2,874 results on '"Sanyal, Arun J."'
Search Results
2. Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement
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Lee, Brian P., Witkiewitz, Katie, Mellinger, Jessica, Anania, Frank A., Bataller, Ramon, Cotter, Thomas G., Curtis, Brenda, Dasarathy, Srinivasan, DeMartini, Kelly S., Diamond, Ivan, Diazgranados, Nancy, DiMartini, Andrea F., Falk, Daniel E., Fernandez, Anne C., German, Margarita N., Kamath, Patrick S., Kidwell, Kelley M., Leggio, Lorenzo, Litten, Raye, Louvet, Alexandre, Lucey, Michael R., McCaul, Mary E., Sanyal, Arun J., Singal, Ashwani K., Sussman, Norman L., Terrault, Norah A., Thursz, Mark R., Verna, Elizabeth C., Radaeva, Svetlana, Nagy, Laura E., and Mitchell, Mack C.
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- 2024
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3. Sex and Race-Ethnic Disparities in Metabolic Dysfunction-Associated Steatotic Liver Disease: An Analysis of 40,166 Individuals
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Fu, Clarissa Elysia, Teng, Margaret, Tung, Daniel, Ramadoss, Vijay, Ong, Christen, Koh, Benjamin, Lim, Wen Hui, Tan, Darren Jun Hao, Koh, Jia Hong, Nah, Benjamin, Syn, Nicholas, Tamaki, Nobuharu, Siddiqui, Mohammad Shadab, Wijarnpreecha, Karn, Ioannou, George N., Nakajima, Atsushi, Noureddin, Mazen, Sanyal, Arun J., Ng, Cheng Han, and Muthiah, Mark
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- 2024
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4. Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis
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Harrison, Stephen A, Ratziu, Vlad, Anstee, Quentin M, Noureddin, Mazen, Sanyal, Arun J, Schattenberg, Jörn M, Bedossa, Pierre, Bashir, Mustafa R, Schneider, David, Taub, Rebecca, Bansal, Meena, Kowdley, Kris V, Younossi, Zobair M, and Loomba, Rohit
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Clinical Trials and Supportive Activities ,Liver Disease ,Hepatitis ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Detection ,screening and diagnosis ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,4.2 Evaluation of markers and technologies ,Oral and gastrointestinal ,Good Health and Well Being ,Adult ,Humans ,Non-alcoholic Fatty Liver Disease ,Liver ,Liver Cirrhosis ,Biomarkers ,Pharmacology and Pharmaceutical Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
BackgroundNon-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) associated with steatosis, hepatocellular injury, inflammation and fibrosis. In a Phase 2 trial in adults with NASH (NCT02912260), resmetirom, an orally administered, liver-targeted thyroid hormone receptor-β selective agonist, significantly reduced hepatic fat (via imaging) and resolved NASH without worsening fibrosis (via liver biopsy) in a significant number of patients compared with placebo.AimsTo present the design of the Phase 3 MAESTRO clinical programme evaluating resmetirom for treatment of NASH (MAESTRO-NAFLD-1 [NCT04197479], MAESTRO-NAFLD-OLE [NCT04951219], MAESTRO-NASH [NCT03900429], MAESTRO-NASH-OUTCOMES [NCT05500222]).MethodsMAESTRO-NASH is a pivotal serial biopsy trial in up to 2000 adults with biopsy-confirmed at-risk NASH. Patients are randomised to a once-daily oral placebo, 80 mg resmetirom, or 100 mg resmetirom. Liver biopsies are conducted at screening, week 52 and month 54. MAESTRO-NAFLD-1 is a 52-week safety trial in ~1400 adults with NAFLD/presumed NASH (based on non-invasive testing); ~700 patients from MAESTRO-NAFLD-1 are enrolled in MAESTRO-NAFLD-OLE, a 52-week active treatment extension to further evaluate safety. MAESTRO-NASH-OUTCOMES is enrolling 700 adults with well-compensated NASH cirrhosis to evaluate the potential for resmetirom to slow progression to hepatic decompensation events. Non-invasive tests (biomarkers, imaging) are assessed longitudinally throughout, in addition to validated patient-reported outcomes.ConclusionThe MAESTRO clinical programme was designed in conjunction with regulatory authorities to support approval of resmetirom for treatment of NASH. The surrogate endpoints, based on week 52 liver biopsy, serum biomarkers and imaging, are confirmed by long-term clinical liver-related outcomes in MAESTRO-NASH (month 54) and MAESTRO-NASH-OUTCOMES (time to event).
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- 2024
5. Impact of age on NIS2+™ and other non-invasive blood tests for the evaluation of liver disease and detection of at-risk MASH
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Anstee, Quentin M, Magnanensi, Jeremy, Hajji, Yacine, Caron, Alexandra, Majd, Zouher, Rosenquist, Christian, Hum, Dean W, Staels, Bart, Connelly, Margery A, Loomba, Rohit, Harrison, Stephen A, Ratziu, Vlad, and Sanyal, Arun J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Liver Disease ,Digestive Diseases ,Oral and gastrointestinal ,Clinical sciences - Published
- 2024
6. A multisociety Delphi consensus statement on new fatty liver disease nomenclature
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Rinella, Mary E, Lazarus, Jeffrey V, Ratziu, Vlad, Francque, Sven M, Sanyal, Arun J, Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F, Anstee, Quentin M, Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher D, Narro, Graciela E Castro, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna R, Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D, Harrison, Stephen A, Kim, Seung Up, Koot, Bart G, Korenjak, Marko, Kowdley, Kris V, Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R, Powell, Elisabeth E, Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C, Spearman, C Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B, Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, Newsome, Philip N, and group, NAFLD Nomenclature consensus
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Digestive Diseases ,Clinical Research ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,Substance Misuse ,Oral and gastrointestinal ,Good Health and Well Being ,Female ,Male ,Humans ,Non-alcoholic Fatty Liver Disease ,Delphi Technique ,Ethanol ,Consensus ,Hepatomegaly ,NAFLD Nomenclature consensus group ,ALD ,Delphi ,MASH ,MASLD ,Met-ALD ,NAFLD ,alcohol ,metabolic ,nomenclature ,stigma ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and non-stigmatising, and can improve awareness and patient identification.
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- 2023
7. What Is the Best Treatment to Utilize in a Patient With Fatty Liver Disease and Type 2 Diabetes Mellitus?
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Sanyal, Arun J., primary and Puri, Puneet, additional
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- 2024
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8. Which Patients With Fatty Liver Disease on Ultrasound Require a Liver Biopsy?
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Sanyal, Arun J., primary and Reid, B. Marie, additional
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- 2024
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9. Can a Patient of Normal Body Weight, a Normal Serum Cholesterol Level, and No History of Diabetes Have Fatty Liver Disease?
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Sanyal, Arun J., primary
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- 2024
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10. My Patient With Chronic Hepatitis C Also Has Evidence of Nonalcoholic Steatohepatitis on His Liver Biopsy. What Can I Do to Increase His Chance of Responding to Peginterferon and Ribavirin Treatment?
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Sanyal, Arun J., primary and Cheung, Opang, additional
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- 2024
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11. An Obese Patient With Hypercholesterolemia Was Recently Started on a Statin and Is Now Found to Have Elevated Serum Liver Transaminases. Do I Need to Stop This Medication?
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Sanyal, Arun J., primary and Choudhury, Jayanta, additional
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- 2024
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12. Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH
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Loomba, Rohit, Sanyal, Arun J, Kowdley, Kris V, Bhatt, Deepak L, Alkhouri, Naim, Frias, Juan P, Bedossa, Pierre, Harrison, Stephen A, Lazas, Donald, Barish, Robert, Gottwald, Mildred D, Feng, Shibao, Agollah, Germaine D, Hartsfield, Cynthia L, Mansbach, Hank, Margalit, Maya, and Abdelmalek, Manal F
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Biomedical and Clinical Sciences ,Clinical Sciences ,Hepatitis ,Liver Disease ,Clinical Research ,Clinical Trials and Supportive Activities ,Digestive Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Humans ,Biopsy ,Double-Blind Method ,Fibroblast Growth Factors ,Fibrosis ,Gastrointestinal Agents ,Injections ,Subcutaneous ,Non-alcoholic Fatty Liver Disease ,Treatment Outcome ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPegozafermin is a long-acting glycopegylated (pegylated with the use of site-specific glycosyltransferases) fibroblast growth factor 21 (FGF21) analogue in development for the treatment of nonalcoholic steatohepatitis (NASH) and severe hypertriglyceridemia. The efficacy and safety of pegozafermin in patients with biopsy-proven noncirrhotic NASH are not well established.MethodsIn this phase 2b, multicenter, double-blind, 24-week, randomized, placebo-controlled trial, we randomly assigned patients with biopsy-confirmed NASH and stage F2 or F3 (moderate or severe) fibrosis to receive subcutaneous pegozafermin at a dose of 15 mg or 30 mg weekly or 44 mg once every 2 weeks or placebo weekly or every 2 weeks. The two primary end points were an improvement in fibrosis (defined as reduction by ≥1 stage, on a scale from 0 to 4, with higher stages indicating greater severity), with no worsening of NASH, at 24 weeks and NASH resolution without worsening of fibrosis at 24 weeks. Safety was also assessed.ResultsAmong the 222 patients who underwent randomization, 219 received pegozafermin or placebo. The percentage of patients who met the criteria for fibrosis improvement was 7% in the pooled placebo group, 22% in the 15-mg pegozafermin group (difference vs. placebo, 14 percentage points; 95% confidence interval [CI], -9 to 38), 26% in the 30-mg pegozafermin group (difference, 19 percentage points; 95% CI, 5 to 32; P = 0.009), and 27% in the 44-mg pegozafermin group (difference, 20 percentage points; 95% CI, 5 to 35; P = 0.008). The percentage of patients who met the criteria for NASH resolution was 2% in the placebo group, 37% in the 15-mg pegozafermin group (difference vs. placebo, 35 percentage points; 95% CI, 10 to 59), 23% in the 30-mg pegozafermin group (difference, 21 percentage points; 95% CI, 9 to 33), and 26% in the 44-mg pegozafermin group (difference, 24 percentage points; 95% CI, 10 to 37). The most common adverse events associated with pegozafermin therapy were nausea and diarrhea.ConclusionsIn this phase 2b trial, treatment with pegozafermin led to improvements in fibrosis. These results support the advancement of pegozafermin into phase 3 development. (Funded by 89bio; ENLIVEN ClinicalTrials.gov number, NCT04929483.).
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- 2023
13. Fibrosis Progression Rate in Biopsy-Proven Nonalcoholic Fatty Liver Disease Among People With Diabetes Versus People Without Diabetes: A Multicenter Study
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Huang, Daniel Q, Wilson, Laura A, Behling, Cynthia, Kleiner, David E, Kowdley, Kris V, Dasarathy, Srinivasan, Amangurbanova, Maral, Terrault, Norah A, Diehl, Anna Mae, Chalasani, Naga, Neuschwander-Tetri, Brent A, Sanyal, Arun J, Tonascia, James, Loomba, Rohit, Allende, Daniela, Bellar, Annette, Dasarathy, Jaividhya, Welch, Nicole, Yerrapothu, Rahul, Bashir, Mustafa, Guy, Cynthia, Kopping, Mariko, Piercy, Dawn, Suzuki, Ayako, Tawadrou, Naglaa, Cruz, Mandy, Cummings, Oscar W, Garrison, Lisa, Gawrieh, Samer, Samala, Niharika, Vuppalanchi, Raj, Carpenter, Danielle, Cattoor, Theresa, Freebersyser, Janet, Angkanaworakul, Pannapat, Berihun, Achashman, Buysse, Andrew, Dorrian, Theresa, Gulati, Breanna, Liu, Kevin, Misic, Sandra, Sohal, Adam, Vuong, Joseph, Ajmera, Veeral, Madamba, Egbert, Middleton, Michael S, Richards, Lisa, Singh, Seema, Sirlin, Claude, Gill, Ryan, Hameed, Bilal, Awe, Remilekun, Olvera, Daisy, Terrault, Norah, Yuan, Liyun, Yeh, Matthew, Albhaisi, Somaya, Asgharpour, Amon, Boyett, Sherry, Contos, Melissa J, Luketic, Velimir AC, Schlosser, Jolene, Siddiqui, Mohammad S, Adamo, Peggy, Belt, Patricia, Clark, Jeanne M, DeSanto, Jennifer M, Meinert, Jill, Miriel, Laura, Mitchell, Emily P, Shade, Carrie, Smith, Jacqueline, Smith, Michael, Sternberg, Alice, Van Natta, Mark L, Wagoner, Annette, Woreta, Tinsay, and Yates, Katherine P
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Biomedical and Clinical Sciences ,Clinical Sciences ,Hepatitis ,Liver Disease ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Diabetes ,Obesity ,Metabolic and endocrine ,Good Health and Well Being ,Adult ,Humans ,Female ,Male ,Non-alcoholic Fatty Liver Disease ,Diabetes Mellitus ,Type 2 ,Cohort Studies ,Liver Cirrhosis ,Biopsy ,Nonalcoholic Steatohepatitis ,NAFLD ,Cirrhosis ,Type 2 Diabetes Mellitus ,NASH Clinical Research Network ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Abstract
Background & aimsThere are limited data regarding fibrosis progression in biopsy-proven nonalcoholic fatty liver disease (NAFLD) in people with type 2 diabetes mellitus (T2DM) compared with people without T2DM. We assessed the time to fibrosis progression in people with T2DM compared with people without T2DM in a large, multicenter, study of people with NAFLD who had paired liver biopsies.MethodsThis study included 447 adult participants (64% were female) with NAFLD who had paired liver biopsies more than 1 year apart. Liver histology was systematically assessed by a central pathology committee blinded to clinical data. The primary outcome was the cumulative incidence of a ≥1-stage increase in fibrosis in participants with T2DM compared with participants without T2DM.ResultsThe mean (SD) age and body mass index (calculated as weight in kilograms divided by the square of the height in meters) were 50.9 (11.5) years and 34.7 (6.3), respectively. The median time between biopsies was 3.3 years (interquartile range, 1.8-6.1 years). Participants with T2DM had a significantly higher cumulative incidence of fibrosis progression at 4 years (24% vs 20%), 8 years (60% vs 50%), and 12 years (93% vs 76%) (P = .005). Using a multivariable Cox proportional hazards model adjusted for multiple confounders, T2DM remained an independent predictor of fibrosis progression (adjusted hazard ratio, 1.69; 95% CI, 1.17-2.43; P = .005). The cumulative incidence of fibrosis regression by ≥1 stage was similar in participants with T2DM compared with participants without T2DM (P = .24).ConclusionsIn this large, multicenter cohort study of well-characterized participants with NAFLD and paired liver biopsies, we found that fibrosis progressed faster in participants with T2DM compared with participants without T2DM. These data have important implications for clinical practice and trial design.
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- 2023
14. A patient-based iPSC-derived hepatocyte model of alcohol-associated cirrhosis reveals bioenergetic insights into disease pathogenesis
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Mukhopadhyay, Bani, Marietta, Cheryl, Shen, Pei-Hong, Oiseni, Abdul, Mirshahi, Faridoddin, Mazzu, Maria, Hodgkinson, Colin, Winkler, Eli, Yuan, Qiaoping, Miranda, Daniel, Kunos, George, Sanyal, Arun J., and Goldman, David
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- 2024
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15. Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial
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Loomba, Rohit, Abdelmalek, Manal F, Armstrong, Matthew J, Jara, Maximilian, Kjær, Mette Skalshøi, Krarup, Niels, Lawitz, Eric, Ratziu, Vlad, Sanyal, Arun J, Schattenberg, Jörn M, Newsome, Philip N, and investigators, NN9931-4492
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Clinical Research ,Diabetes ,Liver Disease ,Clinical Trials and Supportive Activities ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adult ,Humans ,Male ,Female ,Middle Aged ,Diabetes Mellitus ,Type 2 ,Non-alcoholic Fatty Liver Disease ,Glucagon-Like Peptide 1 ,Liver Cirrhosis ,NN9931-4492 investigators ,Clinical sciences - Abstract
BackgroundPatients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis.MethodsThis double-blind, placebo-controlled phase 2 trial enrolled patients from 38 centres in Europe and the USA. Adults with biopsy-confirmed NASH-related cirrhosis and body-mass index (BMI) of 27 kg/m2 or more were randomly assigned (2:1) to receive either once-weekly subcutaneous semaglutide 2·4 mg or visually matching placebo. Patients were randomly allocated via an interactive web response system, stratified by presence or absence of type 2 diabetes. Patients, investigators, and those assessing outcomes were masked to treatment assignment. The primary endpoint was the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH after 48 weeks, assessed by biopsy in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug. The trial is closed and completed, and registered with ClinicalTrials.gov, number NCT03987451.Findings71 patients were enrolled between June 18, 2019, and April 22, 2021; 49 (69%) patients were female and 22 (31%) were male. Patients had a mean age of 59·5 years (SD 8·0) and mean BMI of 34·9 kg/m2 (SD 5·9); 53 (75%) patients had diabetes. 47 patients were randomly assigned to the semaglutide group and 24 to the placebo group. After 48 weeks, there was no statistically significant difference between the two groups in the proportion of patients with an improvement in liver fibrosis of one stage or more without worsening of NASH (five [11%] of 47 patients in the semaglutide group vs seven [29%] of 24 in the placebo group; odds ratio 0·28 [95% CI 0·06-1·24; p=0·087). There was also no significant difference between groups in the proportion of patients who achieved NASH resolution (p=0·29). Similar proportions of patients in each group reported adverse events (42 [89%] patients in the semaglutide group vs 19 [79%] in the placebo group) and serious adverse events (six [13%] vs two [8%]). The most common adverse events were nausea (21 [45%] vs four [17%]), diarrhoea (nine [19%] vs two [8%]), and vomiting (eight [17%] vs none). Hepatic and renal function remained stable. There were no decompensating events or deaths.InterpretationIn patients with NASH and compensated cirrhosis, semaglutide did not significantly improve fibrosis or achievement of NASH resolution versus placebo. No new safety concerns were raised.FundingNovo Nordisk A/S.
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- 2023
16. 334 HEPATIC RETICULOENDOTHELIAL SYSTEM CELL IRON DEPOSITION IS INDEPENDENTLY ASSOCIATED WITH ADVANCED FIBROSIS IN NASH: ANALYSIS OF 2833 PATIENTS FROM THE NASH-CRN
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Sohal, Aalam, Wilson, Laura, Loomba, Rohit, Dasarathy, Srinivasan, Sanyal, Arun J, Chalasani, Naga P, Diehl, Anna Mae, and Kowdley, Kris V
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Biomedical and Clinical Sciences ,Clinical Sciences ,Nutrition and Dietetics ,Neurosciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology ,Clinical sciences ,Nutrition and dietetics - Published
- 2023
17. Defining the serum proteomic signature of hepatic steatosis, inflammation, ballooning and fibrosis in non-alcoholic fatty liver disease
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Sanyal, Arun J, Williams, Stephen A, Lavine, Joel E, Neuschwander-Tetri, Brent A, Alexander, Leigh, Ostroff, Rachel, Biegel, Hannah, Kowdley, Kris V, Chalasani, Naga, Dasarathy, Srinivasan, Diehl, Anna Mae, Loomba, Rohit, Hameed, Bilal, Behling, Cynthia, Kleiner, David E, Karpen, Saul J, Williams, Jessica, Jia, Yi, Yates, Katherine P, and Tonascia, James
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Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Hepatitis ,Nutrition ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Digestive Diseases ,Clinical Research ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Good Health and Well Being ,Humans ,Biopsy ,Fibrosis ,Inflammation ,Liver ,Liver Cirrhosis ,Non-alcoholic Fatty Liver Disease ,Pioglitazone ,Proteomics ,Vitamin E ,Nonalcoholic fatty liver disease ,Nonalcoholic steatohepatitis ,NAFLD activity score ,fibrosis stage ,cirrhosis ,stea-tohepatitis ,steatosis ,hepatocellular ballooning ,lobular inflammation ,fibrosis ,proteomics ,aptamers ,steatohepatitis ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsDespite recent progress, non-invasive tests for the diagnostic assessment and monitoring of non-alcoholic fatty liver disease (NAFLD) remain an unmet need. Herein, we aimed to identify diagnostic signatures of the key histological features of NAFLD.MethodsUsing modified-aptamer proteomics, we assayed 5,220 proteins in each of 2,852 single serum samples from 636 individuals with histologically confirmed NAFLD. We developed and validated dichotomized protein-phenotype models to identify clinically relevant severities of steatosis (grade 0 vs. 1-3), hepatocellular ballooning (0 vs. 1 or 2), lobular inflammation (0-1 vs. 2-3) and fibrosis (stages 0-1 vs. 2-4).ResultsThe AUCs of the four protein models, based on 37 analytes (18 not previously linked to NAFLD), for the diagnosis of their respective components (at a clinically relevant severity) in training/paired validation sets were: fibrosis (AUC 0.92/0.85); steatosis (AUC 0.95/0.79), inflammation (AUC 0.83/0.72), and ballooning (AUC 0.87/0.83). An additional outcome, at-risk NASH, defined as steatohepatitis with NAFLD activity score ≥4 (with a score of at least 1 for each of its components) and fibrosis stage ≥2, was predicted by multiplying the outputs of each individual component model (AUC 0.93/0.85). We further evaluated their ability to detect change in histology following treatment with placebo, pioglitazone, vitamin E or obeticholic acid. Component model scores significantly improved in the active therapies vs. placebo, and differential effects of vitamin E, pioglitazone, and obeticholic acid were identified.ConclusionsSerum protein scanning identified signatures corresponding to the key components of liver biopsy in NAFLD. The models developed were sufficiently sensitive to characterize the longitudinal change for three different drug interventions. These data support continued validation of these proteomic models to enable a "liquid biopsy"-based assessment of NAFLD.Clinical trial numberNot applicable.Impact and implicationsAn aptamer-based protein scan of serum proteins was performed to identify diagnostic signatures of the key histological features of non-alcoholic fatty liver disease (NAFLD), for which no approved non-invasive diagnostic tools are currently available. We also identified specific protein signatures related to the presence and severity of NAFLD and its histological components that were also sensitive to change over time. These are fundamental initial steps in establishing a serum proteome-based diagnostic signature of NASH and provide the rationale for using these signatures to test treatment response and to identify several novel targets for evaluation in the pathogenesis of NAFLD.
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- 2023
18. Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial
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Brown, Elizabeth A, Minnich, Anne, Sanyal, Arun J, Loomba, Rohit, Du, Shuyan, Schwarz, John, Ehman, Richard L, Karsdal, Morten, Leeming, Diana J, Cizza, Giovanni, and Charles, Edgar D
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Clinical Research ,Hepatitis ,Clinical Trials and Supportive Activities ,4.1 Discovery and preclinical testing of markers and technologies ,4.2 Evaluation of markers and technologies ,Detection ,screening and diagnosis ,Oral and gastrointestinal ,Cancer ,Good Health and Well Being ,fibroblast growth factor 21 ,non-alcoholic steatohepatitis ,liver fibrosis ,steatosis ,precirrhotic NASH ,SomaSignal ,ALT ,alanine aminotransferase ,APRI ,AST-to-platelet ratio index ,AST ,aspartate aminotransferase ,CK-18 M30 ,caspase-cleaved cytokeratin 18 ,ELF ,enhanced liver fibrosis ,FGF21 ,fibroblast growth factor 21 ,FIB-4 ,fibrosis-4 index ,MRE ,magnetic resonance elastography ,MRI-PDFF ,MRI-proton density fat fraction ,NAFLD ,non-alcoholic fatty liver disease ,NAS ,NAFLD activity score ,NASH ,non-alcoholic steatohepatitis ,P3NP ,procollagen-3 N-terminal propeptide ,PC3X ,crosslinked ADAMTS-2-released N-terminal type III collagen propeptide ,PGBF ,pegbelfermin ,PRO-C3 ,monomeric ADAMTS-2-released N-terminal type III collagen propeptide ,T2D ,type 2 diabetes ,TG ,triglycerides ,TIMP-1 ,tissue inhibitor of metalloproteinases type 1 ,Clinical sciences - Abstract
Background & aimsFALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 post hoc analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers.MethodsBlood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1 at baseline through week 24. SomaSignal tests assessed protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood. Linear mixed-effect models were fit for each biomarker. Correlations and concordance were assessed between blood-based biomarkers, imaging, and histological metrics.ResultsAt week 24, pegbelfermin significantly improved blood-based composite fibrosis scores (ELF, FIB-4, APRI), fibrogenesis biomarkers (PRO-C3 and PC3X), adiponectin, CK-18, hepatic fat fraction measured by MRI-proton density fat fraction, and all four SomaSignal NASH component tests. Correlation analyses between histological and non-invasive measures identified four main categories: steatosis/metabolism, tissue injury, fibrosis, and biopsy-based metrics. Concordant and discordant effects of pegbelfermin on the primary endpoint vs. biomarker responses were observed; the most clear and concordant effects were on measures of liver steatosis and metabolism. A significant association between hepatic fat measured histologically and by imaging was observed in pegbelfermin arms.ConclusionsPegbelfermin improved NASH-related biomarkers most consistently through improvement of liver steatosis, though biomarkers of tissue injury/inflammation and fibrosis were also improved. Concordance analysis shows that non-invasive assessments of NASH support and exceed the improvements detected by liver biopsy, suggesting that greater consideration should be given to the totality of available data when evaluating the efficacy of NASH therapeutics.Clinical trial numberPost hoc analysis of NCT03486899.Impact and implicationsFALCON 1 was a study of pegbelfermin vs. placebo in patients with non-alcoholic steatohepatitis (NASH) without cirrhosis; in this study, patients who responded to pegbelfermin treatment were identified through examination of liver fibrosis in tissue samples collected through biopsy. In the current analysis, non-invasive blood- and imaging-based measures of fibrosis, liver fat, and liver injury were used to determine pegbelfermin treatment response to see how they compared with the biopsy-based results. We found that many of the non-invasive tests, particularly those that measured liver fat, identified patients who responded to pegbelfermin treatment, consistent with the liver biopsy findings. These results suggest that there may be additional value in using data from non-invasive tests, along with liver biopsy, to evaluate how well patients with NASH respond to treatment.
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- 2023
19. Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis
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Loomba, Rohit, Huang, Daniel Q, Sanyal, Arun J, Anstee, Quentin Mark, Trauner, Michael, Lawitz, Eric J, Ding, Dora, Ma, Lily, Jia, Catherine, Billin, Andrew, Huss, Ryan S, Chung, Chuhan, Goodman, Zachary, Wong, Vincent Wai-Sun, Okanoue, Takeshi, Romero-Gómez, Manuel, Abdelmalek, Manal F, Muir, Andrew, Afdhal, Nezam, Bosch, Jaime, Harrison, Stephen, Younossi, Zobair M, and Myers, Robert P
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Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Liver Disease ,Clinical Research ,Clinical Trials and Supportive Activities ,Hepatitis ,Oral and gastrointestinal ,Good Health and Well Being ,Humans ,Non-alcoholic Fatty Liver Disease ,Prospective Studies ,Retrospective Studies ,Liver Cirrhosis ,Liver ,Elasticity Imaging Techniques ,Disease Progression ,cirrhosis ,fibrosis ,nonalcoholic steatohepatitis ,Clinical Sciences ,Paediatrics and Reproductive Medicine ,Gastroenterology & Hepatology - Abstract
ObjectiveIn retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed cohorts with advanced fibrosis are limited. We aimed to establish thresholds for LS by VCTE that predict progression to cirrhosis among patients with bridging fibrosis and hepatic decompensation among patients with cirrhosis due to NASH.DesignWe used data from four randomised placebo-controlled trials of selonsertib and simtuzumab in participants with advanced fibrosis (F3-F4). The trials were discontinued due to lack of efficacy. Liver fibrosis was staged centrally at baseline and week 48 (selonsertib study) or week 96 (simtuzumab study). Associations between LS by VCTE with disease progression were determined using Cox proportional hazards regression analysis.ResultsProgression to cirrhosis occurred in 16% (103/664) of participants with bridging fibrosis and adjudicated liver-related events occurred in 4% (27/734) of participants with baseline cirrhosis. The optimal baseline LS thresholds were ≥16.6 kPa for predicting progression to cirrhosis, and ≥30.7 kPa for predicting liver-related events. Baseline LS ≥16.6 kPa (adjusted HR 3.99; 95% CI 2.66 to 5.98, p
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- 2023
20. Changes in abdominal adipose tissue depots assessed by MRI correlate with hepatic histologic improvement in non-alcoholic steatohepatitis
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Shen, Wei, Middleton, Michael S, Cunha, Guilherme M, Delgado, Timoteo I, Wolfson, Tanya, Gamst, Anthony, Fowler, Kathryn J, Alazraki, Adina, Trout, Andrew T, Ohliger, Michael A, Shah, Shetal N, Bashir, Mustafa R, Kleiner, David E, Loomba, Rohit, Neuschwander-Tetri, Brent A, Sanyal, Arun J, Zhou, Jane, Sirlin, Claude B, and Lavine, Joel E
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Biomedical and Clinical Sciences ,Clinical Sciences ,Prevention ,Chronic Liver Disease and Cirrhosis ,Clinical Research ,Nutrition ,Liver Disease ,Clinical Trials and Supportive Activities ,Obesity ,Hepatitis ,Digestive Diseases ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Cardiovascular ,Cancer ,Oral and gastrointestinal ,Adult ,Humans ,Non-alcoholic Fatty Liver Disease ,Obesity ,Abdominal ,Liver ,Fibrosis ,Abdominal Fat ,Magnetic Resonance Imaging ,Adipose Tissue ,central obesity ,deep subcutaneous adipose tissue ,visceral adipose tissue ,liver histology ,Public Health and Health Services ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Background & aimsNon-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement.MethodsAdult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI.ResultsTreatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively).ConclusionsIn adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF.Clinical trial numberNCT01265498.Impact and implicationsAlthough central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.
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- 2023
21. Digital pathology for nonalcoholic steatohepatitis assessment
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Sanyal, Arun J., Jha, Prakash, and Kleiner, David E.
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- 2024
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22. TOPLINE RESULTS FROM A NEW ANALYSIS OF THE REGENERATE TRIAL OF OBETICHOLIC ACID FOR THE TREATMENT OF NONALCOHOLIC STEATOHEPATITIS
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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
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Medical Biochemistry and Metabolomics ,Clinical Sciences ,Immunology ,Gastroenterology & Hepatology ,Clinical sciences - Published
- 2023
23. Contributors
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Acharya, Shamasunder, primary, Arumugam, Somasundaram, additional, Bagchi, Manashi, additional, Bagchi, Debasis, additional, Bala, Sapna, additional, Balakrishnan, Grrishma, additional, Bandopadhyay, Purbita, additional, Bandyopadhyay, Arun, additional, Banerjee, Mainak, additional, Banik, Samudra P., additional, Bhadada, Sanjay Kumar, additional, Bhat, Sowrabha, additional, Bhatnagar, Apoorva, additional, Bhowmik, Eshita, additional, Bir, Aritri, additional, Biswas, Subhash Ch., additional, Brodosi, Lucia, additional, Burrage, Lauren, additional, Buttari, Brigitta, additional, Chakrabarti, Sankha Shubhra, additional, Chakrabarti, Partha, additional, Chakrabarti, Sasanka, additional, Chakraborty, Sanjoy, additional, Chatterjee, Aroup, additional, Chatterjee, Sudip, additional, Chattopadhyay, Dipanjan, additional, Chaudhury, Tirthankar, additional, Cherian, Kripa Elizabeth, additional, Chowdhury, Amarta Shankar, additional, Dabadghao, Preeti, additional, Dabas, Aashima, additional, Das, Snehasis, additional, Das, Pamelika, additional, Das, Jishna, additional, Dasgupta, Riddhi, additional, Dasgupta, I., additional, Dissanayake, H.A., additional, Downs, Bernard W., additional, Dutta, Deep, additional, Duttaroy, Asim K., additional, Fariduddin, Maria M., additional, Fazeli, Mostafa, additional, Ferns, Gordon A., additional, Ferrari, Carlos K.B., additional, Gangopadhyay, Kalyan Kumar, additional, Ganguly, Dipyaman, additional, Ganguly, Anirban, additional, Ganie, Mohd Ashraf, additional, Garg, M.K., additional, Gargari, Piyas, additional, Geer, Mohammad Ishaq, additional, Ghayour-Mobarhan, Majid, additional, Ghosh, Amrit Raj, additional, Ghosh, Arindam, additional, Ghosh, Rituparna, additional, Goswami, Soumik, additional, Grover, B., additional, Gupta, Sudhiranjan, additional, Haldipur, Ashrita C., additional, Hayer, M.K., additional, Heller, Simon, additional, Iqbal, Ahmed, additional, Jacob, Jubbin J., additional, Jebasingh, Felix, additional, Jude, Edward B., additional, Kanumilli, Naresh, additional, Kapoor, Nitin, additional, Kettler, Zelpha K., additional, Khoo, C.M., additional, Krishnaveni, G.V., additional, Kumar, Sandeep, additional, Kumar, Angad, additional, Kushner, Steve, additional, Lee, K.O., additional, Li, Dong, additional, Li, Li, additional, Maisnam, Indira, additional, Majumdar, Sujoy, additional, Majumder, Anirban, additional, Marchesini, Giulio, additional, Marwaha, Raman Kumar, additional, Mirshad, Reshma, additional, Misra, A., additional, Mitra, Sandip Kumar, additional, Mittal, Madhukar, additional, Mohan, Viswanathan, additional, Mondal, Sunetra, additional, Müller, Walter E., additional, Mukherjee, Sutapa, additional, Mukherjee, J.J., additional, Mukhopadhyay, Rajarshi, additional, Mukhopadhyay, Satinath, additional, Muthiah, Mark, additional, Naik, Ramachandra G., additional, Pal, Rimesh, additional, Palui, Rajan, additional, Paul, Thomas V., additional, Petroni, Maria Letizia, additional, Prasanna, Vani Sai, additional, Preuss, Harry G., additional, Profumo, Elisabetta, additional, Puppala, Alekhya, additional, Rankawat, Sourbh, additional, Rasool, Abid, additional, Ray, Aleepta Guha, additional, Ray, Sayantan, additional, Ray, Sandipan, additional, Raychaudhuri, Smriti K., additional, Raychaudhuri, Siba P., additional, Roy, Trina, additional, Saberi-Karimian, Maryam, additional, Safarian-Bana, Hamideh, additional, Saha, Arpita, additional, Saha, Sarmistha, additional, Sahar, Tajali, additional, Sahoo, J.P., additional, Saikia, Uma Kaimal, additional, Sanjeevi, Carani B., additional, Sanyal, Arun J., additional, Sarkar, Jit, additional, Sarkar, Sulogna, additional, Saso, Luciano, additional, Satpathi, Tirthankar, additional, Sharif, Adnan, additional, Shetty, Shrinath Pratap, additional, Singh, Awadhesh Kumar, additional, Singh, Ritu, additional, Sinha, Ashim, additional, Somasundaram, N.P., additional, Sreedhar, Remya, additional, Srividya, N., additional, Tabatabaeizadeh, Seyed-Amir, additional, Tan, Eunice Xiang Xuan, additional, Thomas, Nihal, additional, Unnikrishnan, Ranjit, additional, Velayutham, Ravichandiran, additional, Vella, Adrian, additional, Viswanathan, Vijay, additional, Vora, Jiten, additional, Wagle, S.S., additional, Welch, Andrew, additional, Yajnik, C.S., additional, Yellurkar, Manoj Limbraj, additional, Yousuf, Syed Douhath, additional, and Zhang, Jian, additional
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- 2024
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24. Pharmacologic therapies in metabolic syndrome with special reference to non-alcoholic fatty liver disease
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Sanyal, Arun J., primary, Muthiah, Mark, additional, and Tan, Eunice Xiang Xuan, additional
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- 2024
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25. Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD
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Gawrieh, Samer, Vilar-Gomez, Eduardo, Wilson, Laura A., Pike, Francis, Kleiner, David E., Neuschwander-Tetri, Brent A., Diehl, Anna Mae, Dasarathy, Srinivasan, Kowdley, Kris V., Hameed, Bilal, Tonascia, James, Loomba, Rohit, Sanyal, Arun J., and Chalasani, Naga
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- 2024
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26. Safety and Efficacy of Novel Incretin Co-agonist Cotadutide in Biopsy-proven Noncirrhotic MASH With Fibrosis
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Shankar, Sudha S., Daniels, Samuel J., Robertson, Darren, Sarv, Janeli, Sánchez, José, Carter, Debra, Jermutus, Lutz, Challis, Benjamin, and Sanyal, Arun J.
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- 2024
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27. Diagnostic performance of circulating biomarkers for non-alcoholic steatohepatitis
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Sanyal, Arun J., Shankar, Sudha S., Yates, Katherine P., Bolognese, James, Daly, Erika, Dehn, Clayton A., Neuschwander-Tetri, Brent, Kowdley, Kris, Vuppalanchi, Raj, Behling, Cynthia, Tonascia, James, Samir, Anthony, Sirlin, Claude, Sherlock, Sarah P., Fowler, Kathryn, Heymann, Helen, Kamphaus, Tania N., Loomba, Rohit, and Calle, Roberto A.
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- 2023
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28. Differential fuel utilization in liver transplant recipients and its relationship with non‐alcoholic fatty liver disease
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Siddiqui, Mohammad S, Patel, Samarth, Forsgren, Mikael, Bui, Anh T, Shen, Steve, Syed, Taseen, Boyett, Sherry, Chen, Shanshan, Sanyal, Arun J, Wolver, Susan, Kirkman, Danielle, Celi, Francesco S, and Bhati, Chandra S
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Hepatitis ,Chronic Liver Disease and Cirrhosis ,Obesity ,Transplantation ,Prevention ,Nutrition ,Digestive Diseases ,Oral and gastrointestinal ,Metabolic and endocrine ,Carbohydrates ,Humans ,Liver Cirrhosis ,Liver Transplantation ,Non-alcoholic Fatty Liver Disease ,carbohydrates ,energy expenditure ,fatty acids ,liver transplantation ,metabolic flexibility ,non-alcoholic steatohepatitis ,Gastroenterology & Hepatology ,Clinical sciences - Abstract
Metabolic flexibility is the ability to match biofuel availability to utilization. Reduced metabolic flexibility, or lower fatty acid (FA) oxidation in the fasted state, is associated with obesity. The present study evaluated metabolic flexibility after liver transplantation (LT).MethodsPatients receiving LT for non-alcoholic steatohepatitis (NASH) (n = 35) and non-NASH (n = 10) were enrolled. NASH was chosen as these patients are at the highest risk of metabolic complications. Metabolic flexibility was measured using whole-body calorimetry and expressed as respiratory quotient (RQ), which ranges from 0.7 (pure FA oxidation) to 1.0 is (carbohydrate oxidation).ResultsThe two cohorts were similar except for a higher prevalence of obesity and diabetes in the NASH cohort. Post-prandially, RQ increased in both cohorts (i.e. greater carbohydrate utilization) but peak RQ and time at peak RQ was higher in the NASH cohort. Fasting RQ in NASH was significantly higher (0.845 vs. 0.772, p
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- 2022
29. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation
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Vujkovic, Marijana, Ramdas, Shweta, Lorenz, Kim M, Guo, Xiuqing, Darlay, Rebecca, Cordell, Heather J, He, Jing, Gindin, Yevgeniy, Chung, Chuhan, Myers, Robert P, Schneider, Carolin V, Park, Joseph, Lee, Kyung Min, Serper, Marina, Carr, Rotonya M, Kaplan, David E, Haas, Mary E, MacLean, Matthew T, Witschey, Walter R, Zhu, Xiang, Tcheandjieu, Catherine, Kember, Rachel L, Kranzler, Henry R, Verma, Anurag, Giri, Ayush, Klarin, Derek M, Sun, Yan V, Huang, Jie, Huffman, Jennifer E, Creasy, Kate Townsend, Hand, Nicholas J, Liu, Ching-Ti, Long, Michelle T, Yao, Jie, Budoff, Matthew, Tan, Jingyi, Li, Xiaohui, Lin, Henry J, Chen, Yii-Der Ida, Taylor, Kent D, Chang, Ruey-Kang, Krauss, Ronald M, Vilarinho, Silvia, Brancale, Joseph, Nielsen, Jonas B, Locke, Adam E, Jones, Marcus B, Verweij, Niek, Baras, Aris, Reddy, K Rajender, Neuschwander-Tetri, Brent A, Schwimmer, Jeffrey B, Sanyal, Arun J, Chalasani, Naga, Ryan, Kathleen A, Mitchell, Braxton D, Gill, Dipender, Wells, Andrew D, Manduchi, Elisabetta, Saiman, Yedidya, Mahmud, Nadim, Miller, Donald R, Reaven, Peter D, Phillips, Lawrence S, Muralidhar, Sumitra, DuVall, Scott L, Lee, Jennifer S, Assimes, Themistocles L, Pyarajan, Saiju, Cho, Kelly, Edwards, Todd L, Damrauer, Scott M, Wilson, Peter W, Gaziano, J Michael, O’Donnell, Christopher J, Khera, Amit V, Grant, Struan FA, Brown, Christopher D, Tsao, Philip S, Saleheen, Danish, Lotta, Luca A, Bastarache, Lisa, Anstee, Quentin M, Daly, Ann K, Meigs, James B, Rotter, Jerome I, Lynch, Julie A, Rader, Daniel J, Voight, Benjamin F, and Chang, Kyong-Mi
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Genetics ,Liver Disease ,Human Genome ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Aetiology ,2.1 Biological and endogenous factors ,Alanine Transaminase ,Alpha-Ketoglutarate-Dependent Dioxygenase FTO ,Genome-Wide Association Study ,Humans ,Intracellular Signaling Peptides and Proteins ,Lipase ,Membrane Proteins ,Non-alcoholic Fatty Liver Disease ,Polymorphism ,Single Nucleotide ,Protein Serine-Threonine Kinases ,Regeneron Genetics Center ,Geisinger-Regeneron DiscovEHR Collaboration ,EPoS Consortium ,VA Million Veteran Program ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P
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- 2022
30. Comparison of clinical prediction rules for ruling out cirrhosis in nonalcoholic fatty liver disease (NAFLD)
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Brandman, Danielle, Boyle, Marie, McPherson, Stuart, Van Natta, Mark L, Sanyal, Arun J, Kowdley, Kris, Neuschwander‐Tetri, Brent, Chalasani, Naga, Abdelmalek, Manal F, Terrault, Norah A, McCullough, Art, Bettencourt, Ricki, Caussy, Cyrielle, Kleiner, David E, Behling, Cynthia, Tonascia, James, Anstee, Quentin M, Loomba, Rohit, and Network, Members of the Nonalcoholic Steatohepatitis Clinical Research
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Hepatitis ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Oral and gastrointestinal ,Good Health and Well Being ,Adult ,Biopsy ,Clinical Decision Rules ,Cross-Sectional Studies ,Female ,Fibrosis ,Humans ,Liver ,Liver Cirrhosis ,Non-alcoholic Fatty Liver Disease ,cirrhosis ,nonalcoholic fatty liver disease ,noninvasive assessment ,Members of the Nonalcoholic Steatohepatitis Clinical Research Network ,Pharmacology and Pharmaceutical Sciences ,Gastroenterology & Hepatology ,Clinical sciences ,Pharmacology and pharmaceutical sciences - Abstract
Background and aimsPatients with nonalcoholic fatty liver disease (NAFLD) cirrhosis benefit from referral to subspecialty care. While several clinical prediction rules exist to identify advanced fibrosis, the cutoff for excluding cirrhosis due to NAFLD is unclear. This analysis compared clinical prediction rules for excluding biopsy-proven cirrhosis in NAFLD.MethodsAdult patients were enrolled in the NASH Clinical Research Network (US) and the Newcastle Cohort (UK). Clinical and laboratory data were collected at enrolment, and a liver biopsy was taken within 1 year of enrolment. Optimal cutoffs for each score (eg, FIB-4) to exclude cirrhosis were derived from the US cohort, and sensitivity, specificity, positive predictive value, negative predictive value and AUROC were calculated. The cutoffs were evaluated in the UK cohort.Results147/1483 (10%) patients in the US cohort had cirrhosis. All prediction rules had similarly high NPV (0.95-0.97). FIB-4 and NAFLD fibrosis scores were the most accurate in characterising patients as having cirrhosis (AUROC 0.84-0.86). 59/494 (12%) patients in the UK cohort had cirrhosis. Prediction rules had high NPV (0.92-0.96), and FIB-4 and NAFLD fibrosis score the most accurate in the prediction of cirrhosis in the UK cohort (AUROC 0.87-0.89).ConclusionsThis cross-sectional analysis of large, multicentre international datasets shows that current clinical prediction rules perform well in excluding cirrhosis with appropriately chosen cutoffs. These clinical prediction rules can be used in primary care to identify patients, particularly those who are white, female, and
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- 2022
31. Cardiovascular disease in patients with metabolic dysfunction-associated steatohepatitis compared with metabolic dysfunction-associated steatotic liver disease and other liver diseases: A systematic review
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Sanyal, Arun J., Husain, Mansoor, Diab, Crystel, Mangla, Kamal Kant, Shoeb, Ahsan, Lingvay, Ildiko, and Tapper, Elliot B.
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- 2024
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32. Randomized trial of anakinra plus zinc vs. prednisone for severe alcohol-associated hepatitis
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Chalasani, Naga, Patidar, Kavish R., Vuppalanchi, Raj, Samala, Niha, Yoder, Lindsey, Nephew, Lauren, Shah, Vijay H., Simonetto, Douglas A., Kamath, Patrick, Vargas, Hugo E., Yang, Liu, Dasarathy, Srinivasan, Welch, Nicole, Bellar, Annette, Attaway, Amy, Dasarathy, Jaividhya, Growley, Ashley, Streem, David, Nagy, Laura E., Mitchell, Mack C., Herlong, H. Franklin, Kerr, Thomas, Cotter, Thomas, Sanyal, Arun, O'Connor, Sara, Luketic, Velimir, Asgharpour, Amon, Taylor, Stephanie, McClain, Craig J., Vatsalya, Vatsalya, Jophlin, Loretta, Cave, Matt, Jha, Suman Kumar, Marsano, Luis, Barve, Ashutosh, Frimodig, Jane, Bataller, Ramon, Ravi, Samhita, Behari, Jaideep, Shivanekar, Sharvari, Novelli, Paula, Duarte-Rojo, Andres, Jonassaint, Naudia, Szabo, Gyongyi, Curry, Jiang, Zhenghui G., Agarwal, Ushma, Hazel, Mia, Schnabl, Bernd, Gawrieh, Samer, Tu, Wanzhu, Kamath, Patrick S., Chalasani, Naga P., Tang, Qing, Radaeva, Svetlana, Barton, Bruce, and Sanyal, Arun J.
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- 2024
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33. A randomised Phase IIa trial of amine oxidase copper-containing 3 (AOC3) inhibitor BI 1467335 in adults with non-alcoholic steatohepatitis
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Newsome, Philip N., Sanyal, Arun J., Neff, Guy, Schattenberg, Jörn M., Ratziu, Vlad, Ertle, Judith, Link, Jasmin, Mackie, Alison, Schoelch, Corinna, and Lawitz, Eric
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- 2023
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34. The crosstalking immune cells network creates a collective function beyond the function of each cellular constituent during the progression of hepatocellular carcinoma
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Koelsch, Nicholas, Mirshahi, Faridoddin, Aqbi, Hussein F., Saneshaw, Mulugeta, Idowu, Michael O., Olex, Amy L., Sanyal, Arun J., and Manjili, Masoud H.
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- 2023
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35. Clinical characteristics, surveillance, treatment allocation, and outcomes of non-alcoholic fatty liver disease-related hepatocellular carcinoma: a systematic review and meta-analysis
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Tan, Darren Jun Hao, Ng, Cheng Han, Lin, Snow Yunni, Pan, Xin Hui, Tay, Phoebe, Lim, Wen Hui, Teng, Margaret, Syn, Nicholas, Lim, Grace, Yong, Jie Ning, Quek, Jingxuan, Xiao, Jieling, Dan, Yock Young, Siddiqui, Mohammad Shadab, Sanyal, Arun J, Muthiah, Mark D, Loomba, Rohit, and Huang, Daniel Q
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Chronic Liver Disease and Cirrhosis ,Rare Diseases ,Liver Disease ,Digestive Diseases ,Liver Cancer ,Hepatitis ,Cancer ,Good Health and Well Being ,Carcinoma ,Hepatocellular ,Child ,Cross-Sectional Studies ,Humans ,Liver Cirrhosis ,Liver Neoplasms ,Non-alcoholic Fatty Liver Disease ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
BackgroundThe clinical presentation and outcomes of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma are unclear when compared with hepatocellular carcinoma due to other causes. We aimed to establish the prevalence, clinical features, surveillance rates, treatment allocation, and outcomes of NAFLD-related hepatocellular carcinoma.MethodsIn this systematic review and meta-analysis, we searched MEDLINE and Embase from inception until Jan 17, 2022, for articles in English that compared clinical features, and outcomes of NAFLD-related hepatocellular carcinoma versus hepatocellular carcinoma due to other causes. We included cross-sectional and longitudinal observational studies and excluded paediatric studies. Study-level data were extracted from the published reports. The primary outcomes were (1) the proportion of hepatocellular carcinoma secondary to NAFLD, (2) comparison of patient and tumour characteristics of NAFLD-related hepatocellular carcinoma versus other causes, and (3) comparison of surveillance, treatment allocation, and overall and disease-free survival outcomes of NAFLD-related versus non-NAFLD-related hepatocellular carcinoma. We analysed proportional data using a generalised linear mixed model. Pairwise meta-analysis was done to obtain odds ratio (OR) or mean difference, comparing NAFLD-related with non-NAFLD-related hepatocellular carcinoma. We evaluated survival outcomes using pooled analysis of hazard ratios.FindingsOf 3631 records identified, 61 studies (done between January, 1980, and May, 2021; 94 636 patients) met inclusion criteria. Overall, the proportion of hepatocellular carcinoma cases secondary to NAFLD was 15·1% (95% CI 11·9-18·9). Patients with NAFLD-related hepatocellular carcinoma were older (p75%), and all articles had low-to-moderate risk of bias.InterpretationNAFLD-related hepatocellular carcinoma is associated with a higher proportion of patients without cirrhosis and lower surveillance rates than hepatocellular carcinoma due to other causes. Surveillance strategies should be developed for patients with NAFLD without cirrhosis who are at high risk of developing hepatocellular carcinoma.FundingNone.
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- 2022
36. Impact of age on NIS2+™ and other non-invasive blood tests for the evaluation of liver disease and detection of at-risk MASH
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Anstee, Quentin M., Magnanensi, Jeremy, Hajji, Yacine, Caron, Alexandra, Majd, Zouher, Rosenquist, Christian, Hum, Dean W., Staels, Bart, Connelly, Margery A., Loomba, Rohit, Harrison, Stephen A., Ratziu, Vlad, and Sanyal, Arun J.
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- 2024
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37. Emerging therapies for MASLD and their impact on plasma lipids
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Nguyen, Madison, Asgharpour, Amon, Dixon, Dave L., Sanyal, Arun J., and Mehta, Anurag
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- 2024
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38. NIS2+TM as a screening tool to optimize patient selection in metabolic dysfunction-associated steatohepatitis clinical trials
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Ratziu, Vlad, Harrison, Stephen A., Hajji, Yacine, Magnanensi, Jeremy, Petit, Stephanie, Majd, Zouher, Delecroix, Elodie, Rosenquist, Christian, Hum, Dean, Staels, Bart, Anstee, Quentin M., and Sanyal, Arun J.
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- 2024
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39. Artificial intelligence-assisted digital pathology for non-alcoholic steatohepatitis: current status and future directions
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Ratziu, Vlad, Hompesch, Marcus, Petitjean, Mathieu, Serdjebi, Cindy, Iyer, Janani S., Parwani, Anil V., Tai, Dean, Bugianesi, Elisabetta, Cusi, Kenneth, Friedman, Scott L., Lawitz, Eric, Romero-Gómez, Manuel, Schuppan, Detlef, Loomba, Rohit, Paradis, Valérie, Behling, Cynthia, and Sanyal, Arun J.
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- 2024
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40. Validation of the accuracy of the FAST™ score for detecting patients with at-risk nonalcoholic steatohepatitis (NASH) in a North American cohort and comparison to other non-invasive algorithms
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Woreta, Tinsay A, Van Natta, Mark L, Lazo, Mariana, Krishnan, Arunkumar, Neuschwander-Tetri, Brent A, Loomba, Rohit, Diehl, Anna Mae, Abdelmalek, Manal F, Chalasani, Naga, Gawrieh, Samer, Dasarathy, Srinivasan, Vuppalanchi, Raj, Siddiqui, Mohammad S, Kowdley, Kris V, McCullough, Arthur, Terrault, Norah A, Behling, Cynthia, Kleiner, David E, Fishbein, Mark, Hertel, Paula, Wilson, Laura A, Mitchell, Emily P, Miriel, Laura A, Clark, Jeanne M, Tonascia, James, and Sanyal, Arun J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Digestive Diseases ,Liver Disease ,Chronic Liver Disease and Cirrhosis ,Women's Health ,Obesity ,Hepatitis ,Clinical Research ,4.2 Evaluation of markers and technologies ,Oral and gastrointestinal ,Adult ,Algorithms ,Biopsy ,Cohort Studies ,Female ,Fibrosis ,Humans ,Liver ,Liver Cirrhosis ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Severity of Illness Index ,NASH Clinical Research Network ,General Science & Technology - Abstract
Background and aimsManagement of patients with NASH who are at elevated risk of progressing to complications of cirrhosis (at-risk NASH) would be enhanced by an accurate, noninvasive diagnostic test. The new FAST™ score, a combination of FibroScan® parameters liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) and aspartate aminotransferase (AST), has shown good diagnostic accuracy for at-risk NASH (area-under-the-Receiver-Operating-Characteristic [AUROC] = 0.80) in European cohorts. We aimed to validate the FAST™ score in a North American cohort and show how its diagnostic accuracy might vary by patient mix. We also compared the diagnostic performance of FAST™ to other non-invasive algorithms for the diagnosis of at-risk NASH.MethodsWe studied adults with biopsy-proven non-alcoholic fatty liver disease (NAFLD) from the multicenter NASH Clinical Research Network (CRN) Adult Database 2 (DB2) cohort study. At-risk-NASH was histologically defined as definite NASH with a NAFLD Activity Score (NAS) ≥ 4 with at least 1 point in each category and a fibrosis stage ≥ 2. We used the Echosens® formula for FAST™ from LSM (kPa), CAP (dB/m), and AST (U/L), and the FAST™-based Rule-Out (FAST™ ≤ 0.35, sensitivity = 90%) and Rule-In (FAST™ ≥ 0.67, specificity = 90%) zones. We determined the following diagnostic performance measures: AUROC, sensitivity (Se), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV); these were calculated for the total sample and by subgroups of patients and by FibroScan® exam features. We also compared the at-risk NASH diagnostic performance of FAST™ to other non-invasive algorithms: NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, and AST to platelet ratio index (APRI).ResultsThe NASH CRN population of 585 patients was 62% female, 79% white, 14% Hispanic, and 73% obese; the mean age was 51 years. The mean (SD) AST and ALT were 50 (37) U/L and 66 (45) U/L, respectively. 214 (37%) had at-risk NASH. The AUROC of FAST™ for at-risk NASH in the NASH CRN study population was 0.81 (95% CI: 0.77, 0.84. Using FAST™-based cut-offs, 35% of patients were ruled-out with corresponding NPV = 0.90 and 27% of patients were ruled-in with corresponding PPV = 0.69. The diagnostic accuracy of FAST™ was higher in non-whites vs. whites (AUROC: 0.91 vs 0.78; p = 0.001), and in patients with a normal BMI vs. BMI > 35 kg/m2 (AUROC: 0.94 vs 0.78, p = 0.008). No differences were observed by other patient characteristics or FibroScan® exam features. The FAST™ score had higher diagnostic accuracy than other non-invasive algorithms for the diagnosis of at-risk NASH (AUROC for NFS, FIB-4, and APRI 0.67, 0.73, 0.74, respectively).ConclusionWe validated the FAST™ score for the diagnosis of at-risk NASH in a large, multi-racial population in North America, with a prevalence of at-risk NASH of 37%. Diagnostic performance varies by subgroups of NASH patients defined by race and obesity. FAST™ performed better than other non-invasive algorithms for the diagnosis of at-risk NASH.
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- 2022
41. Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease
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Sanyal, Arun J, Van Natta, Mark L, Clark, Jeanne, Neuschwander-Tetri, Brent A, Diehl, AnnaMae, Dasarathy, Srinivasan, Loomba, Rohit, Chalasani, Naga, Kowdley, Kris, Hameed, Bilal, Wilson, Laura A, Yates, Katherine P, Belt, Patricia, Lazo, Mariana, Kleiner, David E, Behling, Cynthia, and Tonascia, James
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Chronic Liver Disease and Cirrhosis ,Clinical Research ,Liver Disease ,Digestive Diseases ,Good Health and Well Being ,Adult ,Biopsy ,Carcinoma ,Hepatocellular ,Female ,Gastrointestinal Hemorrhage ,Humans ,Incidence ,Liver ,Liver Cirrhosis ,Liver Neoplasms ,Male ,Middle Aged ,Non-alcoholic Fatty Liver Disease ,Prognosis ,Prospective Studies ,Severity of Illness Index ,NASH Clinical Research Network ,Medical and Health Sciences ,General & Internal Medicine - Abstract
BackgroundThe prognoses with respect to mortality and hepatic and nonhepatic outcomes across the histologic spectrum of nonalcoholic fatty liver disease (NAFLD) are not well defined.MethodsWe prospectively followed a multicenter patient population that included the full histologic spectrum of NAFLD. The incidences of death and other outcomes were compared across baseline histologic characteristics.ResultsA total of 1773 adults with NAFLD were followed for a median of 4 years. All-cause mortality increased with increasing fibrosis stages (0.32 deaths per 100 person-years for stage F0 to F2 [no, mild, or moderate fibrosis], 0.89 deaths per 100 persons-years for stage F3 [bridging fibrosis], and 1.76 deaths per 100 person-years for stage F4 [cirrhosis]). The incidence of liver-related complications per 100 person-years increased with fibrosis stage (F0 to F2 vs. F3 vs. F4) as follows: variceal hemorrhage (0.00 vs. 0.06 vs. 0.70), ascites (0.04 vs. 0.52 vs. 1.20), encephalopathy (0.02 vs. 0.75 vs. 2.39), and hepatocellular cancer (0.04 vs. 0.34 vs. 0.14). As compared with patients with stage F0 to F2 fibrosis, patients with stage F4 fibrosis also had a higher incidence of type 2 diabetes (7.53 vs. 4.45 events per 100 person-years) and a decrease of more than 40% in the estimated glomerular filtration rate (2.98 vs. 0.97 events per 100 person-years). The incidence of cardiac events and nonhepatic cancers were similar across fibrosis stages. After adjustment for age, sex, race, diabetes status, and baseline histologic severity, the incidence of any hepatic decompensation event (variceal hemorrhage, ascites, or encephalopathy) was associated with increased all-cause mortality (adjusted hazard ratio, 6.8; 95% confidence interval, 2.2 to 21.3).ConclusionsIn this prospective study involving patients with NAFLD, fibrosis stages F3 and F4 were associated with increased risks of liver-related complications and death. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; NAFLD DB2 ClinicalTrials.gov number, NCT01030484.).
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- 2021
42. Expert Panel Recommendations: Practical Clinical Applications for Initiating and Monitoring Resmetirom in Patients with MASH/NASH and Moderate to Noncirrhotic Advanced Fibrosis
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Noureddin, Mazen, Charlton, Michael R., Harrison, Stephen A., Bansal, Meena B., Alkhouri, Naim, Loomba, Rohit, Sanyal, Arun J., and Rinella, Mary E.
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- 2024
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43. Efficacy, tolerability and pharmacokinetics of survodutide, a glucagon/glucagon-like peptide-1 receptor dual agonist, in cirrhosis
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Lawitz, Eric J., Fraessdorf, Mandy, Neff, Guy W., Schattenberg, Jörn M., Noureddin, Mazen, Alkhouri, Naim, Schmid, Bernhard, Andrews, Charles P., Takács, István, Hussain, Samina Ajaz, Fenske, Wiebke K., Gane, Edward J., Hosseini-Tabatabaei, Azadeh, Sanyal, Arun J., Mazo, Daniel F., and Younes, Ramy
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- 2024
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44. A multisociety Delphi consensus statement on new fatty liver disease nomenclature
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Rinella, Mary E., Lazarus, Jeffrey V., Ratziu, Vlad, Francque, Sven M., Sanyal, Arun J., Kanwal, Fasiha, Romero, Diana, Abdelmalek, Manal F., Anstee, Quentin M., Arab, Juan Pablo, Arrese, Marco, Bataller, Ramon, Beuers, Ulrich, Boursier, Jerome, Bugianesi, Elisabetta, Byrne, Christopher D., Narro, Graciela E. Castro, Chowdhury, Abhijit, Cortez-Pinto, Helena, Cryer, Donna R., Cusi, Kenneth, El-Kassas, Mohamed, Klein, Samuel, Eskridge, Wayne, Fan, Jiangao, Gawrieh, Samer, Guy, Cynthia D., Harrison, Stephen A., Kim, Seung Up, Koot, Bart G., Korenjak, Marko, Kowdley, Kris V., Lacaille, Florence, Loomba, Rohit, Mitchell-Thain, Robert, Morgan, Timothy R., Powell, Elisabeth E., Roden, Michael, Romero-Gómez, Manuel, Silva, Marcelo, Singh, Shivaram Prasad, Sookoian, Silvia C., Spearman, C. Wendy, Tiniakos, Dina, Valenti, Luca, Vos, Miriam B., Wong, Vincent Wai-Sun, Xanthakos, Stavra, Yilmaz, Yusuf, Younossi, Zobair, Hobbs, Ansley, Villota-Rivas, Marcela, and Newsome, Philip N.
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- 2024
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45. Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study
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Abdelmalek, Manal F., Sanyal, Arun J., Nakajima, Atsushi, Neuschwander-Tetri, Brent A., Goodman, Zachary D., Lawitz, Eric J., Harrison, Stephen A., Jacobson, Ira M., Imajo, Kento, Gunn, Nadege, Halegoua-DeMarzio, Dina, Akahane, Takemi, Boone, Bradly, Yamaguchi, Masayuki, Chatterjee, Arkendu, Tirucherai, Giridhar S., Shevell, Diane E., Du, Shuyan, Charles, Edgar D., and Loomba, Rohit
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- 2024
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46. Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study
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Loomba, Rohit, Sanyal, Arun J., Nakajima, Atsushi, Neuschwander-Tetri, Brent A., Goodman, Zachary D., Harrison, Stephen A., Lawitz, Eric J., Gunn, Nadege, Imajo, Kento, Ravendhran, Natarajan, Akahane, Takemi, Boone, Bradly, Yamaguchi, Masayuki, Chatterjee, Arkendu, Tirucherai, Giridhar S., Shevell, Diane E., Du, Shuyan, Charles, Edgar D., and Abdelmalek, Manal F.
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- 2024
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47. Cenicriviroc Lacked Efficacy to Treat Liver Fibrosis in Nonalcoholic Steatohepatitis: AURORA Phase III Randomized Study
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Anstee, Quentin M., Neuschwander-Tetri, Brent A., Wai-Sun Wong, Vincent, Abdelmalek, Manal F., Rodriguez-Araujo, Gerardo, Landgren, Henrik, Park, Grace S., Bedossa, Pierre, Alkhouri, Naim, Tacke, Frank, and Sanyal, Arun J.
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- 2024
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48. Tropifexor for nonalcoholic steatohepatitis: an adaptive, randomized, placebo-controlled phase 2a/b trial
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Sanyal, Arun J., Lopez, Patricia, Lawitz, Eric J., Lucas, Kathryn J., Loeffler, Juergen, Kim, Won, Goh, George B. B., Huang, Jee-Fu, Serra, Carla, Andreone, Pietro, Chen, Yi-Cheng, Hsia, Stanley H., Ratziu, Vlad, Aizenberg, Diego, Tobita, Hiroshi, Sheikh, Aasim M., Vierling, John M., Kim, Yoon Jun, Hyogo, Hideyuki, Tai, Dean, Goodman, Zachary, Schaefer, Felicity, Carbarns, Ian R. I., Lamle, Sophie, Martic, Miljen, Naoumov, Nikolai V., and Brass, Clifford A.
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- 2023
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49. Patient Determinants for Histologic Diagnosis of NAFLD in the Real World: A TARGET‐NASH Study
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Barritt, A Sidney, Watkins, Stephanie, Gitlin, Norman, Klein, Samuel, Lok, Anna S, Loomba, Rohit, Schoen, Cheryl, Reddy, K Rajender, Trinh, Huy Ngoc, Mospan, Andrea R, Vos, Miriam B, Weiss, L Michael, Cusi, Kenneth, Neuschwander‐Tetri, Brent A, and Sanyal, Arun J
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Biomedical and Clinical Sciences ,Clinical Sciences ,Liver Disease ,Digestive Diseases ,Chronic Liver Disease and Cirrhosis ,Hepatitis ,Clinical Research ,Good Health and Well Being ,Clinical sciences - Abstract
Much of the current data on nonalcoholic fatty liver disease (NAFLD) are derived from biopsy-based studies that may introduce ascertainment and selection bias. Selection of patients for liver biopsy has implications for clinical practice and the reported epidemiology of NAFLD. The aim of this study was to determine patient factors predictive of histologic versus empiric clinical diagnosis of NAFLD in real-world practice. Adults from TARGET-NASH were included in this study. Descriptive statistics are provided for the cohort and compare the characteristics of histologic NAFLD versus patients with clinically diagnosed NAFLD, followed by logistic regression and machine-learning models to describe predictors of liver biopsy. The records of 3,474 subjects were analyzed; median age was 59 years, 59% were female, 75% were White, and median body mass index was 32 kg/m2. Using histologic and/or clinical criteria, a diagnosis of nonalcoholic steatohepatitis was made in 37%, and cirrhosis in 33%. Comorbid conditions included cardiovascular disease (19%), mental health diagnoses (49%), and osteoarthritis (10%). Predictors of a biopsy diagnosis included White race, female sex, diabetes, and elevated alanine aminotransferase (ALT). ALT increased the odds of liver biopsy by 14% per 10-point rise. Machine-learning analyses showed non-White patients with ALT
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- 2021
50. Nonalcoholic fatty liver disease as a metabolic disease in humans: A literature review
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Cariou, Bertrand, Byrne, Christopher D, Loomba, Rohit, and Sanyal, Arun J
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Obesity ,Chronic Liver Disease and Cirrhosis ,Diabetes ,Hepatitis ,Liver Disease ,Nutrition ,Digestive Diseases ,Clinical Research ,Prevention ,2.1 Biological and endogenous factors ,Aetiology ,Oral and gastrointestinal ,Metabolic and endocrine ,Good Health and Well Being ,Diabetes Mellitus ,Type 2 ,Humans ,Insulin Resistance ,Liver ,Non-alcoholic Fatty Liver Disease ,Sodium-Glucose Transporter 2 Inhibitors ,fatty liver disease ,GLP‐ ,1 ,insulin resistance ,pharmaco‐ ,epidemiology ,type 2 diabetes ,GLP-1 ,pharmaco-epidemiology ,Clinical Sciences ,Endocrinology & Metabolism - Abstract
AimsTo conduct a systematic literature review to identify recent epidemiological, biomarker, genetic and clinical evidence that expands our understanding of nonalcoholic fatty liver disease (NAFLD) as a metabolic disorder.Materials and methodsWe performed a literature search using PubMed to identify trials, observational studies and meta-analyses published in the past 5 years.ResultsA total of 95 publications met prespecified inclusion criteria and reported on the interplay between NAFLD/nonalcoholic steatohepatitis (NASH) and metabolic dysfunction, in terms of disease burden and/or epidemiology (n = 10), pathophysiology, risk factors and associated conditions (n = 29), diagnosis and biomarkers (n = 34), and treatment approaches (n = 22). There is a growing body of evidence on the links between NAFLD/NASH pathogenesis and mechanisms of metabolic dysfunction, through liver lipid accumulation, insulin resistance, inflammation, apoptosis, and fibrogenic remodelling within the liver. The frequent co-occurrence of NAFLD with obesity, metabolic syndrome and type 2 diabetes supports this premise. Therapeutic approaches originally envisaged for type 2 diabetes or obesity (such as glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter-2 inhibitors, insulin sensitizers and bariatric surgery) have shown promising signs of benefit for patients with NAFLD/NASH.ConclusionsGiven the complex interplay between NAFLD and metabolic dysfunction, there is an urgent need for multidisciplinary collaboration and established protocols for care of patients with NAFLD that are individualized and ideally support reduction of overall metabolic risk as well as treatment for NASH.
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- 2021
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