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1. TOPLINE RESULTS FROM A NEW ANALYSIS OF THE REGENERATE TRIAL OF OBETICHOLIC ACID FOR THE TREATMENT OF NONALCOHOLIC STEATOHEPATITIS

Author

Sanyal, Arun J, Loomba, Rohit, Anstee, Quentin M, Ratziu, Vlad, Kowdley, Kris V, Rinella, Mary E, Sheikh, Muhammad Y, Trotter, James F, Knapple, Whitfield L, Lawitz, Eric J, Abdelmalek, Manal F, Newsome, Philip N, Hansen, Bettina E, Mathurin, Philippe, Dufour, Jean-Francois, Berrey, M Michelle, Shiff, Steven J, Sawhney, Sangeeta, Capozza, Thomas, Leyva, Rina, Harrison, Stephen A, and Younossi, Zobair M

Subjects
Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology, Clinical sciences
Published
2023

2. Global epidemiology of alcohol-associated cirrhosis and HCC: trends, projections and risk factors

Author

Huang, Daniel Q, Mathurin, Philippe, Cortez-Pinto, Helena, and Loomba, Rohit

Subjects
Digestive Diseases, Substance Misuse, Genetics, Rare Diseases, Prevention, Chronic Liver Disease and Cirrhosis, Cancer, Liver Disease, Alcoholism, Alcohol Use and Health, Liver Cancer, 2.4 Surveillance and distribution, Aetiology, Stroke, Cardiovascular, Oral and gastrointestinal, Good Health and Well Being, Humans, Carcinoma, Hepatocellular, Liver Neoplasms, Diabetes Mellitus, Type 2, Risk Factors, Liver Cirrhosis, Alcoholic, Liver Cirrhosis, Ethanol, Incidence, Medical Biochemistry and Metabolomics, Clinical Sciences, Gastroenterology & Hepatology
Abstract

Heavy alcohol consumption is a major cause of morbidity and mortality. Globally, alcohol per-capita consumption rose from 5.5 litres in 2005 to 6.4 litres in 2016 and is projected to increase further to 7.6 litres in 2030. In 2019, an estimated 25% of global cirrhosis deaths were associated with alcohol. The global estimated age-standardized death rate (ASDR) of alcohol-associated cirrhosis was 4.5 per 100,000 population, with the highest and lowest ASDR in Africa and the Western Pacific, respectively. The annual incidence of hepatocellular carcinoma (HCC) among patients with alcohol-associated cirrhosis ranged from 0.9% to 5.6%. Alcohol was associated with approximately one-fifth of global HCC-related deaths in 2019. Between 2012 and 2017, the global estimated ASDR for alcohol-associated cirrhosis declined, but the ASDR for alcohol-associated liver cancer increased. Measures are required to curb heavy alcohol consumption to reduce the burden of alcohol-associated cirrhosis and HCC. Degree of alcohol intake, sex, older age, obesity, type 2 diabetes mellitus, gut microbial dysbiosis and genetic variants are key factors in the development of alcohol-associated cirrhosis and HCC. In this Review, we discuss the global epidemiology, projections and risk factors for alcohol-associated cirrhosis and HCC.

Published
2023

3. All‐cause and liver‐related mortality risk factors in excessive drinkers: Analysis of data from the UK biobank

Author

Whitfield, John B, Seth, Devanshi, Morgan, Timothy R, Aithal, Guruprasad P, Atkinson, Stephen R, Bataller, Ramon, Botwin, Gregory, Chalasani, Naga P, Cordell, Heather J, Daly, Ann K, Darlay, Rebecca, Day, Christopher P, Eyer, Florian, Foroud, Tatiana, Gleeson, Dermot, Goldman, David, Haber, Paul S, Jacquet, Jean‐Marc, Liang, Tiebing, Liangpunsakul, Suthat, Masson, Steven, Mathurin, Philippe, Moirand, Romain, Moreno, Christophe, Morgan, Marsha Y, Mueller, Sebastian, Müllhaupt, Beat, Nagy, Laura E, Nahon, Pierre, Nalpas, Bertrand, Naveau, Sylvie, Perney, Pascal, Pirmohamed, Munir, Schwantes‐An, Tae‐Hwi, Seitz, Helmut K, Soyka, Michael, Stickel, Felix, Thompson, Andrew, Thursz, Mark R, and Trepo, Eric

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Substance Misuse, Liver Disease, Nutrition, Brain Disorders, Alcoholism, Alcohol Use and Health, Clinical Research, Cancer, Oral and gastrointestinal, Good Health and Well Being, Humans, Male, Female, Alcoholism, Alcohol Drinking, Biological Specimen Banks, Risk Factors, Cardiovascular Diseases, Liver, United Kingdom, alcohol, alcohol dependence, all-cause mortality, excessive drinking, liver disease, GenomALC Consortium, Neurosciences, Psychology, Substance Abuse, Clinical sciences, Biological psychology, Clinical and health psychology
Abstract

BackgroundHigh alcohol intake is associated with increased mortality. We aimed to identify factors affecting mortality in people drinking extreme amounts of alcohol.MethodsWe obtained information from the UK Biobank on approximately 500,000 participants aged 40-70 years at baseline assessment in 2006-2010. Habitual alcohol intake, lifestyle and physiological data, laboratory test results, and hospital diagnoses and death certificate data (to June 2020) for 5136 men (2.20% of male participants) and 1504 women (0.60%) who reported consuming ≥80 or ≥50 g/day, respectively, were used in survival analysis.ResultsMortality hazard ratios for these excessive drinkers, compared to all other participants, were 2.02 (95% CI 1.89-2.17) for all causes, 1.89 (1.69-2.12) for any cancer, 1.87 (1.61-2.17) for any circulatory disease, and 9.40 (7.00-12.64) for any liver disease. Liver disease diagnosis or abnormal liver function tests predicted not only deaths attributed to liver disease but also those from cancers or circulatory diseases. Mortality among excessive drinkers was also associated with quantitative alcohol intake; diagnosed alcohol dependence, harmful use, or withdrawal syndrome; and current smoking at assessment.ConclusionsPeople with chronic excessive alcohol intake experience decreased average survival, but there is substantial variation in their mortality, with liver abnormality and alcohol dependence or other alcohol use disorders associated with a worse prognosis. Clinically, patients with these risk factors and high alcohol intake should be considered for early or intensive management. Research can usefully focus on the factors predisposing to dependence or liver abnormality.

Published
2022

4. Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort

Author

Raffi, François, Alric, Laurent, Miailhes, Patrick, Tran, Albert, Stern, Christiane, Causse, Xavier, Tripon, Simona, Riachi, Ghassan, Chazouillères, Olivier, Abergel, Armando, d’Alteroche, Louis, Gournay, Jérôme, Lagadic, Garance, Carrieri, Patrizia, Brichler, Ségolène, Siguier, Martin, Krause, Jessica, Foucher, Juliette, Ben Ali, Souad, Meszaros, Magdalena, Varaut, Anne, Canva, Valérie, de Lédinghen, Victor, Fougerou-Leurent, Claire, Le Pabic, Estelle, Pol, Stanislas, Alfaiate, Dulce, Lacombe, Karine, Hilleret, Marie-Noëlle, Lascoux-Combe, Caroline, Minello, Anne, Billaud, Eric, Rosa, Isabelle, Gervais, Anne, Ratziu, Vlad, Ganne, Nathalie, Pageaux, Georges-Philippe, Leroy, Vincent, Loustaud-Ratti, Véronique, Mathurin, Philippe, Chas, Julie, Jezequel, Caroline, Métivier, Sophie, Dumortier, Jérôme, Arpurt, Jean-Pierre, Asselah, Tarik, Roche, Bruno, Le Gruyer, Antonia, Valantin, Marc-Antoine, Scholtès, Caroline, Gordien, Emmanuel, Tual, Christelle, Kortebi, Amel, Coulibaly, Fatoumata, Rosenthal, Eric, Subic-Levrero, Miroslava, Roulot, Dominique, and Zoulim, Fabien

Published
2024
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5. Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide

Author

El Messaoudi, Selma, Brichler, Ségolène, Fougerou-Leurent, Claire, Gordien, Emmanuel, Gerber, Athenaïs, Kortebi, Amal, Lagadic, Garance, Subic-Levrero, Miroslava, Metivier, Sophie, Pol, Stanislas, Minello, Anne, Ratziu, Vlad, Leroy, Vincent, Mathurin, Philippe, Alric, Laurent, Coulibaly, Fatoumata, Pawlotsky, Jean-Michel, Zoulim, Fabien, de Lédinghen, Victor, and Guedj, Jérémie

Published
2024
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6. Author Correction: Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis

Author

Argemi, Josepmaria, Latasa, Maria U., Atkinson, Stephen R., Blokhin, Ilya O., Massey, Veronica, Gue, Joel P., Cabezas, Joaquin, Lozano, Juan J., Van Booven, Derek, Bell, Aaron, Cao, Sheng, Vernetti, Lawrence A., Arab, Juan P., Ventura-Cots, Meritxell, Edmunds, Lia R., Fondevila, Constantino, Stärkel, Peter, Dubuquoy, Laurent, Louvet, Alexandre, Odena, Gemma, Gomez, Juan L., Aragon, Tomas, Altamirano, Jose, Caballeria, Juan, Jurczak, Michael J., Taylor, D. Lansing, Berasain, Carmen, Wahlestedt, Claes, Monga, Satdarshan P., Morgan, Marsha Y., Sancho-Bru, Pau, Mathurin, Philippe, Furuya, Shinji, Lackner, Carolin, Rusyn, Ivan, Shah, Vijay H., Thursz, Mark R., Mann, Jelena, Avila, Matias A., and Bataller, Ramon

Published
2023
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7. A genetic risk score and diabetes predict development of alcohol-related cirrhosis in drinkers

Author

Whitfield, John B, Schwantes-An, Tae-Hwi, Darlay, Rebecca, Aithal, Guruprasad P, Atkinson, Stephen R, Bataller, Ramon, Botwin, Greg, Chalasani, Naga P, Cordell, Heather J, Daly, Ann K, Day, Christopher P, Eyer, Florian, Foroud, Tatiana, Gleeson, Dermot, Goldman, David, Haber, Paul S, Jacquet, Jean-Marc, Liang, Tiebing, Liangpunsakul, Suthat, Masson, Steven, Mathurin, Philippe, Moirand, Romain, McQuillin, Andrew, Moreno, Christophe, Morgan, Marsha Y, Mueller, Sebastian, Müllhaupt, Beat, Nagy, Laura E, Nahon, Pierre, Nalpas, Bertrand, Naveau, Sylvie, Perney, Pascal, Pirmohamed, Munir, Seitz, Helmut K, Soyka, Michael, Stickel, Felix, Thompson, Andrew, Thursz, Mark R, Trépo, Eric, Morgan, Timothy R, Seth, Devanshi, and Consortium, GenomALC

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Rare Diseases, Liver Cancer, Genetics, Liver Disease, Clinical Research, Substance Misuse, Genetic Testing, Cancer, Alcoholism, Alcohol Use and Health, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Metabolic and endocrine, Oral and gastrointestinal, Good Health and Well Being, Adult, Alcohol Drinking, Case-Control Studies, Cohort Studies, Diabetes Mellitus, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Liver Cirrhosis, Alcoholic, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Assessment, Hepatocellular carcinoma, risk stratification, chronic alcohol use, genome-wide association, single nucleotide polymorphism, coffee, GenomALC Consortium, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background & aimsOnly a minority of excess alcohol drinkers develop cirrhosis. We developed and evaluated risk stratification scores to identify those at highest risk.MethodsThree cohorts (GenomALC-1: n = 1,690, GenomALC-2: n = 3,037, UK Biobank: relevant n = 6,898) with a history of heavy alcohol consumption (≥80 g/day (men), ≥50 g/day (women), for ≥10 years) were included. Cases were participants with alcohol-related cirrhosis. Controls had a history of similar alcohol consumption but no evidence of liver disease. Risk scores were computed from up to 8 genetic loci identified previously as associated with alcohol-related cirrhosis and 3 clinical risk factors. Score performance for the stratification of alcohol-related cirrhosis risk was assessed and compared across the alcohol-related liver disease spectrum, including hepatocellular carcinoma (HCC).ResultsA combination of 3 single nucleotide polymorphisms (SNPs) (PNPLA3:rs738409, SUGP1-TM6SF2:rs10401969, HSD17B13:rs6834314) and diabetes status best discriminated cirrhosis risk. The odds ratios (ORs) and (95% CIs) between the lowest (Q1) and highest (Q5) score quintiles of the 3-SNP score, based on independent allelic effect size estimates, were 5.99 (4.18-8.60) (GenomALC-1), 2.81 (2.03-3.89) (GenomALC-2), and 3.10 (2.32-4.14) (UK Biobank). Patients with diabetes and high risk scores had ORs of 14.7 (7.69-28.1) (GenomALC-1) and 17.1 (11.3-25.7) (UK Biobank) compared to those without diabetes and with low risk scores. Patients with cirrhosis and HCC had significantly higher mean risk scores than patients with cirrhosis alone (0.76 ± 0.06 vs. 0.61 ± 0.02, p = 0.007). Score performance was not significantly enhanced by information on additional genetic risk variants, body mass index or coffee consumption.ConclusionsA risk score based on 3 genetic risk variants and diabetes status enables the stratification of heavy drinkers based on their risk of cirrhosis, allowing for the provision of earlier preventative interventions.Lay summaryExcessive chronic drinking leads to cirrhosis in some people, but so far there is no way to identify those at high risk of developing this debilitating disease. We developed a genetic risk score that can identify patients at high risk. The risk of cirrhosis is increased >10-fold with just two risk factors - diabetes and a high genetic risk score. Risk assessment using this test could enable the early and personalised management of this disease in high-risk patients.

Published
2022

8. Long-term outcome following liver transplantation of patients with ACLF grade 3

Author

Artru, Florent, Sacleux, Sophie-Caroline, Ursic-Bedoya, Jose, Ntandja Wandji, Line Carole, Lutu, Alina, L’Hermite, Sebastien, Levy, Clementine, Khaldi, Marion, Levesque, Eric, Dharancy, Sebastien, Boleslawski, Emmanuel, Lebuffe, Gilles, Le Goffic, Charles, Ichai, Philippe, Coilly, Audrey, De Martin, Eleonora, Vibert, Eric, Meszaros, Magdalena, Herrerro, Astrid, Monet, Clement, Jaber, Samir, Samuel, Didier, Mathurin, Philippe, Labreuche, Julien, Pageaux, Georges-Philippe, Saliba, Faouzi, and Louvet, Alexandre

Published
2024
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9. Time-of-day-dependent variation of the human liver transcriptome and metabolome is disrupted in MASLD

Author

Johanns, Manuel, Haas, Joel T., Raverdy, Violetta, Vandel, Jimmy, Chevalier-Dubois, Julie, Guille, Loic, Derudas, Bruno, Legendre, Benjamin, Caiazzo, Robert, Verkindt, Helene, Gnemmi, Viviane, Leteurtre, Emmanuelle, Derhourhi, Mehdi, Bonnefond, Amélie, Froguel, Philippe, Eeckhoute, Jérôme, Lassailly, Guillaume, Mathurin, Philippe, Pattou, François, Staels, Bart, and Lefebvre, Philippe

Published
2024
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10. Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis

Author

Sanyal, Arun J., Ratziu, Vlad, Loomba, Rohit, Anstee, Quentin M., Kowdley, Kris V., Rinella, Mary E., Sheikh, Muhammad Y., Trotter, James F., Knapple, Whitfield, Lawitz, Eric J., Abdelmalek, Manal F., Newsome, Philip N., Boursier, Jérôme, Mathurin, Philippe, Dufour, Jean-François, Berrey, M. Michelle, Shiff, Steven J., Sawhney, Sangeeta, Capozza, Thomas, Leyva, Rina, Harrison, Stephen A., and Younossi, Zobair M.

Published
2023
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11. Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming

Author

Aguilar-Bravo, Beatriz, Ariño, Silvia, Blaya, Delia, Pose, Elisa, Martinez García de la Torre, Raquel A., Latasa, María U., Martínez-Sánchez, Celia, Zanatto, Laura, Sererols-Viñas, Laura, Cantallops-Vilà, Paula, Affo, Silvia, Coll, Mar, Thillen, Xavier, Dubuquoy, Laurent, Avila, Matías A., Argemi, Josepmaria, Paz, Arantza Lamas, Nevzorova, Yulia A., Cubero, Francisco Javier, Bataller, Ramon, Lozano, Juan José, Ginès, Pere, Mathurin, Philippe, and Sancho-Bru, Pau

Published
2023
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13. Intestinal Virome in Patients With Alcoholic Hepatitis

Author

Jiang, Lu, Lang, Sonja, Duan, Yi, Zhang, Xinlian, Gao, Bei, Chopyk, Jessica, Schwanemann, Leila K, Ventura‐Cots, Meritxell, Bataller, Ramon, Bosques‐Padilla, Francisco, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie L, Ho, Samuel B, Louvet, Alexandre, Lucey, Michael R, Mathurin, Philippe, Garcia‐Tsao, Guadalupe, Kisseleva, Tatiana, Brenner, David A, Tu, Xin M, Stärkel, Peter, Pride, David, Fouts, Derrick E, and Schnabl, Bernd

Subjects
Clinical Research, Hepatitis, Substance Misuse, Alcoholism, Alcohol Use and Health, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Disease, Infection, Oral and gastrointestinal, Good Health and Well Being, Adult, Aged, Animals, Bacteriophages, Case-Control Studies, DNA, Viral, End Stage Liver Disease, Feces, Female, Hepatitis, Alcoholic, Herpesviridae, Humans, Intestinal Mucosa, Liver, Liver Cirrhosis, Male, Metagenomics, Middle Aged, Parvoviridae, RNA, Viral, Severity of Illness Index, Survival Rate, Virome, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Background and aimsAlcoholic hepatitis (AH) is a severe manifestation of alcohol-associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.Approach and resultsWe extracted virus-like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus-like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia-, Enterobacteria-, and Enterococcus phages were over-represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End-Stage Liver Disease score, and associated with increased 90-day mortality.ConclusionsIn conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.

Published
2020

16. TACE and conformal radiotherapy vs. TACE alone for hepatocellular carcinoma: A randomised controlled trial

Author

Féray, Cyrille, Campion, Loic, Mathurin, Philippe, Archambreaud, Isabelle, Mirabel, Xavier, Bronowicki, Jean Pierre, Rio, Emmanuel, Perret, Christophe, Mineur, Laurent, Oberti, Frédéric, Touchefeu, Yann, Gournay, Jérôme, Regnault, Hélène, Edeline, Julien, Rode, Agnès, Hillion, Patrick, Blanc, Jean Frédéric, Khac, Eric Nguyen, Azoulay, Daniel, Luciani, Alain, Preglisasco, Athena Galetto, Faurel-Paul, Elodie, Auble, Hélène, Mornex, Françoise, and Merle, Philippe

Published
2023
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18. Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease.

Author

Duan, Yi, Llorente, Cristina, Lang, Sonja, Brandl, Katharina, Chu, Huikuan, Jiang, Lu, White, Richard C, Clarke, Thomas H, Nguyen, Kevin, Torralba, Manolito, Shao, Yan, Liu, Jinyuan, Hernandez-Morales, Adriana, Lessor, Lauren, Rahman, Imran R, Miyamoto, Yukiko, Ly, Melissa, Gao, Bei, Sun, Weizhong, Kiesel, Roman, Hutmacher, Felix, Lee, Suhan, Ventura-Cots, Meritxell, Bosques-Padilla, Francisco, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie L, Ho, Samuel B, Louvet, Alexandre, Lucey, Michael R, Mathurin, Philippe, Garcia-Tsao, Guadalupe, Bataller, Ramon, Tu, Xin M, Eckmann, Lars, van der Donk, Wilfred A, Young, Ry, Lawley, Trevor D, Stärkel, Peter, Pride, David, Fouts, Derrick E, and Schnabl, Bernd

Subjects
Liver, Hepatocytes, Feces, Animals, Mice, Inbred C57BL, Humans, Mice, Enterococcus faecalis, Bacteriophages, Fatty Liver, Hepatitis, Alcoholic, Alcoholism, Ethanol, Germ-Free Life, Female, Male, Perforin, Gastrointestinal Microbiome, Phage Therapy, Alcoholism, Alcohol Use and Health, Clinical Research, Liver Disease, Substance Abuse, Chronic Liver Disease and Cirrhosis, Hepatitis, Infectious Diseases, Digestive Diseases, 2.1 Biological and endogenous factors, Oral and gastrointestinal, General Science & Technology
Abstract

Chronic liver disease due to alcohol-use disorder contributes markedly to the global burden of disease and mortality1-3. Alcoholic hepatitis is a severe and life-threatening form of alcohol-associated liver disease. The gut microbiota promotes ethanol-induced liver disease in mice4, but little is known about the microbial factors that are responsible for this process. Here we identify cytolysin-a two-subunit exotoxin that is secreted by Enterococcus faecalis5,6-as a cause of hepatocyte death and liver injury. Compared with non-alcoholic individuals or patients with alcohol-use disorder, patients with alcoholic hepatitis have increased faecal numbers of E. faecalis. The presence of cytolysin-positive (cytolytic) E. faecalis correlated with the severity of liver disease and with mortality in patients with alcoholic hepatitis. Using humanized mice that were colonized with bacteria from the faeces of patients with alcoholic hepatitis, we investigated the therapeutic effects of bacteriophages that target cytolytic E. faecalis. We found that these bacteriophages decrease cytolysin in the liver and abolish ethanol-induced liver disease in humanized mice. Our findings link cytolytic E. faecalis with more severe clinical outcomes and increased mortality in patients with alcoholic hepatitis. We show that bacteriophages can specifically target cytolytic E. faecalis, which provides a method for precisely editing the intestinal microbiota. A clinical trial with a larger cohort is required to validate the relevance of our findings in humans, and to test whether this therapeutic approach is effective for patients with alcoholic hepatitis.

Published
2019

19. Integrating genetic variants into clinical models for hepatocellular carcinoma risk stratification in cirrhosis

Author

Nahon, Pierre, Asselah, Tarik, Guyader, Dominique, Pol, Stanislas, Fontaine, Hélène, Pageaux, Georges-Philippe, De Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Roulot, Dominique, Tran, Albert, Bronowicki, Jean-Pierre, Decaensi, Thomas, Riachi, Ghassan, Calès, Paul, Péron, Jean-Marie, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Dharancy, Sebastien, Blanc, Jean-Frédéric, Abergel, Armand, Chazouillères, Olivier, Mallat, Ariane, Grangé, Jean-Didier, Attali, Pierre, Louis d’Alteroche, Wartelle, Claire, Dao, Thông, Thabut, Dominique, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Nguyen-Khac, Eric, Bernard-Chabert, Brigitte, Hillaire, Sophie, Di Martino, Vincent, Ganne-Carrié, Nathalie, Chaffaut, Cendrine, Archambeaud, Isabelle, d’Alteroche, Louis, Oberti, Frédéric, Moreno, Christophe, Louvet, Alexandre, Moirand, Romain, Goria, Odile, Carbonell, Nicolas, Duclos-Vallée, Jean-Charles, de Ledinghen, Victor, Ozenne, Violaine, Henrion, Jean, Perlemuter, Gabriel, Amiot, Xavier, Zarski, Jean-Pierre, Chevret, Sylvie, Bamba-Funck, Jessica, Layese, Richard, Trépo, Eric, Zucman-Rossi, Jessica, Cagnot, Carole, Guyot, Erwan, Ziol, Marianne, Sutton, Angela, and Audureau, Etienne

Published
2023
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21. SAT-439-YI Socioeconomic deprivation is independently associated with hepatocellular carcinoma mortality in a western european country with single-payer healthcare

Author

Ningarhari, Massih, primary, Lacour, Alexandre, additional, Dauchy, Simon, additional, Genin, Michael, additional, Bruandet, Amelie, additional, Cattan, Stéphane, additional, Wandji, Line Carolle Ntandja, additional, Lemaître, Elise, additional, Canva, Valérie, additional, Louvet, Alexandre, additional, Mathurin, Philippe, additional, Dharancy, Sébastien, additional, and Lassailly, Guillaume, additional

Published
2024
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22. GS-010 Early liver transplantation for severe alcohol-related hepatitis: long-term data of the french-belgian controlled study (QuickTrans)

Author

Louvet, Alexandre, primary, Favier, Laurie, additional, Labreuche, Julien, additional, Moreno, Christophe, additional, Vanlemmens, Claire, additional, Moirand, Romain, additional, Wandji, Line Carolle Ntandja, additional, Feray, Cyrille, additional, Dumortier, Jérôme, additional, Pageaux, Georges-Philippe, additional, Bureau, Christophe, additional, Chermak, Faiza, additional, Duvoux, Christophe, additional, Thabut, Dominique, additional, Hilleret, Marie-Noëlle, additional, Carbonell, Nicolas, additional, Salamé, Ephrem, additional, Anty, Rodolphe, additional, Gournay, Jérôme, additional, Delwaide, Jean, additional, Silvain, Christine, additional, Lassailly, Guillaume, additional, Dharancy, Sébastien, additional, Khac, Eric Nguyen, additional, Samuel, Didier, additional, Duhamel, Alain, additional, and Mathurin, Philippe, additional

Published
2024
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23. OS-060 Hepatocellular carcinoma development despite histological regression of liver fibrosis following HCV cure (ANRS CirVir, Hepather, LICAVIR)

Author

Nahon, Pierre, primary, lusivka-Nzinga, Clovis, additional, Merle, Philippe, additional, Zoulim, Fabien, additional, Decaens, Thomas, additional, Ganne-Carrié, Nathalie, additional, Pageaux, Georges-Philippe, additional, Leroy, Vincent, additional, Alric, Laurent, additional, Bronowicki, Jean-Pierre, additional, Bourliere, Marc, additional, Gournay, Jérôme, additional, Tran, Albert, additional, Pol, Stanislas, additional, Mathurin, Philippe, additional, Loustaud-Ratti, Veronique, additional, Metivier, Sophie, additional, de Lédinghen, Victor, additional, Abergel, Armand, additional, Thabut, Dominique, additional, Dalteroche, Louis, additional, Bouattour, Mohamed, additional, Asselah, Tarik, additional, Ouzan, Denis, additional, Cales, Paul, additional, Chazouillères, Olivier, additional, Gelu-Simeon, Moana, additional, Roulot, Dominique, additional, Boursier, Jerome, additional, Carole, Cagnot, additional, Tamazirt, Sonia, additional, Pascale, Alina, additional, Nilusmas, Samuel, additional, Lewin, Maite, additional, Ziol, Marianne, additional, Carrat, Fabrice, additional, and Duclos-Vallée, Jean-Charles, additional

Published
2024
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24. OS-034 Safety and efficacy of REP 2139-Mg in hepatitis D patients with advanced liver disease: an international compassionate use program

Author

Stern, Christiane, primary, Bourliere, Marc, additional, Loustaud-Ratti, Veronique, additional, Bardou-Jacquet, Edouard, additional, Alric, Laurent, additional, Colombain, Lea, additional, Meszaros, Magdalena, additional, Metivier, Sophie, additional, Mathurin, Philippe, additional, Yurdaydin, Cihan, additional, Jachs, Mathias, additional, Reiberger, Thomas, additional, Brancaccio, Giuseppina, additional, Yardeni, David, additional, Etzion, Ohad, additional, Neumann-Haefelin, Christoph, additional, Douglas, Mark, additional, Poulin, Sebastien, additional, Benali, Souad, additional, Bedoya, José Ursic, additional, Metin, Olga, additional, Bazinet, Michel, additional, Schwarz, Michael, additional, Gaeta, Giovanni Battista, additional, Vitale, Alessandro, additional, Svicher, Valentina, additional, Cillo, Umberto, additional, Brichler, Segolene, additional, Gordien, Emmanuel, additional, Chevaliez, Stéphane, additional, and Vaillant, Andrew, additional

Published
2024
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27. Increased hepatic PDGF-AA signaling mediates liver insulin resistance in obesity associated type 2 diabetes

Author

Abderrahmani, Amar, Yengo, Loic, Caiazzo, Robert, Canouil, Mickael, Cauchi, Stephane, Raverdy, Violeta, Plaisance, Valerie, Pawlowski, Valerie, Lobbens, Stephane, Maillet, Julie, Rolland, Laure, Boutry, Raphael, Queniat, Gurvan, Kwapich, Maxime, Tenenbaum, Mathie, Bricambert, Julien, Saussenthaler, Sophie, Anthony, Elodie, Jha, Pooja, Derop, Julien, Sand, Olivier, Rabearivelo, Iandry, Leloire, Audrey, Pigeyre, Marie, Daujat-Chavanieu, Martine, Gerbal-Chaloin, Sabine, Dayeh, Tasnim, Lassailly, Guillaume, Mathurin, Philippe, Staels, Bart, Auwerx, Johan, Schurmann, Annette, Postic, Catherine, Schafmayer, Clemens, Hampe, Jochen, Bonnefond, Amelie, Pattou, Francois, and Froguel, Philippe

Subjects
Quantitative Biology - Cell Behavior
Abstract

Type 2 diabetes (T2D) is closely linked with non-alcoholic fatty liver disease (NAFLD) and hepatic insulin resistance, but the involved mechanisms are still elusive. Using DNA methylome and transcriptome analyses of livers from obese individuals, we found that both hypomethylation at a CpG site in PDGFA (encoding platelet derived growth factor alpha) and PDGFA overexpression are associated with increased T2D risk, hyperinsulinemia, increased insulin resistance and increased steatohepatitis risk. Both genetic risk score studies and human cell modeling pointed to a causative impact of high insulin levels on PDGFA CpG site hypomethylation, PDGFA overexpression, and increased PDGF-AA secretion from liver. We found that PDGF-AA secretion further stimulates its own expression through protein kinase C activity and contributes to insulin resistance through decreased expression of both insulin receptor substrate 1 and of insulin receptor. Importantly, hepatocyte insulin sensitivity can be restored by PDGF-AA blocking antibodies, PDGF receptor inhibitors and by metformin opening therapeutic avenues. Conclusion: Therefore, in the liver of obese patients with T2D, the increased PDGF-AA signaling contributes to insulin resistance, opening new therapeutic avenues against T2D and NAFLD., Comment: 29 pages 7 figures 1 tables

Published
2017

28. The diagnostic performance of a simplified blood test (SteatoTest-2) for the prediction of liver steatosis

Author

Poynard, Thierry, Peta, Valentina, Munteanu, Mona, Charlotte, Frederic, Ngo, Yen, Ngo, An, Perazzo, Hugo, Deckmyn, Olivier, Pais, Raluca, Mathurin, Philippe, Myers, Rob, Loomba, Rohit, and Ratziu, Vlad

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Chronic Liver Disease and Cirrhosis, Clinical Research, Liver Disease, Digestive Diseases, Adult, Age Factors, Biomarkers, Biopsy, Fatty Liver, Feasibility Studies, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prevalence, Reproducibility of Results, Retrospective Studies, Severity of Illness Index, Sex Factors, control group for steatosis test, false-negative steatosis test, false-positive steatosis test, noninvasive diagnosis, SteatoTest, FLIP consortium, the FibroFrance-CPAM group, the FibroFrance-Obese group, and the Selonsertib group, Gastroenterology & Hepatology, Clinical sciences
Abstract

BackgroundSerum biomarkers of steatosis such as the SteatoTest are recommended for large-scale screening studies, because imaging is less accessible and more expensive.AimsThe primary aim of this retrospective analysis of prospective studies was to construct a new SteatoTest-2 that was not inferior to the reference first-generation SteatoTest, but that did not include BMI or bilirubin, as these two components can increase test variability because of the assessment of weight and height and in case of Gilbert syndrome or hemolysis, respectively.Patients and methodsFive different subsets of 2997 patients with biopsies were evaluated for test construction and validation, and four to assess the prevalence of steatosis in target populations with increasing risks of steatosis. The performance of the SteatoTest-2 was compared with the reference test, using the noninferiority test (0.10 margin) and the Lin concordance coefficient.ResultsAreas under the receiver operating characteristic curve of the SteatoTest-2 were noninferior to the reference test (P

Published
2019

29. Early liver transplantation for severe alcohol-related hepatitis not responding to medical treatment: a prospective controlled study

Author

Berthot, Christophe, Claudet, Sylvie, Doussot, Alexandre, Gérardin, Caroline, Muel, Emilie, Hiriart, Jean-Baptiste, Degré, Delphine, Gustot, Thierry, Bonadona, Agnès, Bordy, Laure, Hilleret, Marie-Noelle, Detry, Olivier, Honoré, Pierre, Meurisse, Nicolas, Boleslawski, Emmanuel, Deplanque, Dominique, El Amrani, Mehdi, Lebuffe, Gilles, Millet, Guillaume, Soret, Daphnée, Truant, Stéphanie, Erard-Poinsot, Domitille, Radenne, Sylvie, Faure, Stéphanie, Gelsi, Eve, Truchi, Régine, Rudler, Marika, Rouleau, Laëtitia, Brenner, Audrey, Larrue, Hélène, Péron, Jean-Marie, Robic, Marie-Angèle, Antonini, Teresa, Duclos-Vallée, Jean-Charles, Louvet, Alexandre, Labreuche, Julien, Moreno, Christophe, Vanlemmens, Claire, Moirand, Romain, Féray, Cyrille, Dumortier, Jérôme, Pageaux, Georges-Philippe, Bureau, Christophe, Chermak, Faïza, Duvoux, Christophe, Thabut, Dominique, Leroy, Vincent, Carbonell, Nicolas, Rolland, Benjamin, Salamé, Ephrem, Anty, Rodolphe, Gournay, Jérôme, Delwaide, Jean, Silvain, Christine, Lucidi, Valerio, Lassailly, Guillaume, Dharancy, Sébastien, Nguyen-Khac, Eric, Samuel, Didier, Duhamel, Alain, and Mathurin, Philippe

Published
2022
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31. Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis

Author

Bobowski-Gerard, Marie, Boulet, Clémence, Zummo, Francesco P., Dubois-Chevalier, Julie, Gheeraert, Céline, Bou Saleh, Mohamed, Strub, Jean-Marc, Farce, Amaury, Ploton, Maheul, Guille, Loïc, Vandel, Jimmy, Bongiovanni, Antonino, Very, Ninon, Woitrain, Eloïse, Deprince, Audrey, Lalloyer, Fanny, Bauge, Eric, Ferri, Lise, Ntandja-Wandji, Line-Carolle, Cotte, Alexia K., Grangette, Corinne, Vallez, Emmanuelle, Cianférani, Sarah, Raverdy, Violeta, Caiazzo, Robert, Gnemmi, Viviane, Leteurtre, Emmanuelle, Pourcet, Benoit, Paumelle, Réjane, Ravnskjaer, Kim, Lassailly, Guillaume, Haas, Joel T., Mathurin, Philippe, Pattou, François, Dubuquoy, Laurent, Staels, Bart, Lefebvre, Philippe, and Eeckhoute, Jérôme

Published
2022
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32. Clinical outcomes after treatment with direct antiviral agents: beyond the virological response in patients with previous HCV-related decompensated cirrhosis

Author

Pageaux, Georges-Philippe, Nzinga, Clovis Lusivika, Ganne, Nathalie, Samuel, Didier, Dorival, Céline, Zoulim, Fabien, Cagnot, Carole, Decaens, Thomas, Thabut, Dominique, Asselah, Tarik, Mathurin, Philippe, Habersetzer, François, Bronowicki, Jean-Pierre, Guyader, Dominique, Rosa, Isabelle, Leroy, Vincent, Chazouilleres, Olivier, de Ledinghen, Victor, Bourliere, Marc, Causse, Xavier, Cales, Paul, Metivier, Sophie, Loustaud-Ratti, Véronique, Riachi, Ghassan, Alric, Laurent, Gelu-Simeon, Moana, Minello, Anne, Gournay, Jérôme, Geist, Claire, Tran, Albert, Abergel, Armand, Portal, Isabelle, d’Alteroche, Louis, Raffi, François, Fontaine, Hélène, Carrat, Fabrice, and Pol, Stanislas

Published
2022
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33. Cannabis use as a factor of lower corpulence in hepatitis C-infected patients: results from the ANRS CO22 Hepather cohort

Author

Barré, Tangui, Carrat, Fabrice, Ramier, Clémence, Fontaine, Hélène, Di Beo, Vincent, Bureau, Morgane, Dorival, Céline, Larrey, Dominique, Delarocque-Astagneau, Elisabeth, Mathurin, Philippe, Marcellin, Fabienne, Petrov-Sanchez, Ventzislava, Cagnot, Carole, Carrieri, Patrizia, Pol, Stanislas, and Protopopescu, Camelia

Published
2022
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35. Early hepatocellular carcinoma detection using magnetic resonance imaging is cost-effective in high-risk patients with cirrhosis

Author

Nahon, Pierre, Asselah, Tarik, Guyader, Dominique, Pol, Stanislas, Fontaine, Hélène, Pageaux, Georges-Philippe, De Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Roulot, Dominique, Tran, Albert, Bronowicki, Jean-Pierre, Decaensi, Thomas, Riachi, Ghassan, Calès, Paul, Péron, Jean-Marie, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Dharancy, Sebastien, Blanc, Jean-Frédéric, Abergel, Armand, Chazouillères, Olivier, Mallat, Ariane, Grangé, Jean-Didier, Attali, Pierre, d’Alteroche, Louis, Wartelle, Claire, Dao, Thông, Thabut, Dominique, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Nguyen-Khac, Eric, Bernard-Chabert, Brigitte, Hillaire, Sophie, Di Martino, Vincent, Bonnet, Delphine, Payssan-Sicart, Virginie, Pomes, Chloe, Bailly, François, Beaudoin, Marjolaine, Giboz, Dominique, Hartig-Lavie, Kerstin, Maynard, Marianne, Billaud, Eric, Boutoille, David, Cavellec, Morane, Cheraud-Carpentier, Marjorie, Hubert, Isabelle, Benhida, Jaouad, Lannes, Adrien, Lunel, Françoise, Oberti, Frédéric, Boyer, Nathalie, Giuily, Nathalie, Castelnau, Corinne, Scoazec, Giovanna, Chibah, Aziza, Keser, Sylvie, Bonardi, Karim, Vallet-Pichard, Anaïs, Sogni, Philippe, Foucher, Juliette, Hiriart, Jean-Baptiste, Wilson, Amy, Shili, Sarah, Chermak, Faiza, Ansaldi, Christelle, Ben Amara, Nisserine, Chouquet, Laëtitia, De Luca, Emilie, Oules, Valérie, Anty, Rodolphe, Gelsi, Eve, Truchi, Régine, Luckina, Elena, Messaoudi, Nadia, Moussali, Joseph, De Dieuleveult, Barbara, Labarriere, Damien, Poter, Pascal, Si Ahmed, Si Nafa, Grando-Lemaire, Véronique, Bourcier, Valérie, Brulé, Séverine, Stalhberger, Thomas, Jezequel, Caroline, Brener, Audrey, Laligant, Anne, Rabot, Aline, Renard, Isabelle, Baumert, Thomas F., Dofföel, Michel, Mutter, Catherine, Simo-Noumbissie, Pauline, Razi, Esma, Barraud, Hélène, Bensenane, Mouni, Nani, Abdelbasset, Hassani-Nani, Sarah, Bernard, Marie-Albertine, Bismuth, Michael, Caillo, Ludovic, Faure, Stéphanie, Ripault, Marie Pierre, Bureau, Christophe, Peron, Jean Marie, Robic, Marie Angèle, Tarallo, Léa, Faure, Marine, Froissart, Bruno, Hilleret, Marie-Noelle, Zarski, Jean-Pierre, Goria, Odile, Grard, Victorien, Montialoux, Hélène, François, Muriel, Ouedraogo, Christian, Pauleau, Christelle, Varault, Anne, Andreani, Tony, Angoulevant, Bénédicte, Chevance, Azeline, Serfaty, Lawrence, Antonini, Teresa, Coilly, Audrey, Duclos Vallée, Jean-Charles, Tateo, Mariagrazia, Bonny, Corinne, Brigitte, Chanteranne, Lamblin, Géraldine, Muti, Léon, Babouri, Abdenour, Filipe, Virginie, Barrault, Camille, Costes, Laurent, Hagège, Hervé, Merbah, Soraya, Carrier, Paul, Debette-Gratien, Maryline, Jacques, Jérémie, Lassailly, Guillaume, Artu, Florent, Canva, Valérie, Dharancy, Sébastien, Louvet, Alexandre, Latournerie, Marianne, Bardou, Marc, Mouillot, Thomas, Bacq, Yannick, Barbereau, Didier, Nicolas, Charlotte, Chevalier, Caroline, Archambeaud, Isabelle, Habes, Sarah, Botta-Fridlund, Danièle, Saillard, Eric, Lafrance, Marie-Josée, Cacoub, Patrice, Carrat, Fabrice, Carrieri, Patrizia, Delarocque-Astagneau, Elisabeth, De Ledinghen, Victor, Dorival, Céline, Dubuisson, Jean, Housset, Chantal, Larrey, Dominique, Marcellin, Patrick, Pawlotsky, Jean-Michel, Petrov-Sanchez, Ventzislava, Vaux, Sophie, Wittkop, Linda, Yazdanpanah, Yazdan, Zucman-Rossi, Jessica, Ganne-Carrié, Nathalie, Chaffaut, Cendrine, Moreno, Christophe, Moirand, Romain, Carbonell, Nicolas, Duclos-Vallée, Jean-Charles, de Ledinghen, Victor, Ozenne, Violaine, Henrion, Jean, Perlemuter, Gabriel, Amiot, Xavier, Chevret, Sylvie, Najean, Marie, Layese, Richard, Zarca, Kevin, Segar, Laeticia Blampain, Cagnot, Carole, N’Kontchou, Gisèle, Ronot, Maxime, Audureau, Etienne, and Durand-Zaleski, Isabelle

Published
2022
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36. Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial

Author

Yau, Thomas, Park, Joong-Won, Finn, Richard S, Cheng, Ann-Lii, Mathurin, Philippe, Edeline, Julien, Kudo, Masatoshi, Harding, James J, Merle, Philippe, Rosmorduc, Olivier, Wyrwicz, Lucjan, Schott, Eckart, Choo, Su Pin, Kelley, Robin Kate, Sieghart, Wolfgang, Assenat, Eric, Zaucha, Renata, Furuse, Junji, Abou-Alfa, Ghassan K, El-Khoueiry, Anthony B, Melero, Ignacio, Begic, Damir, Chen, Gong, Neely, Jaclyn, Wisniewski, Tami, Tschaika, Marina, and Sangro, Bruno

Published
2022
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37. Dysregulation of serum bile acids and FGF19 in alcoholic hepatitis

Author

Brandl, Katharina, Hartmann, Phillipp, Jih, Lily J, Pizzo, Donald P, Argemi, Josepmaria, Ventura-Cots, Meritxell, Coulter, Sally, Liddle, Christopher, Ling, Lei, Rossi, Stephen J, DePaoli, Alex M, Loomba, Rohit, Mehal, Wajahat Z, Fouts, Derrick E, Lucey, Michael R, Bosques-Padilla, Francisco, Mathurin, Philippe, Louvet, Alexander, Garcia-Tsao, Guadalupe, Verna, Elizabeth C, Abraldes, Juan G, Brown, Robert S, Vargas, Victor, Altamirano, Jose, Caballería, Juan, Shawcross, Debbie, Stärkel, Peter, Ho, Samuel B, Bataller, Ramon, and Schnabl, Bernd

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Substance Misuse, Genetics, Chronic Liver Disease and Cirrhosis, Liver Disease, Hepatitis, Digestive Diseases, Alcoholism, Alcohol Use and Health, 2.1 Biological and endogenous factors, Aetiology, Oral and gastrointestinal, Good Health and Well Being, Bile Acids and Salts, Biomarkers, Cholestasis, Correlation of Data, Female, Fibroblast Growth Factors, Hepatitis, Alcoholic, Humans, Male, Middle Aged, Neutrophil Infiltration, Neutrophils, Severity of Illness Index, Signal Transduction, FGF19, Bile acids, Microbiome, Public Health and Health Services, Gastroenterology & Hepatology, Clinical sciences
Abstract

Background & aimsThe degree of cholestasis is an important disease driver in alcoholic hepatitis, a severe clinical condition that needs new biomarkers and targeted therapies. We aimed to identify the largely unknown mechanisms and biomarkers linked to cholestasis in alcoholic hepatitis.MethodsHerein, we analyzed a well characterized cohort of patients with alcoholic hepatitis and correlated clinical and histological parameters and outcomes with serum bile acids and fibroblast growth factor 19 (FGF19), a major regulator of bile acid synthesis.ResultsWe found that total and conjugated bile acids were significantly increased in patients with alcoholic hepatitis compared with controls. Serum FGF19 levels were strongly increased and gene expression of FGF19 was induced in biliary epithelial cells and ductular cells of patients with alcoholic hepatitis. De novo bile acid synthesis (CYP7A1 gene expression and C4 serum levels) was significantly decreased in patients with alcoholic hepatitis. Importantly, total and conjugated bile acids correlated positively with FGF19 and with disease severity (model for end-stage liver disease score). FGF19 correlated best with conjugated cholic acid, and model for end-stage liver disease score best with taurine-conjugated chenodeoxycholic acid. Univariate analysis demonstrated significant associations between FGF19 and bilirubin as well as gamma glutamyl transferase, and negative correlations between FGF19 and fibrosis stage as well as polymorphonuclear leukocyte infiltration, in all patients with alcoholic hepatitis.ConclusionSerum FGF19 and bile acids are significantly increased in patients with alcoholic hepatitis, while de novo bile acid synthesis is suppressed. Modulation of bile acid metabolism or signaling could represent a promising target for treatment of alcoholic hepatitis in humans.Lay summaryUnderstanding the underlying mechanisms that drive alcoholic hepatitis is important for the development of new biomarkers and targeted therapies. Herein, we describe a molecule that is increased in patients with alcoholic hepatitis. Modulating the molecular pathway of this molecule might lead to promising targets for the treatment of alcoholic hepatitis.

Published
2018

38. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis

Author

Younossi, Zobair M, Loomba, Rohit, Anstee, Quentin M, Rinella, Mary E, Bugianesi, Elisabetta, Marchesini, Giulio, Neuschwander‐Tetri, Brent A, Serfaty, Lawrence, Negro, Francesco, Caldwell, Stephen H, Ratziu, Vlad, Corey, Kathleen E, Friedman, Scott L, Abdelmalek, Manal F, Harrison, Stephen A, Sanyal, Arun J, Lavine, Joel E, Mathurin, Philippe, Charlton, Michael R, Goodman, Zachary D, Chalasani, Naga P, Kowdley, Kris V, George, Jacob, and Lindor, Keith

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Liver Disease, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Clinical Research, Hepatitis, Oral and gastrointestinal, Good Health and Well Being, Biomarkers, Collagen, Humans, Liver, Liver Cirrhosis, Non-alcoholic Fatty Liver Disease, Medical Biochemistry and Metabolomics, Immunology, Gastroenterology & Hepatology, Clinical sciences
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a spectrum comprised of isolated steatosis, nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. The majority of NAFLD subjects do not have NASH and do not carry a significant risk for liver-related adverse outcomes (cirrhosis and mortality). Globally, the prevalence of NAFLD is approximately 25%. In Asia, a gradient of high to low prevalence rates is noted from urban to rural areas. Given the prevalence of NAFLD, the clinical and economic burden of NAFLD and NASH can be substantial. With increasing recognition of NASH as an important liver disease, the diagnosis of NASH still requires a liver biopsy that is suboptimal. Although liver biopsy is the most accurate modality to diagnose and stage the severity of NASH, this method suffers from being invasive, costly, associated with potential complications, and plagued with interobserver variability of individual pathological features. A number of noninvasive modalities to diagnose NASH and stage liver fibrosis are being developed. These modalities include predictive models (NAFLD fibrosis score) and serum biomarkers such as enhanced liver fibrosis (ELF). Other tests are based on radiological techniques, such as transient elastography (TE) or magnetic resonance elastography (MRE), which are used to estimate liver stiffness as a potential surrogate of hepatic fibrosis. Although a dynamic field of research, most of these diagnostic modalities have area under the curve ranging between 0.76 and 0.90%, with MRE having the best predictive performance. In summary, developing safe and easily accessible noninvasive modalities to accurately diagnose and monitor NASH and associated fibrosis is of utmost importance in clinical practice and clinical research. These tests are not only important to risk stratify subjects at the greatest risk for progressive liver disease, but also to serve as appropriate surrogate endpoints for therapeutic clinical trials of NASH. (Hepatology 2018;68:349-360).

Published
2018

39. Current and future therapeutic regimens for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis

Author

Younossi, Zobair M, Loomba, Rohit, Rinella, Mary E, Bugianesi, Elisabetta, Marchesini, Giulio, Neuschwander‐Tetri, Brent A, Serfaty, Lawrence, Negro, Francesco, Caldwell, Stephen H, Ratziu, Vlad, Corey, Kathleen E, Friedman, Scott L, Abdelmalek, Manal F, Harrison, Stephen A, Sanyal, Arun J, Lavine, Joel E, Mathurin, Philippe, Charlton, Michael R, Chalasani, Naga P, Anstee, Quentin M, Kowdley, Kris V, George, Jacob, Goodman, Zachary D, and Lindor, Keith

Subjects
Hepatitis, Liver Disease, Chronic Liver Disease and Cirrhosis, Prevention, Clinical Trials and Supportive Activities, Clinical Research, Digestive Diseases, Rare Diseases, Oral and gastrointestinal, Good Health and Well Being, Clinical Trials as Topic, Exercise, Humans, Liver Transplantation, Non-alcoholic Fatty Liver Disease, Obesity, Weight Loss, Medical Biochemistry and Metabolomics, Clinical Sciences, Immunology, Gastroenterology & Hepatology
Abstract

Nonalcoholic fatty liver disease (NAFLD) and its progressive form non-alcoholic steatohepatitis (NASH), are rapidly becoming among the top causes of cirrhosis, hepatocellular carcinoma, and indications for liver transplantation. Other than lifestyle modification through diet and exercise, there are currently no other approved treatments for NASH/NAFLD. Although weight loss can be effective, it is difficult to achieve and sustain. In contrast, bariatric surgery can improve metabolic conditions associated with NAFLD, and has been shown to improve liver histology. To have approved regimens for the treatment of NASH/NAFLD, several issues must be addressed. First, all stakeholders must agree on the most appropriate clinical trial endpoints for NASH. Currently, resolution of NASH (without worsening fibrosis) or reduction of fibrosis stage (without worsening NASH) are the accepted endpoints by the regulatory authorities. It is important to recognize the prognostic implication of histologic features of NASH. In this context, although histologic NASH has been associated with advanced fibrosis, it is not an independent predictor of long-term mortality. In contrast, there are significant data to suggest that fibrosis stage is the only robust and independent predictor of liver-related mortality. In addition to the primary endpoints, several important secondary endpoints, including noninvasive biomarkers, long-term outcomes, and patient-reported outcomes must be considered. In 2018, a few phase 3 clinical trials for the treatment of NASH have been initiated. Additionally, a number of phase 2a and 2b clinical trials targeting different pathogenic pathways in NASH are in the pipeline of emerging therapies.ConclusionOver the next 5 years, some of these regimens are expected to provide potential new treatment options for patients with NASH/NAFLD. (Hepatology 2018;68:361-371).

Published
2018

40. The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity.

Author

Bricambert, Julien, Alves-Guerra, Marie-Clotilde, Esteves, Pauline, Prip-Buus, Carina, Bertrand-Michel, Justine, Guillou, Hervé, Chang, Christopher J, Vander Wal, Mark N, Canonne-Hergaux, François, Mathurin, Philippe, Raverdy, Violeta, Pattou, François, Girard, Jean, Postic, Catherine, and Dentin, Renaud

Subjects
Liver, Cells, Cultured, Animals, Mice, Inbred C57BL, Mice, Knockout, Humans, Mice, Obesity, Glucose, Glutathione, Homeodomain Proteins, Nuclear Proteins, Histones, Transcription Factors, Enzyme Activation, Methylation, Oxidative Stress, Male, Pentose Phosphate Pathway, NF-E2-Related Factor 2, Promoter Regions, Genetic, Histone Demethylases, Non-alcoholic Fatty Liver Disease, Demethylation, Digestive Diseases, Prevention, Liver Disease, Chronic Liver Disease and Cirrhosis, Genetics, Nutrition, 2.1 Biological and endogenous factors, Metabolic and Endocrine, Cancer, Cells, Cultured, Inbred C57BL, Knockout, Promoter Regions, Genetic
Abstract

Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator of the transcription factor Carbohydrate Responsive Element Binding Protein (ChREBP). By specifically erasing H3K9me2 methyl-marks on the promoter of ChREBP-regulated genes, Phf2 facilitates incorporation of metabolic precursors into mono-unsaturated fatty acids, leading to hepatosteatosis development in the absence of inflammation and insulin resistance. Moreover, the Phf2-mediated activation of the transcription factor NF-E2-related factor 2 (Nrf2) further reroutes glucose fluxes toward the pentose phosphate pathway and glutathione biosynthesis, protecting the liver from oxidative stress and fibrogenesis in response to diet-induced obesity. Overall, our findings establish a downstream epigenetic checkpoint, whereby Phf2, through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of NAFLD.

Published
2018

41. Evaluation of laboratory tests for cirrhosis and for alcohol use, in the context of alcoholic cirrhosis.

Author

Whitfield, John, Masson, Steven, Liangpunsakul, Suthat, Hyman, Jessica, Mueller, Sebastian, Aithal, Guruprasad, Eyer, Florian, Gleeson, Dermot, Thompson, Andrew, Stickel, Felix, Soyka, Michael, Daly, Ann, Cordell, Heather, Liang, Tiebing, Foroud, Tatiana, Lumeng, Lawrence, Pirmohamed, Munir, Nalpas, Bertrand, Bence, Camille, Jacquet, Jean-Marc, Louvet, Alexandre, Moirand, Romain, Nahon, Pierre, Naveau, Sylvie, Perney, Pascal, Podevin, Philippe, Haber, Paul, Seitz, Helmut, Day, Christopher, Mathurin, Philippe, Morgan, Timothy, and Seth, Devanshi

Subjects
Abstinence, Alcohol, Aspartate aminotransferase, Cirrhosis, Gamma glutamyl transferase, Adult, Alcohol Abstinence, Alcohol Drinking, Area Under Curve, Aspartate Aminotransferases, Bilirubin, Biomarkers, Case-Control Studies, Clinical Enzyme Tests, Europe, Female, Humans, International Normalized Ratio, Liver Cirrhosis, Alcoholic, Liver Function Tests, Male, Middle Aged, Predictive Value of Tests, ROC Curve, Reproducibility of Results, Risk Factors, Sex Factors, United States, gamma-Glutamyltransferase
Abstract

Laboratory tests can play an important role in assessment of alcoholic patients, including for evaluation of liver damage and as markers of alcohol intake. Evidence on test performance should lead to better selection of appropriate tests and improved interpretation of results. We compared laboratory test results from 1578 patients between cases (with alcoholic cirrhosis; 753 men, 243 women) and controls (with equivalent lifetime alcohol intake but no liver disease; 439 men, 143 women). Comparisons were also made between 631 cases who had reportedly been abstinent from alcohol for over 60 days and 364 who had not. ROC curve analysis was used to estimate and compare tests ability to distinguish patients with and without cirrhosis, and abstinent and drinking cases. The best tests for presence of cirrhosis were INR and bilirubin, with areas under the ROC curve (AUCs) of 0.91 ± 0.01 and 0.88 ± 0.01, respectively. Confining analysis to patients with no current or previous ascites gave AUCs of 0.88 ± 0.01 for INR and 0.85 ± 0.01 for bilirubin. GGT and AST showed discrimination between abstinence and recent drinking in patients with cirrhosis, including those without ascites, when appropriate (and for GGT, sex-specific) limits were used. For AST, a cut-off limit of 85 units/L gave 90% specificity and 37% sensitivity. For GGT, cut-off limits of 288 units/L in men and 138 units/L in women gave 90% specificity for both and 40% sensitivity in men, 63% sensitivity in women. INR and bilirubin show the best separation between patients with alcoholic cirrhosis (with or without ascites) and control patients with similar lifetime alcohol exposure. Although AST and GGT are substantially increased by liver disease, they can give useful information on recent alcohol intake in patients with alcoholic cirrhosis when appropriate cut-off limits are used.

Published
2018

43. Prevalence and impact of alcohol abstinence in alcohol‐associated cirrhosis: Systematic review and meta‐analysis

Author

Lim, Wen Hui, primary, Tay, Phoebe, additional, Ng, Cheng Han, additional, Tan, Darren Jun Hao, additional, Ong, Christen, additional, Koh, Jia Hong, additional, Teng, Margaret, additional, Chee, Douglas, additional, Wong, Zhen Yu, additional, Kawaguchi, Takumi, additional, Takahashi, Hirokazu, additional, Muthiah, Mark, additional, Tan, Eunice X. X., additional, Wijarnpreecha, Karn, additional, Lee, Guan Huei, additional, Noureddin, Mazen, additional, Lee, Brian P., additional, Mathurin, Philippe, additional, Loomba, Rohit, additional, and Huang, Daniel Q., additional

Published
2024
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45. Impact of cirrhosis aetiology on incidence and prognosis of hepatocellular carcinoma diagnosed during surveillance

Author

Ganne-Carrié, Nathalie, Chaffaut, Cendrine, Archambeaud, Isabelle, d’Alteroche, Louis, Oberti, Frédéric, Roulot, Dominique, Moreno, Christophe, Louvet, Alexandre, Dao, Thông, Moirand, Romain, Goria, Odile, Nguyen-Khac, Eric, Carbonell, Nicolas, Duclos-Vallée, Jean-Charles, Pol, Stanislas, de Ledinghen, Victor, Ozenne, Violaine, Henrion, Jean, Péron, Jean-Marie, Tran, Albert, Perlemuter, Gabriel, Amiot, Xavier, Zarski, Jean-Pierre, Chevret, Sylvie, Nahon, Pierre, Asselah, Tarik, Guyader, Dominique, Fontaine, Hélène, Pageaux, Georges-Philippe, De Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Bronowicki, Jean-Pierre, Decaens, Thomas, Riachi, Ghassan, Calès, Paul, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Dharancy, Sebastien, Blanc, Jean-Frédéric, Abergel, Armand, Chazouillères, Olivier, Mallat, Ariane, Grangé, Jean-Didier, Attali, Pierre, Wartelle, Claire, Thabut, Dominique, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Bernard-Chabert, Brigitte, Hillaire, Sophie, Di Martino, Vincent, N’Kontchou, Gisèle, Layese, Richard, and Audureau, Etienne

Published
2021
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46. Including Ratio of Platelets to Liver Stiffness Improves Accuracy of Screening for Esophageal Varices That Require Treatment

Author

Huvelin, Sylvie Sacher, Calès, Paul, Valla, Dominique, Bureau, Christophe, Olivier, Anne, Oberti, Frédéric, Boursier, Jérôme, Galmiche, Jean Paul, Vinel, Jean Pierre, Duburque, Clotilde, Attar, Alain, Archambeaud, Isabelle, Benamouzig, Robert, Gaudric, Marianne, Luet, Dominique, Couzigou, Patrice, Planche, Lucie, Coron, Emmanuel, Hiriart, Jean-Baptiste, Chermak, Faiza, Charbonnier, Maude, Nahon, Pierre, Marcellin, Patrick, Guyader, Dominique, Pol, Stanislas, Fontaine, Hélène, Larrey, Dominique, De Lédinghen, Victor, Ouzan, Denis, Zoulim, Fabien, Roulot, Dominique, Tran, Albert, Bronowicki, Jean-Pierre, Zarski, Jean-Pierre, Leroy, Vincent, Riachi, Ghassan, Péron, Jean-Marie, Alric, Laurent, Bourlière, Marc, Mathurin, Philippe, Dharancy, Sebastien, Blanc, Jean-Frédéric, Abergel, Armand, Serfaty, Lawrence, Mallat, Ariane, Grangé, Jean-Didier, Attali, Pierre, Bacq, Yannick, Wartelle, Claire, Dao, Thông, Benhamou, Yves, Pilette, Christophe, Silvain, Christine, Christidis, Christos, Capron, Dominique, Thiefin, Gérard, Hillaire, Sophie, Di Martino, Vincent, Berger, Arthur, Ravaioli, Federico, Farcau, Oana, Festi, Davide, Stefanescu, Horia, Buisson, François, Ganne-Carriè, Nathalie, Berzigotti, Annalisa, de Ledinghen, Victor, and Petta, Salvatore

Published
2021
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48. Selonsertib for patients with bridging fibrosis or compensated cirrhosis due to NASH: Results from randomized phase III STELLAR trials

Author

Gadano, Adrian, Martins, Marcelo, Angus, Peter, Bate, John, Danta, Mark, George, Jacob, Hodge, Alexander, Kontorinis, Nickolas, Roberts, Stuart, Sanagapalli, Santosh, Skoien, Richard, Thompson, Alexander, Zekry, Amany, Stauber, Rudolf, Trauner, Michael, Moreno, Christophe, Reynaert, Hendrik, Verbeke, Len, Silva, Mario Reis Alvares da, Parise, Edison, Oliveira, Claudia Pinto Marques Souza de, Araujo, Roberta Chaves, Martinelli, Ana de Lourdes Candolo, Borman, Meredith, Chandok, Natasha, Elkhashab, Magdy, Fraser, Hughie, Kaita, Kelly, Ma, Mang, Marotta, Paul, Ramji, Alnoor, Tam, Edward, Yoshida, Eric, Swain, Mark, Sebastiani, Giada, Petrunia, Denis, Abergel, Armando, Anty, Rodolphe, Bourlière, Marc, Boursier, Jérôme, Bureau, Christophe, Castera, Laurent, Habersetzer, François, Hézode, Christophe, Ledinghen, Victor De, Leroy, Vincent, Loustaud-Ratti, Véronique, Mathurin, Philippe, Pol, Stanislas, Zoulim, Fabien, Hinrichsen, Holger, Ingiliz, Patrick, Lammert, Frank, Manns, Michael, Schattenberg, Jörn, Schiefke, Ingolf, Trautwein, Christian, Zeuzem, Stefan, Hui, Aric, Li, King-Kong, Wong, Vincent, Acharya, Subrat, Chowdhury, Abhijit, Duseja, Ajay, Kapoor, Dharmesh, Mukewar, Shrikant, Sarin, Shiv, Shah, Samir, Shalimar, Sood, Ajit, Tantry, BV, Ben-Ari, Ziv, Katchman, Helena, Safadi, Rifaat, Veitsman, Ella, Zuckerman, Eli, Brunetto, Maurizia, Lampertico, Pietro, Mangia, Alessandra, Akahane, Takemi, Akuta, Norio, Eguchi, Yuichiro, Fujiyama, Shigetoshi, Genda, Takuya, Hiasa, Yoichi, Ido, Akio, Ikeda, Fusao, Ikegami, Tadashi, Imajo, Kento, Itoh, Yoshito, Iwasa, Motoh, Karino, Yoshiyasu, Kato, Naoya, Kawaguchi, Takumi, Kawanaka, Miwa, Kido, Masahiro, Kobayashi, Tomoo, Kurosaki, Masayuki, Matsuzaki, Yasushi, Mita, Eiji, Mizukoshi, Eishiro, Nakahara, Takashi, Nomura, Hideyuki, Notsumata, Kazuo, Okanoue, Takeshi, Saito, Satoshi, Sakugawa, Hiroshi, Suzuki, Yoshiyuki, Takaguchi, Koichi, Takaki, Akinobu, Takashima, Tomoyuki, Tanaka, Saiyu, Tsuji, Keiji, Ueno, Yoshiyuki, Umemura, Takeji, Uto, Hirofumi, Yamashita, Nobuyuki, Yanase, Mikio, Yatsuhashi, Hiroshi, Yoneda, Masashi, Chan, Wah Kheong, Tan, Soek Siam, Garza, Laura Cisneros, Ladron De Guevara Cetina, Alma, Angeles, Rocio Guadalupe Vargas, Silva, Francisca Martinez, Van Erpecum, Karel, Orr, David, Jabłkowski, Maciej, Jaroszewicz, Jerzy, Ramos, Jose, Ahmed, Taufique, Ang, Tiing, Dan, Yock young, Goh, Boon Bee, Kaliyaperumal, Kalaiyarasi, Yip, Cherng Hann, Baik, Soon Koo, Jang, Byoung Kuk, Jun, Dae Won, Kim, Won, Kim, Hyung Joon, Kim, Ji Hoon, Lee, Kwan Sik, Lee, Chun Kyon, Lim, Young-Suk, Park, Jun Yong, Tak, Won Young, Augustin, Salvador, Perez, Salvador Benlloch, Caballeria, Juan, Luis, Jose, Panero, Calleja, Rodríguez, Jose Carrión, Garcia, Javier Crespo, Samaniego, Javier Garcia, Gibert, Pere Ginès, Prieto, Martin, Gomez, Manuel Romero, Turnes, Juan, Dufour, Jean-Francois, Moriggia, Alberto, Sheen, I-Shyan, Kao, Jia-Horng, Cheng, Pin-Nan, Huang, Jee-Fu, Yang, Sheng-Shun, Su, Wei-Wen, Chen, Chi-Yi, Chien, Rong-Nan, Lo, Gin-Ho, Chu, Chi-Jen, Wang, Horng-Yuan, Hu, Jui-Ting, Huang, Yi Wen, Agarwal, Kosh, Allison, Michael, Anstee, Quentin, Austin, Andrew, Fowell, Andrew, Ch'ng, Chin Lye, Manousou, Pinelopi, Newsome, Philip, Ryder, Stephen, Shankar, Arun, Abdelmalek, Manal, Abrams, Gary, Aguilar, Humberto, Alam, Imtiaz, Alba, Laura, Alkhouri, Naim, Allen, Alina, Aqel, Bashar, Balart, Luis, Barritt, A. Sidney, IV, Behari, Jaideep, Bennett, Michael, Bernstein, David, Bhandari, Bal Raj, Bonacini, Maurizio, Borg, Brian, Brown, Kimberly, Bzowej, Natalie, Caldwell, Stephen, Chami, Tawfik, Coates, Allan, Cueli, Adolfo, Davis, Mitchell, deLemos, Andrew, Desai, Archita, Dunn, Winston, Ferreira, Nelson, Fine, Michael, Firpi-Morell, Roberto, Freedland, Curtis, Freilich, Bradley, Fuchs, Michael, Galambos, Michael, Gallegos-Orozco, Juan, Galler, Greg, Ghali, Maged, Ghalib, Reem, Gill, Satinder, Gillis, Marcum, Gilroy, Richard, Gordon, Stuart, Gunn, Nadege, Halegoua-DeMarzio, Dina, Hassan, Mohamed, Hassanein, Tarek, Herring, Robert, Jr., Hong, John, Huang, Jonathan, Kabler, Heidi, Kayali, Zeid, Knapple, Whitfield, Kolli, Geetha, Kowdley, Kris, Krause, Richard, Lawitz, Eric, Lidofsky, Steven, Lim, Joseph, Lipkis, Donald, Loomba, Rohit, Mahgoub, Amar, Malespin, Miguel, Manch, Richard, Mannis, Steven, Manos, Paul, McDonald, Thomas, McKenzie, Mark, Mena, Edward, Merriman, Raphael, Moehlen, Martin William, Montgomery, Richard, Murphy, Robert, Natarajan, Yamini, Neff, Guy, Noureddin, Mazen, Ortiz-Lasanta, Grisell, Pagadala, Mangesh, Patel, Keyur, Patton, Heather, Peyton, Adam, Pimstone, Neville, Poulos, John, Pound, David, Pyrsopoulos, Nikolaos, Rafiq, Nila, Ravendhran, Natarajan, Ravinuthala, Ravi, Reddy, K. Rajendar, Reindollar, Robert, Reynolds, Justin, Rinella, Mary, Rizvi, Syed, Rockey, Don, Rodriguez-Perez, Federico, Ruane, Peter, Rubin, Raymond, Ryan, Michael, Saeian, Kia, Sanyal, Arun, Sarkar, Souvik, Scanga, Andrew, Schiff, Eugene, Schmidt, Warren, Schneider, Jeffrey, Sepe, Thomas, Shah, Dhiren, Shaikh, Obaid, Shankar, Uday, Sheikh, Aasim, Sheikh, Muhammad, Sherman, Kenneth, Shiffman, Mitchell, Siddique, Asma, Smith, Matthew, Suarez, Rosa, Talal, Andrew, Te, Helen, Tekola, Bezawit, Tetri, Brent, Thuluvath, Paul, Toro, Doris, Torres, Dawn, Trinh, Huy, Trotter, James, Vento, Angel, Vierling, John, Vuppalanchi, Raj, Waters, Michael, Weisberg, Ilan, Wieland, Amanda, Williams, Alonzo, Younes, Ziad, Adams, Leon, Harding, Damian, Hodge, Alex, Kontorinis, Nick, Strasser, Simone, Thompson, Alex, Horsmans, Yves, Steenkiste, Christophe Van, Bailey, Robert, Giard, Jeanne-Marie, Montano-Loza, Aldo, Puglia, Marco, Tsoi, Keith, Larrey, Dominique, Nguyen-Khac, Eric, Ratziu, Vlad, Spengler, Ulrich, Wiegand, Johannes, Hui, Aric Josun, Acharya, Subrat Kumar, Sarin, Shiv Kumar, Tantry, Vishwanath, Braun, Marius, Hazzan, Rawi, Lurie, Yoav, Colombo, Massimo, Fujii, Hideki, Hashimoto, Etsuko, Kato, Masaki, Ogawa, Koji, Takehara, Tetsuo, Tokushige, Katsutoshi, Garza, Laura Esthela Cisneros, Ladrón De Guevara, Alma Laura, Schultz, Michael, Janczewska, Ewa, Toro, Doris H., Jeong, Sook-Hyang, Kim, Yoon Jun, Lee, Jin-Woo, Ang, Tiing Leong, Bee, George Goh Boon, Benlloch, Salvador, Caballería, Juan, Calleja, José Luis, Rodríguez, Jose A. Carrión, Crespo, Javier, Diago, Moises, Fernandez-Rodriguez, Conrado, García-Samaniego, Javier, Ginès, Pere, Romero, Manuel, Dufour, Jean-François, Alazawi, William, Ch'ng, Chin-Lye, Forton, Daniel, Priest, Matthew, Sheridan, David, Ankoma-Sey, Victor, Balakrishnan, Maya, Bambha, Kiran, Barritt, A. Sidney, Bhandari, Bal, Brandman, Danielle, Chang, Charissa, Corey, Kathleen, Feldman, Michael, Gholam, Pierre, Goff, John, Marzio, Dina Halegoua-De, Harrison, Stephen, Hellstern, Paul, Jr., Herring, Robert, Iyer, Rajalakshmi, Jakiche, Antoine, Kohli, Anita, Krok, Karen, Kugelmas, Marcelo, Kumar, Sonal, Lai, Michelle, Mahmoud, Mitchell, Mantry, Parvez, Marsano, Luis, Nguyen, Tuan, Park, James, Patton, Heather M., Pockros, Paul, Reddy, Rajender, Rodriguez, Miguel, Sarles, Harry, Satapathy, Sanjaya, Sedghi, Shahriar, Shah, Nikunj, Sheikh, Muhammad Yasin, Sigal, Samuel, Stanca, Carmen, Steinbook, Michael, Szabo, Gyongyi, Terrault, Norah, Tong, Myron, Victor, David, Zervos, Xaralambos, Harrison, Stephen A., Wong, Vincent Wai-Sun, Caldwell, Stephen H., Shiffman, Mitchell L., Camargo, Marianne, Li, Georgia, Kersey, Kathryn, Jia, Catherine, Zhu, Yanni, Djedjos, C. Stephen, Subramanian, G. Mani, Myers, Robert P., Anstee, Quentin M., Romero-Gomez, Manuel, Goodman, Zachary, Lawitz, Eric J., and Younossi, Zobair

Published
2020
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