7 results on '"Tushuizen, Maarten E."'
Search Results
2. Non-Parenchymal Cells and the Extracellular Matrix in Hepatocellular Carcinoma in Non-Alcoholic Fatty Liver Disease.
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van Son, Koen C., Verschuren, Lars, Hanemaaijer, Roeland, Reeves, Helen, Takkenberg, R. Bart, Drenth, Joost P. H., Tushuizen, Maarten E., and Holleboom, Adriaan G.
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NON-alcoholic fatty liver disease , *DISEASE incidence , *IMMUNE system , *COMPARATIVE studies , *EXTRACELLULAR space , *CELL lines , *LIVER cells , *HEPATOCELLULAR carcinoma - Abstract
Simple Summary: The incidence of hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has increased in recent years. Compared to HCC caused by other chronic liver diseases, NAFLD-related HCC is often detected later, because it more commonly arises before cirrhosis has occurred. Because of this late diagnosis, NAFLD-related HCC is often more advanced at time of diagnosis, resulting in fewer curative treatment options. Most research in the pathogenesis of HCC has focused on the disease processes in hepatocytes, the most abundant type of liver cells. However, other cell types, such as cells of the immune system and cells that regulate connective tissue formation, also play an important role in the development of NAFLD-related HCC, both by contributing to the development of HCC itself and by interfering with the immune system's ability to attack cancer cells. In this paper, we review the role of different cell types in the development of NAFLD-related HCC. Hepatocellular carcinoma (HCC) in the setting of non-alcoholic fatty liver disease (NAFLD)-related cirrhosis and even in the pre-cirrhotic state is increasing in incidence. NAFLD-related HCC has a poor clinical outcome as it is often advanced at diagnosis due to late diagnosis and systemic treatment response is poor due to reduced immune surveillance. Much of the focus of molecular research has been on the pathological changes in hepatocytes; however, immune cells, hepatic stellate cells, liver sinusoidal endothelial cells and the extracellular matrix may play important roles in the pathogenesis of NAFLD-related HCC as well. Here, we review the role of non-parenchymal cells in the liver in the pathogenesis of HCC in the context of NAFLD-NASH, with a particular focus on the innate and the adaptive immune system, fibrogenesis and angiogenesis. We review the key roles of macrophages, hepatic stellate cells (HSCs), T cells, natural killer (NK) cells, NKT cells and liver sinusoidal endothelial cells (LSECs) and the role of the extracellular matrix in hepatocarcinogenesis within the steatotic milieu. [ABSTRACT FROM AUTHOR]
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- 2023
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3. FGF21 protects against hepatic lipotoxicity and macrophage activation to attenuate fibrogenesis in nonalcoholic steatohepatitis.
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Cong Liu, Schönke, Milena, Spoorenberg, Borah, Lambooij, Joost M., van der Zande, Hendrik J. P., Enchen Zhou, Tushuizen, Maarten E., Andreasson, Anne-Christine, Park, Andrew, Oldham, Stephanie, Uhrbom, Martin, Ahlstedt, Ingela, Yasuhiro Ikeda, Wallenius, Kristina, Xiao-Rong Peng, Guigas, Bruno, Boon, Mariëtte R., Yanan Wang, and Rensen, Patrick C. N.
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MACROPHAGE activation , *NON-alcoholic fatty liver disease , *HYPERTROPHIC scars , *FATTY acid oxidation , *HIGH cholesterol diet , *KUPFFER cells , *FIBROBLAST growth factors - Abstract
Analogues of the hepatokine fibroblast growth factor 21 (FGF21) are in clinical development for type 2 diabetes and nonalcoholic steatohepatitis (NASH) treatment. Although their glucose-lowering and insulin-sensitizing effects have been largely unraveled, the mechanisms by which they alleviate liver injury have only been scarcely addressed. Here, we aimed to unveil the mechanisms underlying the protective effects of FGF21 on NASH using APOE*3-Leiden. CETP mice, a well-established model for human-like metabolic diseases. Liver-specific FGF21 overexpression was achieved in mice, followed by administration of a high-fat high-cholesterol diet for 23 weeks. FGF21 prevented hepatic lipotoxicity, accompanied by activation of thermogenic tissues and attenuation of adipose tissue inflammation, improvement of hyperglycemia and hypertriglyceridemia, and upregulation of hepatic programs involved in fatty acid oxidation and cholesterol removal. Furthermore, FGF21 inhibited hepatic inflammation, as evidenced by reduced Kupffer cell (KC) activation, diminished monocyte infiltration, and lowered accumulation of monocyte-derived macrophages. Moreover, FGF21 decreased lipid- and scar-associated macrophages, which correlated with less hepatic fibrosis as demonstrated by reduced collagen accumulation. Collectively, hepatic FGF21 overexpression limits hepatic lipotoxicity, inflammation, and fibrogenesis. Mechanistically, FGF21 blocks hepatic lipid influx and accumulation through combined endocrine and autocrine signaling, respectively, which prevents KC activation and lowers the presence of lipid- and scar-associated macrophages to inhibit fibrogenesis. [ABSTRACT FROM AUTHOR]
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- 2023
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4. Improvement of non-invasive tests of liver steatosis and fibrosis as indicators for non-alcoholic fatty liver disease in type 2 diabetes mellitus patients with elevated cardiovascular risk profile using the PPAR-α/γ agonist aleglitazar.
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Grobbee, Esmée J., de Jong, Vivian D., Schrieks, Ilse C., Tushuizen, Maarten E., Holleboom, Adriaan G., Tardif, Jean-Claude, Lincoff, A. Michael, Schwartz, Gregory G., Castro Cabezas, Manuel, and Grobbee, Diederick E.
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NON-alcoholic fatty liver disease , *HEPATIC fibrosis , *TYPE 2 diabetes , *CARDIOVASCULAR diseases risk factors , *PEOPLE with diabetes - Abstract
Background: Peroxisome proliferator-activated receptor (PPAR) agonists may have favorable outcomes on non-alcoholic fatty liver disease. This study serves as proof of concept to evaluate whether dual PPAR-α/γ agonists improve non-invasive tests of liver steatosis and fibrosis. Methods: This is a post-hoc analysis of a randomized, double-blind, placebo-controlled, multi-center trial comprising 7226 patients with type 2 diabetes mellitus and recent coronary artery disease randomized to receive aleglitazar, a PPAR-α/γ agonists, or placebo for two years. Main outcomes were change in non-invasive tests for liver steatosis and fibrosis: Liver Fat Score (LFS), Liver Accumulation Product (LAP), Fibrosis-4 (FIB-4), and NAFLD Fibrosis Score (NFS). Results: LFS, LAP and FIB-4 decreased upon treatment, whereas scores in the placebo group remained the same or increased (P<0.001). NFS responded differently but remained consistently lower than placebo. In the treatment group more participants shifted to a lower FIB-4 and NFS category, or improved in respect to the LAP cut-off values compared to the placebo group (P<0.001 for FIB-4 and LAP, P<0.004 for NFS). LFS had a low discriminative power in this study. Conclusion: This post-hoc analysis showed improvement of non-invasive tests of liver steatosis and fibrosis after starting dual PPAR-α/γ agonist treatment, adding to the evidence that this pathway has potential in non-alcoholic fatty liver disease treatment. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Evaluation of nonalcoholic fatty liver disease (NAFLD) in severe obesity using noninvasive tests and imaging techniques.
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Theel, Willy, Boxma‐de Klerk, Bianca M., Dirksmeier‐Harinck, Femme, van Rossum, Elisabeth F. C., Kanhai, Danny A., Apers, Jan, van Dalen, Bas M., de Knegt, Robert J., Holleboom, Anthony G., Tushuizen, Maarten E., Grobbee, Diederick E., Wiebolt, Janneke, and Castro Cabezas, Manuel
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NON-alcoholic fatty liver disease , *FATTY liver , *TYPE 2 diabetes , *HEPATIC fibrosis , *CARDIOVASCULAR diseases , *OBESITY - Abstract
Summary: The prevalence of nonalcoholic fatty liver disease (NAFLD) and the more severe and inflammatory type, nonalcoholic steatohepatitis (NASH), is increasing rapidly. Especially in high‐risk patients, that is those with obesity, metabolic syndrome, and type 2 diabetes mellitus, the prevalence of NAFLD can be as high as 80% while NASH may be present in 20% of these subjects. With the worldwide increase of obesity, it is most likely that these numbers will rise. Since advanced stages of NAFLD and NASH are strongly associated with morbidity and mortality—in particular, cardiovascular disease, liver cirrhosis, and hepatocellular carcinoma—it is of great importance to identify subjects at risk. A great variety of noninvasive tests has been published to diagnose NAFLD and NASH, especially using blood‐ and imaging‐based tests. Liver biopsy remains the gold standard for NAFLD/NASH. This review aims to summarize the different mechanisms leading to NASH and liver fibrosis, the different noninvasive liver tests to diagnose and evaluate patients with severe obesity. [ABSTRACT FROM AUTHOR]
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- 2022
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6. Acute Liver Injury and Acute Liver Failure following Bariatric Surgery.
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van Golen, Rowan F., de Waard, Nadine E., Moolenaar, Laura R., Inderson, Akin, Crobach, Stijn, Langers, Alexandra M.J., van Hoek, Bart, and Tushuizen, Maarten E.
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LIVER surgery , *BARIATRIC surgery , *LIVER failure , *LIVER injuries , *NON-alcoholic fatty liver disease , *NUTRITION counseling - Abstract
Bariatric surgery is the most effective treatment for obesity and improves several manifestations of the metabolic syndrome, including nonalcoholic fatty liver disease. Strict nutritional counseling after bariatric surgery is a key in realizing these outcomes. When postoperative nutrient intake or nutrient uptake is compromised, bariatric surgery can also lead to severe hepatic complications. Here, we describe 3 cases of acute liver injury and acute liver failure caused by bariatric surgery, all with different management strategies and outcomes. [ABSTRACT FROM AUTHOR]
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- 2022
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7. Systematic Review with Meta-Analyses: Diagnostic Accuracy of FibroMeter Tests in Patients with Non-Alcoholic Fatty Liver Disease.
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Van Dijk, Anne-Marieke, Vali, Yasaman, Mak, Anne Linde, Lee, Jenny, Tushuizen, Maarten E., Zafarmand, Mohammad Hadi, Anstee, Quentin M., Brosnan, M. Julia, Nieuwdorp, Max, Bossuyt, Patrick M., and Holleboom, Adriaan G.
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NON-alcoholic fatty liver disease , *RANDOM effects model , *SENSITIVITY & specificity (Statistics) , *ADULTS - Abstract
Early detection of liver fibrosis is crucial to select the correct care path for patients with non-alcoholic fatty liver disease (NAFLD). Here, we systematically review the evidence on the performance of FibroMeter versions in detecting different levels of fibrosis in patients with NAFLD. We searched four databases (Medline, Embase, the Cochrane library, and Web of Science) to find studies that included adults with NAFLD and biopsy-confirmed fibrosis (F1 to F4), compared with any version of FibroMeter. Two independent researchers screened the references, collected the data, and assessed the methodological quality of the included studies. We used a bivariate logit-normal random effects model to produce meta-analyses. From 273 references, 12 studies were eligible for inclusion, encompassing data from 3425 patients. Meta-analyses of the accuracy in detecting advanced fibrosis (F ≥ 3) were conducted for FibroMeter Virus second generation (V2G), NAFLD, and vibration controlled transient elaFS3stography (VCTE). FibroMeter VCTE showed the best diagnostic accuracy in detecting advanced fibrosis (sensitivity: 83.5% (95%CI 0.58–0.94); specificity: 91.1% (95%CI 0.89–0.93)), followed by FibroMeter V2G (sensitivity: 83.1% (95%CI 0.73–0.90); specificity: 84.4% (95%CI 0.62–0.95)) and FibroMeter NAFLD (sensitivity: 71.7% (95%CI 0.63–0.79); specificity: 82.8% (95%CI 0.71–0.91)). No statistically significant differences were found between the different FibroMeter versions. FibroMeter tests showed acceptable sensitivity and specificity in detecting advanced fibrosis in patients with NAFLD, but an urge to conduct head-to-head comparison studies in patients with NAFLD of the different FibroMeter tests remains. [ABSTRACT FROM AUTHOR]
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- 2021
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