Browsing by Author "Mathurin, Philippe"

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    Alcohol-Associated Liver Disease: Integrated Management With Alcohol Use Disorder
    (2023) Arab, Juan P.; Addolorato, Giovanni; Mathurin, Philippe; Thursz, Mark R.
    Alcohol-associated liver disease (ALD) is the most common cause of cirrhosis and liver-related mortality in many re-gions worldwide. Around 75% of patients with cirrhosis are unaware of their disease until they are referred to the emergency department. An innovative, noninvasive screening approach is required for an earlier diagnosis of liver fibrosis. In patients with ALD the physician is inevi-tably dealing with 2 major disorders: the liver disease it-self and the alcohol use disorder (AUD). Focus only on the liver disease will inevitably lead to failure because tran-sient improvements in liver function are rapidly over-turned if the patient returns to alcohol consumption. For this reason, integrated models of care provided by hep-atologists and addiction specialists are an effective approach, which are, however, not widely available. There are multiple pharmacologic and non-pharmacologic ther-apies for AUD. Progress has recently been made in the management of patients with severe AH who have improved survival through better understanding of the concept of response to medical treatment, improved sur-vival prediction, and the advent of early liver trans-plantation. The emerging concept is that listing for transplantation a patient with severe ALD could lead to adjusting the duration of abstinence according to the severity and evolution of liver dysfunction and the pa-tient's addictive profile.
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    Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
    (2019) Argemie, Josepmaria; Latasa, Maria U.; Atkinson, Stephen R.; Blokhin, Ilya O.; Massey, Verónica; Gue, Joel P.; Cabezas, Joaquín; Lozano, Juan J.; Van Booven, Derek; Arab Verdugo, Juan Pablo; Bell, Aaron; Cao, Sheng; Vernetti, Lawrence A.; Ventura Cots, Maritxell; Edmunds, Lia R.; Fondevilla, Constantino; Starkel, Peter; Dubuquoy, Laurent; Louvet, Alexandre; Odena, Gemma; Gómez, Juan L.; Aragón, Tomás; Altamirano, José; Caballeria, Juan; Jurczak, Michael J.; Taylor, D. Lansing; Berasain, Carmen; Wahlestedt, Claes; Monga, Satdaeshan P.; Morgan, Marsha Y.; Sancho Bru, Pau; Mathurin, Philippe; Furuya, Shinji; Lackner, Carolin; Rusyn, Ivan; Shah, Vijay H.; Thursz, Mark R.; Mann, Jelena; Ávila, Matías A.; Bataller, Ramón
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    Enhancer of Zeste Homologue 2 Inhibition Attenuates TGF-beta Dependent Hepatic Stellate Cell Activation and Liver Fibrosis
    (2019) Martin Mateos, Rosa; De Assuncao, Thiago M.; Arab Verdugo, Juan Pablo; Jalan Sakrikar, Nidhi; Yagoob, Usman; Greuter, Thomas; Verma, Vikas K.; Mathison, Angela J.; Cao, Sheng; Lomberk, Gwen; Mathurin, Philippe; Urrutia, Raúl; Huebert, Robert C.; Shah, Vijay H.
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    Global epidemiology of alcohol-related liver disease, liver cancer, and alcohol use disorder, 2000–2021
    (2025) Danpanichkul, Pojsakorn; Díaz Piga, Luis Antonio; Suparan, Kanokphong; Tothanarungroj, Primrose; Sirimangklanurak, Supapitch; Auttapracha, Thanida; Blaney, Hanna L.; Sukphutanan, Banthoon; Pang, Yanfang; Kongarin, Siwanart; Idalsoaga, Francisco; Fuentes-López, Eduardo; Leggio, Lorenzo; Noureddin, Mazen; White, Trenton M.; Louvet, Alexandre; Mathurin, Philippe; Loomba, Rohit; Kamath, Patrick S.; Rehm, Jürgen; Lazarus, Jeffrey V.; Wijarnpreecha, Karn; Arab Verdugo, Juan Pablo
    Background/Aims Alcohol represents a leading burden of disease worldwide, including alcohol use disorder (AUD) and alcohol-related liver disease (ALD). We aim to assess the global burden of AUD, ALD, and alcohol-attributable primary liver cancer between 2000–2021. Methods We registered the global and regional trends of AUD, ALD, and alcohol-related liver cancer using data from the Global Burden of Disease 2021 Study, the largest and most up-to-date global epidemiology database. We estimated the annual percent change (APC) and its 95% confidence interval (CI) to assess changes in age-standardized rates over time. Results In 2021, there were 111.12 million cases of AUD, 3.02 million cases of ALD, and 132,030 cases of alcohol-attributable primary liver cancer. Between 2000 and 2021, there was a 14.66% increase in AUD, a 38.68% increase in ALD, and a 94.12% increase in alcohol-attributable primary liver cancer prevalence. While the age-standardized prevalence rate for liver cancer from alcohol increased (APC 0.59%; 95% confidence interval [CI] 0.52 to 0.67%) over these years, it decreased for ALD (APC –0.71%; 95% CI –0.75 to –0.67%) and AUD (APC –0.90%; 95% CI –0.94 to –0.86%). There was significant variation by region, socioeconomic development level, and sex. During the last years (2019–2021), the prevalence, incidence, and death of ALD increased to a greater extent in females. Conclusions Given the high burden of AUD, ALD, and alcohol-attributable primary liver cancer, urgent measures are needed to prevent them at both global and national levels.
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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.