.
38.	Gruneau, Lina, et al. (författare) Disease Progression Modeling for Economic Evaluation in Nonalcoholic Fatty Liver Disease-A Systematic Review 2023 Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 21:2, s. 283-298 Forskningsöversikt (refereegranskat)abstract BACKGROUND & AIMS: Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic con-sequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD.METHODS: A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies.RESULTS: Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively.CONCLUSIONS: The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments.
39.	Gummesson, Christina, et al. (författare) Entrustable professional activities (EPAs) for undergraduate medical education : development and exploration of social validity 2023 Ingår i: BMC Medical Education. - : BioMed Central (BMC). - 1472-6920. ; 23:1 Tidskriftsartikel (refereegranskat)abstract Background: The development of entrustable professional activities (EPAs) as a framework for work-based training and assessment in undergraduate medical education has become popular. EPAs are defined as units of a professional activity requiring adequate knowledge, skills, and attitudes, with a recognized output of professional labor, independently executable within a time frame, observable and measurable in its process and outcome, and reflecting one or more competencies. Before a new framework is implemented in a specific context, it is valuable to explore social validity, that is, the acceptability by relevant stakeholders.Aim: The aim of our work was to define Core EPAs for undergraduate medical education and further explore the social validity of the constructs.Method and material: In a nationwide collaboration, EPAs were developed using a modified Delphi procedure and validated according to EQual by a group consisting of teachers nominated from each of the seven Swedish medical schools, two student representatives, and an educational developer (n = 16). In the next step, social validity was explored in a nationwide survey. The survey introduced the suggested EPAs. For each EPA, the importance of the EPA was rated, as was the rater’s perception of the present graduates’ required level of supervision when performing the activity. Free-text comments were also included and analyzed.Results: Ten Core EPAs were defined and validated. The validation scores for EQual ranged from 4.1 to 4.9. The nationwide survey had 473 responders. All activities were rated as “important” by most responders, ranging from 54 to 96%. When asked how independent current graduates were in performing the ten activities, 6 to 35% reported “independent”. The three themes of the free text comments were: ‘relevant target areas and content’; ‘definition of the activities’; and ‘clinical practice and learning’.Conclusion: Ten Core EPAs were defined and assessed as relevant for Swedish undergraduate medical education. There was a consistent gap between the perceived importance and the certainty that the students could perform these professional activities independently at the time of graduation. These results indicate that the ten EPAs may have a role in undergraduate education by creating clarity for all stakeholders.
40.	Hagstrom, Hannes, et al. (författare) Accuracy of Noninvasive Scoring Systems in Assessing Risk of Death and Liver-Related Endpoints in Patients With Nonalcoholic Fatty Liver Disease 2019 Ingår i: Clinical Gastroenterology and Hepatology. - : Saunders Elsevier. - 1542-3565 .- 1542-7714. ; 17:6, s. 1148-1156.e4 Tidskriftsartikel (refereegranskat)abstract Background and AimsSeveral non-invasive scoring systems have been developed to determine risk of advanced fibrosis in non-alcoholic fatty liver disease (NAFLD). We examined the association between 4 scoring systems and incident severe liver disease and overall mortality in a large cohort of patients with biopsy-proven NAFLD.MethodsWe performed a retrospective analysis of data from 646 patients with biopsy-proven NAFLD, recruited from 2 hospitals in Sweden, from 1971 through 2009. The NAFLD fibrosis score (NFS), FIB-4, APRI, and BARD scores were calculated at the time of the liver biopsy. Based on each score, patients were assigned to categories of low, intermediate, or high risk for advanced fibrosis. Overall mortality and severe liver disease (cirrhosis, decompensated liver disease, liver failure, or hepatocellular carcinoma) were ascertained through linkage with national registers until the end of 2014. Cox regression, area under the receiver operating characteristic (AUROC) curve, and C-statistic analyses were used to study the predictive capacity of each scoring system.ResultsDuring a mean follow-up time of 19.9±8.7 years, there were 214 deaths and 76 cases of severe liver disease. For overall mortality, AUROC curve values were: NFS, 0.72 (95% CI, 0.68–0.76); FIB-4, 0.72 (95% CI, 0.68–0.76); BARD, 0.62 (95% CI, 0.58–0.66); and APRI, 0.52 (95% CI, 0.47–0.57). For severe liver disease, AUROC curve values were: NFS, 0.72 (95% CI, 0.66–0.78); FIB-4, 0.72 (95% CI, 0.66–0.79); BARD, 0.62 (95% CI, 0.55–0.69); APRI, 0.69 (95% CI, 0.63–0.76). C-statistics for all scores were of moderate capacity to predict outcomes.ConclusionsIn a retrospective analysis of data from 646 patients with biopsy-proven NAFLD, we found the NFS and the FIB-4 scores to most accurately determine risk of overall death or severe liver disease. However, the AUROC values for these scoring systems are not high enough for use in the clinic; new systems are needed to determine prognoses of patients with NAFLD.
41.	Hagstrom, H, et al. (författare) Bariatric Surgery Versus Standard Obesity Treatment and the Risk of Severe Liver Disease: Data From the Swedish Obese Subjects Study 2021 Ingår i: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. - Philadelphia, PA, United States : Elsevier BV. - 1542-7714 .- 1542-3565. ; 19:12, s. 2675- Tidskriftsartikel (refereegranskat)
42.	Hagstrom, Hannes, et al. (författare) Cardiovascular risk factors in non-alcoholic fatty liver disease 2019 Ingår i: Liver international (Print). - : WILEY. - 1478-3223 .- 1478-3231. ; 39:1, s. 197-204 Tidskriftsartikel (refereegranskat)abstract Background amp; Aims Patients with non-alcoholic fatty liver disease (NAFLD) are at an increased risk for cardiovascular disease (CVD). It is unclear whether histological variables may help predict CVD risk. We evaluated histology and traditional CV risk factors as predictors of CVD outcomes in a large NAFLD cohort. Methods We included 603 biopsy-proven NAFLD patients free of baseline CVD and matched these (1:10, by age, sex and municipality) to 6269 population controls. All individuals were cross-linked to national registries to ascertain incident CVD events, defined as acute ischaemic heart disease or stroke. The presence of CV risk factors and liver histology were available in NAFLD patients only. Cox regression models were used to estimate hazard ratios (HR) for incident CVD. Results During a mean follow-up of 18.6 years, 168 (28%) of NAFLD patients and 1325 (21%) of controls experienced a CVD event (HR 1.54, 95%CI 1.30-1.83). Within the NAFLD cohort, age, male sex, type 2 diabetes, smoking and triglycerides were associated with risk of CVD. Taking these CV risk factors into account, no histological parameter, including presence of NASH and fibrosis stage, were associated with incident CVD. Conclusions Patients with NAFLD are at an increased risk for CVD compared to matched controls, but histological parameters do not seem to independently predict this risk.
43.	Hagstrom, H., et al. (författare) Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers 2021 Ingår i: Liver International. - : Wiley. - 1478-3223 .- 1478-3231. ; 41:3, s. 545-553 Tidskriftsartikel (refereegranskat)abstract Background & Aims Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. Methods We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinson's disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. Results Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.
44.	Hagstrom, H, et al. (författare) Risk for hepatic and extra-hepatic outcomes in nonalcoholic fatty liver disease 2022 Ingår i: Journal of internal medicine. - Chichester, UK : Wiley. - 1365-2796 .- 0954-6820. ; 292:2, s. 177-189 Tidskriftsartikel (refereegranskat)
45.	Hagstrom, Hannes, et al. (författare) Serum levels of endotrophin are associated with nonalcoholic steatohepatitis 2021 Ingår i: Scandinavian Journal of Gastroenterology. - : Taylor & Francis. - 0036-5521 .- 1502-7708. ; 56:4, s. 437-442 Tidskriftsartikel (refereegranskat)abstract Background and aimsThere are no currently available biomarkers that can accurately indicate the presence of non-alcoholic steatohepatitis (NASH). We investigated the association between endotrophin, a cleavage product of collagen type 6α3, and disease severity in patients with non-alcoholic fatty liver disease (NAFLD).MethodsWe measured serum endotrophin levels in 211 patients with NAFLD and nine healthy controls. Liver biopsy data was available for 141 (67%) of the patients. Associations between endotrophin and the presence of NASH and advanced fibrosis were investigated alone and in combination with standard clinical parameters using logistic regression.ResultsA total of 211 patients were enrolled in this study, consisting of 108 (51%) men and 103 (49%) women with a mean age of 55.6 years. 58 (27%) of the patients had advanced fibrosis. Of those with biopsy data, 87 (62%) had NASH. Serum levels of endotrophin were significantly higher in patients with NAFLD than those in healthy controls (37[±12] vs. 17[±7] ng/mL, p<.001). Serum levels of endotrophin were also significantly higher in patients with NASH than in those without NASH (40[±12] vs. 32[±13] ng/mL, p<.001). A model using age, sex, body mass index and levels of alanine aminotransferase (ALT), glucose and endotrophin effectively predicted the presence of NASH in a derivation (AUROC 0.83, 95%CI = 0.74–0.92) and validation cohort (AUROC 0.71, 95%CI = 0.54–0.88). There was no significant association between serum levels of endotrophin and advanced fibrosis.ConclusionsThese data suggest that serum endotrophin could be a valuable biomarker for diagnosing NASH, but not for detecting advanced fibrosis in NAFLD.
46.	Hagström, H, et al. (författare) 99% of patients with NAFLD meet MASLD criteria and natural history is therefore identical 2024 Ingår i: Journal of hepatology. - : Elsevier. - 1600-0641 .- 0168-8278. ; 80:2, s. e76-e77 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
47.	Hagström, Hannes, et al. (författare) Elevated serum ferritin is associated with increased mortality in non-alcoholic fatty liver disease after 16 years of follow-up 2016 Ingår i: Liver international (Print). - : John Wiley & Sons. - 1478-3223 .- 1478-3231. ; 36:11, s. 1688-1695 Tidskriftsartikel (refereegranskat)abstract 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.
48.	Hagström, Hannes, et al. (författare) Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD 2017 Ingår i: Journal of Hepatology. - : ELSEVIER SCIENCE BV. - 0168-8278 .- 1600-0641. ; 67:6, s. 1265-1273 Tidskriftsartikel (refereegranskat)abstract Background amp; Aims: Non-alcoholic fatty liver disease (NAFLD) is very common in the general population, but identifying patients with increased risk of mortality and liver-specific morbidity remains a challenge. Non-alcoholic steatohepatitis (NASH) is thought to enhance this risk; therefore, resolution of NASH is a major endpoint in current pharmacologic studies. Herein, we aim to investigate the long-term prognosis of a large cohort of NAFLD patients, and to study the specific effect of NASH and fibrosis stage on prognosis. Methods: We conducted a retrospective cohort study of 646 biopsy-proven NAFLD patients. Each case was matched for age, sex and municipality to ten controls. Outcomes on mortality and severe liver disease, defined as cirrhosis, liver decompensation/failure or hepatocellular carcinoma, were evaluated using population-based registers. Cox regression models adjusted for age, sex and type 2 diabetes were used to examine the long-term risk according to fibrosis stage. Likelihood ratio tests were used to assess whether adding NASH to these models increased the predictive capacity. Laplace regression was used to estimate the time to severe liver disease according to stage of fibrosis. Results: During a follow-up of mean 20 years (range 0-40) equivalent to 139,163 person-years, 12% of NAFLD patients and 2.2% of controls developed severe liver disease (p amp;lt; 0.001). Compared to controls, the risk of severe liver disease increased per stage of fibrosis (hazard ratio ranging from 1.9 in F0 to 104.9 in F4). Accounting for the presence of NASH did not change these estimates significantly (likelihood ratio test amp;gt; 0.05 for all stages of fibrosis). Similar results were seen for overall mortality. The lower end of the 95% confidence interval for the 10th percentile of time to development of severe liver disease was 22-26 years in F0-1, 9.3 years in F2, 2.3 years in F3, and 0.9 years to liver decompensation in F4. Conclusions: In this, the largest ever study of biopsy-proven NAFLD, the presence of NASH did not increase the risk of liver-specific morbidity or overall mortality. Knowledge of time to development of severe liver disease according to fibrosis stage can be used in individual patient counselling and for public health decisions. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
49.	Hagström, Hannes, et al. (författare) Health Care Costs of Patients With Biopsy-Confirmed Nonalcoholic Fatty Liver Disease Are Nearly Twice Those of Matched Controls 2020 Ingår i: Clinical Gastroenterology and Hepatology. - : ELSEVIER SCIENCE INC. - 1542-3565 .- 1542-7714. ; 18:7, s. 1592- Tidskriftsartikel (refereegranskat)abstract BACKGROUND & AIMS: Data on healthcare resource use and costs associated with nonalcoholic fatty liver disease (NAFLD) in clinical practice are lacking. We compared real-life healthcare costs of patients with NAFLD to matched controls. METHODS: We performed a retrospective study of 646 patients with biopsy-proven NAFLD in Sweden from 1971 through 2009. Each patient was matched for age, sex, and county of residence with 10 persons from the general population (controls). We retrieved all healthcare contacts through Dec 31, 2014 from national registers. Unit costs were assigned to arrive at a total healthcare cost (in USD [$]) per study subject. RESULTS: During a mean follow-up of 19.9 years, we recorded a mean of 0.27 hospitalizations per year for patients with NAFLD vs 0.16 for controls (P <.001). This corresponded to an incremental cost of $635 per year for patients with NAFLD. Patients with NAFLD had a higher mean use of outpatient care visits: 1.46 contacts per year compared with 0.86 per year in controls, corresponding to $255 in additional costs (P <.001). Total costs incurred by patients with stage 3-4 fibrosis were higher than by patients with fibrosis stage 0-2 (mean annual costs, $4397 vs $629). Cumulative costs were higher for all stages of fibrosis compared to controls. CONCLUSIONS: Healthcare costs are nearly twice as high in patients with NAFLD than in matched controls. This is mostly attributable to higher costs for hospitalizations, but also to more outpatient visits. Patients with advanced fibrosis had the highest costs.
50.	Hagström, Hannes, et al. (författare) Low to moderate lifetime alcohol consumption is associated with less advanced stages of fibrosis in non-alcoholic fatty liver disease 2017 Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 52:2, s. 159-165 Tidskriftsartikel (refereegranskat)abstract Background and aim: Moderate alcohol consumption has been associated with a lower risk of disease severity in non-alcoholic fatty liver disease (NAFLD). It is unclear if this reflects current or lifetime drinking, or can be attributed to confounders such as diet and exercise. We evaluated the impact of lifetime alcohol consumption on fibrosis severity in NAFLD. Methods: We prospectively enrolled 120 subjects with biopsy-proven NAFLD and through detailed questionnaires examined lifetime alcohol consumption, diet and physical activity. Main outcome measures were odds ratios (OR) for fibrosis stage, calculated through ordinal regression after adjustment for body mass index, diabetes mellitus type 2, smoking and age at biopsy. A biomarker for recent alcohol consumption, phosphatidyl ethanol (PEth) was sampled. Results: An increase in median weekly alcohol consumption to a maximum of 13 drinks per week was associated with lower fibrosis stage (adjusted OR for each incremental unit, 0.86; 95% CI, 0.76-0.97; p = .017). The lowest risk for fibrosis was found with the lowest odds seen in the top quartile of alcohol consumption (aOR 0.23; 95% CI 0.08-0.66; p = .006). Adding soft drink and coffee consumptions, and physical activity to the model did not change the estimates. Subjects with PEth >= 0.3 mu mol/L had higher ORs for a higher fibrosis stage (aOR 2.77; 95% CI 1.01-7.59; p = .047). Conclusion: Lifetime alcohol consumption with up to 13 units per week is associated with lower fibrosis stage in NAFLD. Elevated PEth is associated with higher stages of fibrosis.

Skapa referenser, mejla, bekava och länka

Länka till träfflistan

Resultat 1-50 av 128

Avgränsa träffmängd

Typ av publikation: tidskriftsartikel (109); doktorsavhandling (6); forskningsöversikt (6); konferensbidrag (5); bokkapitel (2)

Typ av innehåll: refereegranskat (105); övrigt vetenskapligt/konstnärligt (23)

Författare/redaktör: Ekstedt, Mattias (92); Kechagias, Stergios (62); Nasr, Patrik (35); Ekstedt, Mattias, 19 ... (29); Lundberg, Peter (15); Hagström, Hannes (15); visa fler...; Dahlqvist Leinhard, ... (14); Hultcrantz, Rolf (14); Nasr, Patrik, 1987- (13); Anstee, Quentin M. (13); Hagstrom, Hannes (12); Bugianesi, Elisabett ... (12); Ratziu, Vlad (11); Stal, Per (10); Tiniakos, Dina (10); Kechagias, Stergios, ... (10); Bedossa, Pierre (9); Stål, Per (9); Boursier, Jerome (9); Aithal, Guruprasad P ... (8); Petta, Salvatore (8); Ignatova, Simone (8); Dahlström, Nils (8); Forsgren, Mikael (7); Allison, Michael (7); Yki-Jarvinen, Hannel ... (7); Dufour, Jean-Francoi ... (7); Francque, Sven (7); Lundberg, Peter, 195 ... (6); Hellman, Jarl (6); Gummesson, Christina (6); Alm, Stina (6); Cedersund, Gunnar (6); Govaere, Olivier (6); Valenti, Luca (6); Romero-Gomez, Manuel (6); Blomdahl, Julia (6); Franzén, Lennart E (6); Abrandt Dahlgren, Ma ... (5); Rosengren, Björn (5); Daly, Ann K. (5); Shang, Ying (5); Cockell, Simon (5); Clement, Karine (5); Schattenberg, Joern ... (5); Möller, Riitta (5); Mathiesen, Ulrik L (5); Karsdal, Morten (5); Cortez-Pinto, Helena (5); Wonders, Kristy (5); visa färre...

Lärosäte: Linköpings universitet (118); Karolinska Institutet (33); Göteborgs universitet (11); Örebro universitet (11); Uppsala universitet (8); Umeå universitet (5); visa fler...; Lunds universitet (5); Sveriges Lantbruksuniversitet (2); Jönköping University (1); Malmö universitet (1); visa färre...

Språk: Engelska (123); Svenska (5)

Forskningsämne (UKÄ/SCB): Medicin och hälsovetenskap (101); Samhällsvetenskap (9); Naturvetenskap (3); Lantbruksvetenskap (2); Teknik (1)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se

Stäng

Kopiera och spara länken för att återkomma till aktuell vy