Browsing by Author "Ventura-Cots, Meritxell"

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    Identification of Optimal Therapeutic window for steroid use in severe alcohol associated Hepatitis: a worldwide study
    (2021) Arab, Juan Pablo; Díaz, Luis Antonio; Baeza, Natalia; Idalsoaga, Francisco; Fuentes-López, Eduardo; Arnold, Jorge; Ramírez, Carolina A.; Morales-Arraez, Dalia; Ventura-Cots, Meritxell; Alvarado-Tapias, Edilmar; Wei Zhang; Clark, Virginia; Simonetto, Douglas; Ahn, Joseph C.; Buryska, Seth; Mehta, Tej I.; Stefanescu, Horia; Horhat, Adelina; Bumbu, Andreea; Dunn, Winston
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    Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis
    (2021) Liu, Mengfei; Cao, Sheng; He, Li; Gao, Jinhang; Arab, Juan P.; Cui, Huarui; Xuan, Weixia; Gao, Yandong; Sehrawat, Tejasav S.; Hamdan, Feda H.; Ventura-Cots, Meritxell; Argemi, Josepmaria; Pomerantz, William C. K.; Johnsen, Steven A.; Lee, Jeong-Heon; Gao, Fei; Ordog, Tamas; Mathurin, Philippe; Revzin, Alexander; Bataller, Ramon; Yan, Huihuang; Shah, Vijay H.
    Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNF alpha with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNF alpha /NF-kappa B signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment. Alcoholic hepatitis is characterized by intense liver inflammation driven by excessive cytokines and chemokines production and immune cell infiltration. Here the authors identify a super-enhancer that regulates the expression of multiple CXCL chemokines in alcoholic hepatitis and may be a potential therapeutic target.
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    Trajectory of Serum Bilirubin Predicts Spontaneous Recovery in a Real-World Cohort of Patients With Alcoholic Hepatitis
    (2022) Parker, Richard; Cabezas, Joaquin; Altamirano, Jose; Arab, Juan Pablo; Ventura-Cots, Meritxell; Sinha, Ashish; Dhanda, Ashwin; Arrese, Marco; McCune, C. Anne; Rowe, Ian A.; Schnabl, Bernd; Mathurin, Phillipe; Shawcross, Debbie; Abraldes, Juan G.; Lucey, Michael R.; Garcia-Tsao, Guadalupe; Verna, Elizabeth; Brown, Robert S., Jr.; Bosques-Padilla, Francisco; Vargas, Victor; Louvet, Alexandre; Holt, Andrew P.; Bataller, Ramon
    BACKGROUND AND AIMS: Alcoholic hepatitis (AH) is a severe condition with poor short-term prognosis. Specific treatment with corticosteroids slightly improves short-term survival but is associated with infection and is not used in many centers. A reliable method to identify patients who will recover spontaneously will minimise the numbers of patients who experience side effects of available treatments.