Browsing by Author "Arrese, Marco"

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    A Global Survey of Physicians Knowledge About Nonalcoholic Fatty Liver Disease
    (2022) Younossi, Zobair M.; Ong, Janus P.; Takahashi, Hirokazu; Yilmaz, Yusuf; Hi, Yuichiro Eguc; El Kassas, Mohamed; Buti, Maria; Diago, Moises; Zheng, Ming-Hua; Fan, Jian-Gao; Yu, Ming-Lung; Wong, Vincent Wai-Sun; Alswat, Khalid; Chan, Wah-Kheong; Mendez-Sanchez, Nahum; Burra, Patrizia; Bugianesi, Elisabetta; Duseja, Ajay K.; George, Jacob; Papatheodoridis, George, V; Saeed, Hamid; Castera, Laurent; Arrese, Marco; Kugelmas, Marcelo; Romero-Gomez, Manuel; Alqahtani, Saleh; Ziayee, Mariam; Lam, Brian; Younossi, Issah; Racila, Andrei; Henry, Linda; Stepanova, Maria
    BACKGROUND & AIMS: Despite rapidly increasing nonalcoholic fatty liver disease (NAFLD) prevalence, providers' knowledge may be limited. We assessed NAFLD knowledge and associated factors among physicians of different specialties globally.
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    Chemical hypoxia induces pro-inflammatory signals in fat-laden hepatocytes and contributes to cellular crosstalk with Kupffer cells through extracellular vesicles
    (2020) Hernández Villanueva, Alejandra Andrea; Geng, Y.; Sepúlveda, R.; Solis López, Nancy de las Mercedes; Torres, J.; Arab Verdugo, Juan Pablo; Barrera Martínez, Francisco Javier; Cabrera, D.; Moshage, H.; Arrese, Marco
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    Effects of Japanese herbal medicine inchin-ko-to on endotoxin-induced cholestasis in the rat
    (MEXICAN ASSOC HEPATOLOGY, 2009) Pablo Arab, Juan; Ramirez, Carolina; Munoz, Pablo; Pizarro, Margarita; Solis, Nancy; Riquelme, Arnoldo; Arrese, Marco
    Background/Objective. Inchin-ko-to (ICKT) is an herbal medicine used in Japan to treat jaundice and liver fibrosis. We investigated the effect of oral ICKT supplementation on endotoxin-induced cholestasis in the rat. Material and methods. Lipopolysaccharide (LPS) injection (1 mg/kg body weight i.p.) was used as a model of sepsis-induced cholestasis. Bite flow, biliary bile salt secretion, biliary glutathione secretion and protein expression of the main hepatobiliary transporters Na(+)-taurocholate-cotransporting peptide (Ntcp), multidrug resistance protein 2 (Mrp2) and bile salt export pump (Bsep) were analyzed by conventional techniques in ICKT treated and non-treated animals. Results. Injection of LIDS induced a significant decrease of bite ftow (-24%), biliary bite salts (-40%) and glutathione excretion (-70%) as well as a significant decrease in Ntcp (-90%) and Mrp2 (-80%) protein levels. ICKT supplementation partially prevented the effects of LIPS determining a less intense reduction in bile flow (-10%), a normalization of glutathione excretion as well as a significant increase in Mrp2 protein levels to 60% of the levels observed in control animals. ICKT administration did not modify the effects of LPS on BS secretion or Ntcp protein levels. Conclusion. Our data show that oral. supplementation of ICKT partially prevents LPS-induced cholestasis by increasing Mrp2 protein levels and biliary glutathione excretion thus increasing bite salt-independent ftow.
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    MBOAT7 rs641738 Variant Is Not Associated with an Increased Risk of Hepatocellular Carcinoma in a Latin American Cohort
    (2023) Goble, Spencer; Akambase, Joseph; Prieto, Jhon; Balderramo, Domingo; Ferrer, Javier Diaz; Mattos, Angelo Z.; Arrese, Marco; Carrera, Enrique; Groothuismink, Zwier M. A.; Oliveira, Jeffrey; Boonstra, Andre; Debes, Jose D.
    Background The rs641738 C > T single-nucleotide polymorphism of MBOAT7 has been associated with hepatocellular carcinoma (HCC) and nonalcoholic fatty liver disease (NAFLD). Latin Americans have high rates of HCC and NAFLD, but no assessment between MBOAT7 and HCC has been performed in this population.Aims We provide the first assessment of the impact of MBOAT7 on HCC risk in Latin Americans.MethodsPatients were prospectively recruited into the ESCALON network, designed to collect samples from Latin American patients with HCC in 6 South American countries (Argentina, Ecuador, Brazil, Chile, Peru, and Colombia). A European cohort and the general Hispanic population of gnomAD database were included for comparison. Associations between HCC and MBOAT7 were evaluated using logistic regression.Results In total, 310 cases of HCC and 493 cases of cirrhosis without HCC were assessed. The MBOAT7 TT genotype was not predictive of HCC in Latin Americans (TT vs CC OR adjusted = 1.15, 95% CI 0.66-2.01, p = 0.610) or Europeans (TT vs CC OR adjusted = 1.20, 95% CI 0.59-2.43, p = 0.621). No significant association was noted on subgroup analysis for NAFLD, viral hepatitis, or alcohol-related liver disease. The TT genotype was increased in the NAFLD-cirrhosis cohort of Latin Americans compared to a non-cirrhotic NAFLD cohort (TT vs CC + CT OR = 2.75, 95% CI 1.10-6.87, p = 0.031).Conclusion The rs631738 C > T allele of MBOAT7 was not associated with increased risk of HCC in Latin Americans or Europeans. An increase in the risk of cirrhosis was noted with the TT genotype in Latin Americans with NAFLD.
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    Metabolic dysfunction and alcohol-related liver disease (MetALD): Position statement by an expert panel on alcohol-related liver disease
    (2025) Arab Verdugo, Juan Pablo; Díaz Piga, Luis Antonio; Rehm, Jürgen; Im, Gene; Arrese, Marco; Kamath, Patrick S.; Lucey, Michael R.; Mellinger, Jessica; Thiele, Maja; Thursz, Mark; Bataller, Ramon; Burton, Robyn; Chokshi, Shilpa; Francque, Sven M.; Krag, Aleksander; Lackner, Carolin; Lee, Brian; Liangpunsakul, Suthat; MacClain, Craig; Mandrekar, Pranoti; Mitchell, Mack C.; Morgan, Marsha Y.
    In this position statement, we explore the intricate relationship between alcohol intake and metabolic dysfunction in the context of the 2023 nomenclature update for steatotic liver disease (SLD). Recent and lifetime alcohol use should be accurately assessed in all patients with SLD to facilitate classification of alcohol use in grams of alcohol per week. Alcohol biomarkers (i.e., phosphatidylethanol), use of validated questionnaires (i.e. AUDIT-C [alcohol use disorders identification test consumption]), and collateral information from friends and relatives could help facilitate differentiation between alcohol-related liver disease (ALD) per se and liver disease with both metabolic and alcohol-related components (MetALD). Heavy alcohol use can contribute to cardiometabolic risk factors such as high blood pressure, hypertriglyceridaemia, and hyperglycaemia. As a result, caution should be exercised in the application of only one metabolic dysfunction criterion to diagnose MASLD, as suggested in the 2023 nomenclature document, particularly in individuals exceeding weekly alcohol use thresholds of 140 g for women and 210 g for men. This is particularly important in those individuals with isolated high blood pressure, hypertriglyceridaemia, or hyperglycaemia, where the disease process may be driven by alcohol itself. Additionally, metabolic dysfunction and alcohol use should be reassessed over time, especially after periods of change in risk factor exposure. This approach could ensure a more accurate prognosis and effective management of SLD, addressing both metabolic and alcohol-related factors.
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    Metabolic subtypes of patients with NAFLD exhibit distinctive cardiovascular risk profiles
    (2022) Martinez-Arranz, Ibon; Bruzzone, Chiara; Noureddin, Mazen; Gil-Redondo, Ruben; Minchole, Itziar; Bizkarguenaga, Maider; Arretxe, Enara; Iruarrizaga-Lejarreta, Marta; Fernandez-Ramos, David; Lopitz-Otsoa, Fernando; Mayo, Rebeca; Embade, Nieves; Newberry, Elizabeth; Mittendorf, Bettina; Izquierdo-Sanchez, Laura; Smid, Vaclav; Arnold, Jorge; Iruzubieta, Paula; Perez Castano, Ylenia; Krawczyk, Marcin; Marigorta, Urko M.; Morrison, Martine C.; Kleemann, Robert; Martin-Duce, Antonio; Hayardeny, Liat; Vitek, Libor; Bruha, Radan; Aller de la Fuente, Rocio; Crespo, Javier; Romero-Gomez, Manuel; Banales, Jesus M.; Arrese, Marco; Cusi, Kenneth; Bugianesi, Elisabetta; Klein, Samuel; Lu, Shelly C.; Anstee, Quentin M.; Millet, Oscar; Davidson, Nicholas O.; Alonso, Cristina; Mato, Jose M.
    Background and Aims We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. Approach and Results We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6, and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. Conclusions Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.
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    MetALD: New Perspectives on an Old Overlooked Disease
    (WILEY, 2025) Ayares, Gustavo; Díaz, Luis Antonio; Idalsoaga, Francisco; Alkhouri, Naim; Noureddin, Mazen; Bataller, Ramon; Loomba, Rohit; Arab, Juan Pablo; Arrese, Marco
    Metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-associated liver disease (ALD) are the major contributors to the liver disease burden globally. The rise in these conditions is linked to obesity, type 2 diabetes, metabolic syndrome and increased alcohol consumption. MASLD and ALD share risk factors, pathophysiology and histological features but differ in their thresholds for alcohol use, and the ALD definition does not require the presence of metabolic dysfunction. A recent multi-society consensus overhauled the nomenclature of liver steatosis and introduced the term MetALD to describe patients with metabolic dysfunction who drink more than those with MASLD and less than those with ALD. This new terminology aims to enhance the understanding and management of liver disease but poses challenges, such as the need to accurately measure alcohol consumption in research and clinical practice settings. Recent studies show that MetALD has significant implications for patient management, as it is associated with increased mortality risks and more severe liver outcomes compared to MASLD alone. MetALD patients face increased risks of liver disease progression, cancer and cardiovascular disease. The diagnosis of MetALD involves the adequate quantification of alcohol use through standardised questionnaires and/or biomarkers as well as proper assessment of liver disease stage and progression risk using non-invasive tools including serologic markers, imaging, elastography techniques and genetic testing. Effective management requires addressing both metabolic and alcohol-related factors to improve outcomes. This review intends to provide a comprehensive overview of MetALD, covering pathogenesis, potential diagnostic approaches, management strategies and emerging therapies.
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    Mineralocorticoid receptor modulation by dietary sodium influences NAFLD development in mice
    (ELSEVIER ESPANA, 2021) Cabrera, Daniel; Rao, Isabel; Raasch, Fabiola; Solis, Nancy; Pizarro, Margarita; Freire, Mariela; De Urturi, Diego Saenz; Ramirez, Carolina A.; Triantafilo, Nicolas; Leon, Jonathan; Riquelme, Arnoldo; Barrera, Francisco; Baudrand, Rene; Aspichueta, Patricia; Arrese, Marco; Arab, Juan P.
    Introduction and Objectives: Nonalcoholic-fatty-liver disease (NAFLD) is considered the hepatic manifestation of metabolic syndrome (MetS). Mineralocorticoid receptor (MR) activation is associated with increased risk of MetS but few studies have assessed the role of liver MR on NAFLD. We aimed to evaluate the effect of MR modulation by sodium intake in liver injury in experimental models of NAFLD.
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    Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: A case report with a long term follow-up
    (ELSEVIER ESPANA, 2011) Salech, Felipe; Valderrama, Sebastian; Nervi, Bruno; Carlos Rodriguez, Juan; Oksenberg, Danny; Koch, Alvaro; Smok, Gladys; Duarte, Ignacio; Maria Perez Ayuso, Rosa; Jarufe, Nicolas; Martinez, Jorge; Soza, Alejandro; Arrese, Marco; Riquelme, Arnoldo
    Hepatic epithelioid hemangioendothelioma (HEH) is an unusual, low-grade malignant vascular tumor of the liver. Here we describe a case of a 40-year-old woman who presented with abdominal pain in the upper right quadrant and giant hepatomegaly, in which imaging studies and a fine-needle liver biopsy confirmed the presence of a large EHE with an isolated lung metastasis. After balancing all possible therapeutic modalities the patient was treated conservatively with thalidomide (300 mg/day). The drug was well tolerated with minimal toxicity and the patient continues on therapy 109 months after treatment was started with no disease progression. Current therapeutic options for HEH are discussed in light of the clinical case with particular emphasis on anti-angiogenic therapies.
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    The impact of stigma on quality of life and liver disease burden among patients with nonalcoholic fatty liver disease
    (2024) Younossi, Zobair M.; AlQahtani, Saleh A.; Funuyet-Salas, Jesus; Romero-Gomez, Manuel; Yilmaz, Yusuf; Keklikkiran, Caglayan; Alswat, Khalid; Yu, Ming-Lung; Liu, Chun-Jen; Fan, Jian-Gao; Zheng, Ming-Hua; Burra, Patrizia; Francque, Sven M.; Castera, Laurent; Schattenberg, Joern M.; Newsome, Philip N.; Allen, Alina M.; El-Kassas, Mohamed; Treeprasertsuk, Sombat; Hameed, Saeed; Wong, Vincent Wai-Sun; Zelber-Sagi, Shira; Takahashi, Hirokazu; Kawaguchi, Takumi; Fernandez, Marlen I. Castellanos; Duseja, Ajay; Arrese, Marco; Rinella, Mary; Singal, Ashwani K.; Gordon, Stuart C.; Fuchs, Michael; Eskridge, Wayne; Alkhouri, Naim; Cusi, Kenneth; Loomba, Rohit; Ranagan, Jane; Kautz, Achim; Ong, Janus P.; Kugelmas, Marcelo; Eguchi, Yuichiro; Diago, Moises; Gerber, Lynn; Lam, Brian; Fornaresio, Lisa; Nader, Fatema; Spearman, C. Wendy; Roberts, Stuart K.; Chan, Wah-Kheong; Silva, Marcelo; Racila, Andrei; Golabi, Pegah; Ananchuensook, Prooksa; Henry, Linda; Stepanova, Maria; Carrieri, Patrizia; Lazarus, Jeffrey, V
    Background & Aims: Patients with nonalcoholic fatty liver disease (NAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) face a multifaceted disease burden which includes impaired health-related quality of life (HRQL) and potential stigmatization. We aimed to assess the burden of liver disease in patients with NAFLD and the relationship between experience of stigma and HRQL. Methods: Members of the Global NASH Council created a survey about disease burden in NAFLD. Participants completed a 35-item questionnaire to assess liver disease burden (LDB) (seven domains), the 36-item CLDQ-NASH (six domains) survey to assess HRQL and reported their experience with stigmatization and discrimination. Results: A total of 2,117 patients with NAFLD from 24 countries completed the LDB survey (48% Middle East and North Africa, 18% Europe, 16% USA, 18% Asia) and 778 competed CLDQ-NASH. Of the study group, 9% reported stigma due to NAFLD and 26% due to obesity. Participants who reported stigmatization due to NAFLD had substantially lower CLDQ-NASH scores (all p <0.0001). In multivariate analyses, experience with stigmatization or discrimination due to NAFLD was the strongest independent predictor of lower HRQL scores (beta from -5% to -8% of score range size, p <0.02). Experience with stigmatization due to obesity was associated with lower Activity, Emotional Health, Fatigue, and Worry domain scores, and being uncomfortable with the term "fatty liver disease" with lower Emotional Health scores (all p <0.05). In addition to stigma, the greatest disease burden as assessed by LDB was related to patients' self-blame for their liver disease. Conclusions: Stigmatization of patients with NAFLD, whether it is caused by obesity or NAFLD, is strongly and independently associated with a substantial impairment of their HRQL. Self-blame is an important part of disease burden among patients with NAFLD. Impact and implications: Patients with nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD), may experience impaired health-related quality of life and stigmatization. Using a specifically designed survey, we found that stigmatization of patients with NAFLD, whether it is caused by obesity or the liver disease per se, is strongly and independently associated with a substantial impairment of their quality of life. Physicians treating patients with NAFLD should be aware of the profound implications of stigma, the high prevalence of self-blame in the context of this disease burden, and that providers' perception may not adequately reflect patients' perspective and experience with the disease. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).