The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial
Open accessAbstract
Background The bile acid derivative 6-ethylchenodeoxycholic acid (obeticholic acid) is a potent activator of the farnesoid X nuclear receptor that reduces liver fat and fibrosis in animal models of fatty liver disease. We assessed the efficacy of obeticholic acid in adult patients with non-alcoholic steatohepatitis.Methods We did a multicentre, double-blind, placebo-controlled, parallel group, randomised clinical trial at medical centres in the USA in patients with non-cirrhotic, non-alcoholic steatohepatitis to assess treatment with obeticholic acid given orally (25 mg daily) or placebo for 72 weeks. Patients were randomly assigned 1:1 using a computer-generated, centrally administered procedure, stratified by clinical centre and diabetes status. The primary outcome measure was improvement in centrally scored liver histology defined as a decrease in non-alcoholic fatty liver disease activity score by at least 2 points without worsening of fibrosis from baseline to the end of treatment. A planned interim analysis of change in alanine aminotransferase at 24 weeks undertaken before end-of-treatment (72 weeks) biopsies supported the decision to continue the trial (relative change in alanine aminotransferase -24%, 95% CI -45 to -3). A planned interim analysis of the primary outcome showed improved efficacy of obeticholic acid (p=0·0024) and supported a decision not to do end-of-treatment biopsies and end treatment early in 64 patients, but to continue the trial to obtain the 24-week post-treatment measures. Analyses were done by intention-to-treat. This trial was registered with ClinicalTrials.gov, number NCT01265498.Findings Between March 16, 2011, and Dec 3, 2012, 141 patients were randomly assigned to receive obeticholic acid and 142 to placebo. 50 (45%) of 110 patients in the obeticholic acid group who were meant to have biopsies at baseline and 72 weeks had improved liver histology compared with 23 (21%) of 109 such patients in the placebo group (relative risk 1·9, 95% CI 1·3 to 2·8; p=0·0002). 33 (23%) of 141 patients in the obeticholic acid developed pruritus compared with nine (6%) of 142 in the placebo group.Interpretation Obeticholic acid improved the histological features of non-alcoholic steatohepatitis, but its long-term benefits and safety need further clarification.Funding National Institute of Diabetes and Digestive and Kidney Diseases, Intercept Pharmaceuticals.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source doesn’t support the claim as written.
In the citing paper
“In addition, FXR regulates other pathways with direct antiinflammatory and antifibrotic effects. 13-15”
From A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis (2016) · cites this paper as [14]
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Although OCA was generally well tolerated, concerns were raised by the occurrence of side effects such as pruritus, which developed in 23% of patients on OCA without leading to drug discontinuation, increased total serum cholesterol and low-density lipoprotein (LDL)-cholesterol levels and a modest, but significant, reduction in high-density lipoprotein (HDL)-cholesterol [83].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Pruritus was the main side effect of obeticholic acid (33% vs. 6% placebo) [46].”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [46]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Importantly however obeticholic acid improved fibrosis in 35% of patients versus only 19% in the placebo arm (p = 0.004) [46].”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [46]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Significantly more patients in the obeticholic acid arm (45%) versus placebo (21%) showed improved liver histology [46] (defined as decrease in NAS ≥2 points without worsening of fibrosis).”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [46]
The cited source says what the claim attributes to it.
In the citing paper
“Nevertheless, while the primary endpoint was reached, no statistically significant effect on the resolution of NASH was seen, which could limit direct clinical usefulness.”
From Current treatment of non‐alcoholic fatty liver disease (2022) · cites this paper as [46]
The cited source says what the claim attributes to it.
In the citing paper
“The drug is approved at a 5 or 10 mg daily dose for second-line therapy in primary biliary cholangitis 379 and was developed for MASH at a higher dose (25 mg daily), based on a phase II placebo-controlled trial showing improvement in fi brosis and liver enzymes after 18 months of treatment.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [380]
In the citing paper
“Although patients treated with OCA showed a significant improvement in the NAFLD activity score (i.e., the primary histological outcome) and a significant decrease in liver fibrosis, NASH resolution occurred in only 22% of patients treated with OCA (without a statically significant effect compared to placebo), and no effect was observed in patients with advanced fibrosis.”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“Although OCA was generally well tolerated, concerns were raised by the occurrence of side effects such as pruritus, which developed in 23% of patients on OCA without leading to drug discontinuation, increased total serum cholesterol and low-density lipoprotein (LDL)-cholesterol levels and a modest, but significant, reduction in high-density lipoprotein (HDL)-cholesterol [83].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“Although OCA was generally well tolerated, concerns were raised by the occurrence of side effects such as pruritus, which developed in 23% of patients on OCA without leading to drug discontinuation, increased total serum cholesterol and low-density lipoprotein (LDL)-cholesterol levels and a modest, but significant, reduction in high-density lipoprotein (HDL)-cholesterol [83].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“Although patients treated with OCA showed a significant improvement in the NAFLD activity score (i.e., the primary histological outcome) and a significant decrease in liver fibrosis, NASH resolution occurred in only 22% of patients treated with OCA (without a statically significant effect compared to placebo), and no effect was observed in patients with advanced fibrosis.”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“Although patients treated with OCA showed a significant improvement in the NAFLD activity score (i.e., the primary histological outcome) and a significant decrease in liver fibrosis, NASH resolution occurred in only 22% of patients treated with OCA (without a statically significant effect compared to placebo), and no effect was observed in patients with advanced fibrosis.”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“Although patients treated with OCA showed a significant improvement in the NAFLD activity score (i.e., the primary histological outcome) and a significant decrease in liver fibrosis, NASH resolution occurred in only 22% of patients treated with OCA (without a statically significant effect compared to placebo), and no effect was observed in patients with advanced fibrosis.”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“Although OCA was generally well tolerated, concerns were raised by the occurrence of side effects such as pruritus, which developed in 23% of patients on OCA without leading to drug discontinuation, increased total serum cholesterol and low-density lipoprotein (LDL)-cholesterol levels and a modest, but significant, reduction in high-density lipoprotein (HDL)-cholesterol [83].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [83]
In the citing paper
“OCA is a semisynthetic bile acid analogue that improved histological features of NASH and fibrosis in phase IIb clinical trials (35).”
From Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis (2016) · cites this paper as [35]
In the citing paper
“FLINT (phase 2b)77: 25 mg OCA for 18 months improved NAFLD activity score (predefined primary endpoint) and its individual components, but did not result in significantly higher NASH resolution (22 vs 13% compared with placebo); however, a higher proportion of patients (35 vs 19%) showed improved fibrosis (by at least one stage).”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [77]
In the citing paper
“Although OCA was validated in several clinical trials for its benefit in ameliorating NASH-induced liver fibrosis51,52, the response rate was 23%, far from satisfactory19,20.”
From SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis (2020) · cites this paper as [52]
In the citing paper
“OCA has a high safety profile in patients with NASH as demonstrated in the FLINT trial, with the major adverse effects being pruritus and alterations of serum lipid profiles144.”
From The gut microbiome and liver cancer: mechanisms and clinical translation (2017) · cites this paper as [144]
In the citing paper
“Given the potential for NF-kB to cause cardiac hypertrophy independent of processes such as hypertension, this presents indirect evidence for the potential of FXR-targeted therapies to improve heart failure144,145.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [144]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Design and validation of a histological scoring system for nonalcoholic fatty liver disease†
Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., Ferrell, L. D., Liu, Y., Torbenson, M. S., Unalp‐Arida, A., et al. (2005) · Hepatology · doi:10.1002/hep.20701 · Cited by 10,791
Self-citationChalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Hepatology · doi:10.1002/hep.25762 · Cited by 3,859
Self-citationPioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis
Sanyal, A. J., Chalasani, N., Kowdley, K. V., McCullough, A., Diehl, A. M., Bass, N. M., Neuschwander-Tetri, B. A., Lavine, J. E., Tonascia, J., Unalp, A., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa0907929 · Cited by 3,327
Self-citationBrunt, E. M., Kleiner, D. E., Wilson, L. A., Belt, P., & Neuschwander-Tetri, B. A. (2011) · Hepatology · doi:10.1002/hep.24127 · Cited by 1,251
Self-citationPleiotropic Roles of Bile Acids in Metabolism
de Aguiar Vallim, T. Q., Tarling, E. J., & Edwards, P. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.013 · Cited by 1,209
Cusi, K. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.02.003 · Cited by 940
Mudaliar, S., Henry, R. R., Sanyal, A. J., Morrow, L., Marschall, H., Kipnes, M., Adorini, L., Sciacca, C. I., Clopton, P., Castelloe, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.042 · Cited by 931
Self-citationTranscriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR
Calkin, A. C., & Tontonoz, P. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3312 · Cited by 779
Ursodeoxycholic acid for treatment of nonalcoholic steatohepatitis: results of a randomized trial
Lindor, K. D., Kowdley, K. V., Heathcote, J. E., Harrison, E. M., Jorgensen, R., Angulo, P., Lymp, J. F., Burgart, L., & Colin, P. (2004) · Hepatology · doi:10.1002/hep.20092 · Cited by 727
Self-citationMarrero, J., Fontana, R. J., Su, G. L., Conjeevaram, H. S., Emick, D. M., & Lok, A. S.-F. (2002) · Hepatology · doi:10.1053/jhep.2002.36939 · Cited by 659
Cited by
Sorted by citations
Chalasani, N., Younossi, Z., Lavine, J. E., Charlton, M., Cusi, K., Rinella, M., Harrison, S. A., Brunt, E. M., & Sanyal, A. J. (2018) · Hepatology · doi:10.1002/hep.29367 · Cited by 7,239
Self-citationEASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
(2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.11.004 · Cited by 4,836
Mechanisms of NAFLD development and therapeutic strategies
Friedman, S. L., Neuschwander-Tetri, B. A., Rinella, M., & Sanyal, A. J. (2018) · Nature Medicine · doi:10.1038/s41591-018-0104-9 · Cited by 4,354
Self-citationNon-alcoholic fatty liver disease
Powell, E. E., Wong, V. W.-S., & Rinella, M. (2021) · The Lancet · doi:10.1016/s0140-6736(20)32511-3 · Cited by 2,789
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611
Tacke, F., Horn, P., Wai-Sun Wong, V., Ratziu, V., Bugianesi, E., Francque, S., Zelber-Sagi, S., Valenti, L., Roden, M., Schick, F., et al. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.031 · Cited by 2,210
The gut-liver axis in liver disease: Pathophysiological basis for therapy
Albillos, A., de Gottardi, A., & Rescigno, M. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2019.10.003 · Cited by 2,166
Armstrong, M. J., Gaunt, P., Aithal, G. P., Barton, D., Hull, D., Parker, R., Hazlehurst, J. M., Guo, K., Abouda, G., Aldersley, M. A., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00803-x · Cited by 2,203
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002
Self-citationA Placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis
Newsome, P. N., Buchholtz, K., Cusi, K., Linder, M., Okanoue, T., Ratziu, V., Sanyal, A. J., Sejling, A.-S., & Harrison, S. A. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2028395 · Cited by 2,039
Self-citationMolecular mechanisms of hepatic lipid accumulation in non-alcoholic fatty liver disease
Ipsen, D. H., Lykkesfeldt, J., & Tveden-Nyborg, P. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2860-6 · Cited by 1,471
The gut-liver axis and the intersection with the microbiome
Tripathi, A., Debelius, J., Brenner, D. A., Karin, M., Loomba, R., Schnabl, B., & Knight, R. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0011-z · Cited by 1,480
Self-citationLiver inflammation and fibrosis
Koyama, Y., & Brenner, D. A. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88881 · Cited by 1,295
Younossi, Z. M., Ratziu, V., Loomba, R., Rinella, M., Anstee, Q. M., Goodman, Z., Bedossa, P., Geier, A., Beckebaum, S., Newsome, P. N., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)33041-7 · Cited by 1,277
Self-citationLiver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives
Roehlen, N., Crouchet, E., & Baumert, T. F. (2020) · Cells · doi:10.3390/cells9040875 · Cited by 1,237
Bile acids and the gut microbiota: metabolic interactions and impacts on disease
Collins, S. L., Stine, J. G., Bisanz, J. E., Okafor, C. D., & Patterson, A. D. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00805-x · Cited by 1,214
Dietary lipids, gut microbiota and lipid metabolism
Schoeler, M., & Caesar, R. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09512-0 · Cited by 1,163
Prospective Study of Outcomes in Adults with Nonalcoholic Fatty Liver Disease
Sanyal, A. J., Van Natta, M. L., Clark, J., Neuschwander-Tetri, B. A., Diehl, A., Dasarathy, S., Loomba, R., Chalasani, N., Kowdley, K., Hameed, B., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2029349 · Cited by 1,146
Self-citationA Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis
Nevens, F., Andreone, P., Mazzella, G., Strasser, S. I., Bowlus, C., Invernizzi, P., Drenth, J. P. H., Pockros, P. J., Regula, J., Beuers, U., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1509840 · Cited by 1,131
Self-citationTaylor, R. S., Taylor, R. J., Bayliss, S., Hagström, H., Nasr, P., Schattenberg, J. M., Ishigami, M., Toyoda, H., Wai-Sun Wong, V., Peleg, N., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.01.043 · Cited by 1,069
Ratziu, V., Harrison, S. A., Francque, S., Bedossa, P., Lehert, P., Serfaty, L., Romero-Gomez, M., Boursier, J., Abdelmalek, M., Caldwell, S., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.038 · Cited by 1,035
Self-citationThe role of the gut microbiota in NAFLD
Leung, C., Rivera, L., Furness, J. B., & Angus, P. W. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.85 · Cited by 1,020
Cusi, K., Orsak, B., Bril, F., Lomonaco, R., Hecht, J., Ortiz-Lopez, C., Tio, F., Hardies, J., Darland, C., Musi, N., et al. (2016) · Annals of Internal Medicine · doi:10.7326/m15-1774 · Cited by 1,024
The role of macrophages in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Kazankov, K., Jørgensen, S. M. D., Thomsen, K. L., Møller, H. J., Vilstrup, H., George, J., Schuppan, D., & Grønbæk, H. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0082-x · Cited by 941
Chávez-Talavera, O., Tailleux, A., Lefebvre, P., & Staels, B. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.055 · Cited by 970
Lipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847
The complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments
Targher, G., Corey, K. E., Byrne, C. D., & Roden, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00448-y · Cited by 850
Harrison, S. A., Bashir, M. R., Guy, C. D., Zhou, R., Moylan, C. A., Frias, J. P., Alkhouri, N., Bansal, M. B., Baum, S., Neuschwander-Tetri, B. A., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32517-6 · Cited by 802
Self-citationDietary metabolism, the gut microbiome, and heart failure
Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789
Nonalcoholic fatty liver disease as a nexus of metabolic and hepatic diseases
Samuel, V. T., & Shulman, G. I. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.002 · Cited by 745
“Despite the improvement in hepatic steatosis, there was an increase in fasting serum insulin concentrations, raising the possibility of worsening insulin resistance (Neuschwander-Tetri et al., 2015).”
Duell, P. B., Welty, F. K., Miller, M., Chait, A., Hammond, G., Ahmad, Z., Cohen, D. E., Horton, J. D., Pressman, G. S., Toth, P. P., et al. (2022) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atv.0000000000000153 · Cited by 727
Hepatic fibrosis: concept to treatment
Trautwein, C., Friedman, S. L., Schuppan, D., & Pinzani, M. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.02.039 · Cited by 677
Mouries, J., Brescia, P., Silvestri, A., Spadoni, I., Sorribas, M., Wiest, R., Mileti, E., Galbiati, M., Invernizzi, P., Adorini, L., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.08.005 · Cited by 688
Friedman, S. L., Ratziu, V., Harrison, S. A., Abdelmalek, M. F., Aithal, G. P., Caballeria, J., Francque, S., Farrell, G., Kowdley, K. V., Craxi, A., et al. (2018) · Hepatology · doi:10.1002/hep.29477 · Cited by 671
Self-citationBile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives
Arab, J. P., Karpen, S. J., Dawson, P. A., Arrese, M., & Trauner, M. (2017) · Hepatology · doi:10.1002/hep.28709 · Cited by 634
The gut microbiome and liver cancer: mechanisms and clinical translation
Yu, L.-X., & Schwabe, R. F. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.72 · Cited by 634
Apoptosis and necroptosis in the liver: a matter of life and death
Schwabe, R. F., & Luedde, T. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0065-y · Cited by 582
Recent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573
Modeling Steatohepatitis in Humans with Pluripotent Stem Cell-Derived Organoids
Ouchi, R., Togo, S., Kimura, M., Shinozawa, T., Koido, M., Koike, H., Thompson, W., Karns, R. A., Mayhew, C. N., McGrath, P. S., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.05.007 · Cited by 537
Past, present and future perspectives in nonalcoholic fatty liver disease
Sanyal, A. J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0144-8 · Cited by 522
Self-citationBile Acid-Activated Receptors, Intestinal Microbiota, and the Treatment of Metabolic Disorders
Fiorucci, S., & Distrutti, E. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2015.09.001 · Cited by 539
Randomized, Controlled Trial of the FGF21 Analogue Pegozafermin in NASH
Loomba, R., Sanyal, A. J., Kowdley, K. V., Bhatt, D. L., Alkhouri, N., Frias, J. P., Bedossa, P., Harrison, S. A., Lazas, D., Barish, R., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2304286 · Cited by 522
Self-citationMolecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481
Role of bile acids in metabolic control
Molinaro, A., Wahlström, A., & Marschall, H.-U. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.11.002 · Cited by 447
Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., et al. (2018) · Hepatology · doi:10.1002/hep.29359 · Cited by 426
Self-citationHarrison, S. A., Rinella, M. E., Abdelmalek, M. F., Trotter, J. F., Paredes, A. H., Arnold, H. L., Kugelmas, M., Bashir, M. R., Jaros, M. J., Ling, L., et al. (2018) · The Lancet · doi:10.1016/s0140-6736(18)30474-4 · Cited by 425
Self-citationNonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus
Targher, G., Lonardo, A., & Byrne, C. D. (2018) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.173 · Cited by 397
Malehmir, M., Pfister, D., Gallage, S., Szydlowska, M., Inverso, D., Kotsiliti, E., Leone, V., Peiseler, M., Surewaard, B. G. J., Rath, D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0379-5 · Cited by 398
Eriksson, J. W., Lundkvist, P., Jansson, P.-A., Johansson, L., Kvarnström, M., Moris, L., Miliotis, T., Forsberg, G.-B., Risérus, U., Lind, L., et al. (2018) · Diabetologia · doi:10.1007/s00125-018-4675-2 · Cited by 396
Harrison, S. A., Abdelmalek, M. F., Caldwell, S., Shiffman, M. L., Diehl, A. M., Ghalib, R., Lawitz, E. J., Rockey, D. C., Schall, R. A., Jia, C., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.07.006 · Cited by 384
Self-citationAminian, A., Al-Kurd, A., Wilson, R., Bena, J., Fayazzadeh, H., Singh, T., Albaugh, V. L., Shariff, F. U., Rodriguez, N. A., Jin, J., et al. (2021) · JAMA · doi:10.1001/jama.2021.19569 · Cited by 375
Self-citationChu, H., Duan, Y., Yang, L., & Schnabl, B. (2019) · Gut · doi:10.1136/gutjnl-2018-316307 · Cited by 354
Chalasani, N., Abdelmalek, M. F., Garcia-Tsao, G., Vuppalanchi, R., Alkhouri, N., Rinella, M., Noureddin, M., Pyko, M., Shiffman, M., Sanyal, A., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.11.296 · Cited by 358
Self-citationManagement of nonalcoholic fatty liver disease in patients with type 2 diabetes: a call to action
Bril, F., & Cusi, K. (2017) · Diabetes Care · doi:10.2337/dc16-1787 · Cited by 341
Musso, G., Cassader, M., Paschetta, E., & Gambino, R. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.06.031 · Cited by 332
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Pafili, K., & Roden, M. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101122 · Cited by 330
Lefebvre, E., Moyle, G., Reshef, R., Richman, L. P., Thompson, M., Hong, F., Chou, H.-L., Hashiguchi, T., Plato, C., Poulin, D., et al. (2016) · PLOS ONE · doi:10.1371/journal.pone.0158156 · Cited by 323
Nahra, R., Wang, T., Gadde, K. M., Oscarsson, J., Stumvoll, M., Jermutus, L., Hirshberg, B., & Ambery, P. (2021) · Diabetes Care · doi:10.2337/dc20-2151 · Cited by 323
Current treatment of non‐alcoholic fatty liver disease
Paternostro, R., & Trauner, M. (2022) · Journal of Internal Medicine · doi:10.1111/joim.13531 · Cited by 305
Risk of cardiomyopathy and cardiac arrhythmias in patients with nonalcoholic fatty liver disease
Anstee, Q. M., Mantovani, A., Tilg, H., & Targher, G. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0010-0 · Cited by 310
Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis
Kowdley, K. V., Bowlus, C. L., Levy, C., Akarca, U. S., Alvares-da-Silva, M. R., Andreone, P., Arrese, M., Corpechot, C., Francque, S. M., Heneghan, M. A., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2306185 · Cited by 314
Self-citationMutations in the nuclear bile acid receptor FXR cause progressive familial intrahepatic cholestasis
Gomez-Ospina, N., Potter, C. J., Xiao, R., Manickam, K., Kim, M.-S., Kim, K. H., Shneider, B. L., Picarsic, J. L., Jacobson, T. A., Zhang, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms10713 · Cited by 300
The effects of physical exercise on fatty liver disease.
van der Windt, D. J., Sud, V., Zhang, H., Tsung, A., & Huang, H. (2018) · Gene Expression · doi:10.3727/105221617x15124844266408 · Cited by 294
Loomba, R., Noureddin, M., Kowdley, K. V., Kohli, A., Sheikh, A., Neff, G., Bhandari, B. R., Gunn, N., Caldwell, S. H., Goodman, Z., et al. (2021) · Hepatology · doi:10.1002/hep.31622 · Cited by 296
Self-citationHartmann, P., Hochrath, K., Horvath, A., Chen, P., Seebauer, C. T., Llorente, C., Wang, L., Alnouti, Y., Fouts, D. E., Stärkel, P., et al. (2018) · Hepatology · doi:10.1002/hep.29676 · Cited by 290
Nevola, R., Epifani, R., Imbriani, S., Tortorella, G., Aprea, C., Galiero, R., Rinaldi, L., Marfella, R., & Sasso, F. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021703 · Cited by 286
Gastrointestinal Complications of Obesity
Camilleri, M., Malhi, H., & Acosta, A. (2017) · Gastroenterology · doi:10.1053/j.gastro.2016.12.052 · Cited by 269
Ibrahim, S. H., Hirsova, P., & Gores, G. J. (2018) · Gut · doi:10.1136/gutjnl-2017-315691 · Cited by 278
Diagnostic accuracy of noninvasive fibrosis models to detect change in fibrosis stage
Siddiqui, M. S., Yamada, G., Vuppalanchi, R., Van Natta, M., Loomba, R., Guy, C., Brandman, D., Tonascia, J., Chalasani, N., Neuschwander-Tetri, B., et al. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.12.031 · Cited by 272
Self-citationBoland, M. L., Laker, R. C., Mather, K., Nawrocki, A., Oldham, S., Boland, B. B., Lewis, H., Conway, J., Naylor, J., Guionaud, S., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0209-6 · Cited by 270
Lipotoxic lethal and sublethal stress signaling in hepatocytes: relevance to NASH pathogenesis
Hirsova, P., Ibrabim, S. H., Gores, G. J., & Malhi, H. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r066357 · Cited by 270
The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism
Just, S., Mondot, S., Ecker, J., Wegner, K., Rath, E., Gau, L., Streidl, T., Hery-Arnaud, G., Schmidt, S., Lesker, T. R., et al. (2018) · Microbiome · doi:10.1186/s40168-018-0510-8 · Cited by 269
A randomized trial of silymarin for the treatment of nonalcoholic steatohepatitis
Wah Kheong, C., Nik Mustapha, N. R., & Mahadeva, S. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.04.016 · Cited by 264
Harrison, S. A., Rossi, S. J., Paredes, A. H., Trotter, J. F., Bashir, M. R., Guy, C. D., Banerjee, R., Jaros, M. J., Owers, S., Baxter, B. A., et al. (2020) · Hepatology · doi:10.1002/hep.30590 · Cited by 262
Nonalcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus
Dharmalingam, M., & Yamasandhi, P. (2018) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_585_17 · Cited by 239
Non-alcoholic fatty liver and the gut microbiota
Bashiardes, S., Shapiro, H., Rozin, S., Shibolet, O., & Elinav, E. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.003 · Cited by 241
Verbeke, L., Mannaerts, I., Schierwagen, R., Govaere, O., Klein, S., Vander Elst, I., Windmolders, P., Farre, R., Wenes, M., Mazzone, M., et al. (2016) · Scientific Reports · doi:10.1038/srep33453 · Cited by 236
New therapeutic concepts in bile acid transport and signaling for management of cholestasis
Trauner, M., Fuchs, C. D., Halilbasic, E., & Paumgartner, G. (2017) · Hepatology · doi:10.1002/hep.28991 · Cited by 227
Nonalcoholic fatty liver disease in adults: current concepts in etiology, outcomes, and management
Marjot, T., Moolla, A., Cobbold, J. F., Hodson, L., & Tomlinson, J. W. (2020) · Endocrine Reviews · doi:10.1210/endrev/bnz009 · Cited by 228
Ratziu, V., de Guevara, L., Safadi, R., Poordad, F., Fuster, F., Flores-Figueroa, J., Arrese, M., Fracanzani, A. L., Ben Bashat, D., Lackner, K., et al. (2021) · Nature Medicine · doi:10.1038/s41591-021-01495-3 · Cited by 222
Self-citationRao, A., Kosters, A., Mells, J. E., Zhang, W., Setchell, K. D. R., Amanso, A. M., Wynn, G. M., Xu, T., Keller, B. T., Yin, H., et al. (2016) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf4823 · Cited by 211
Novel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204
Combination therapy for non-alcoholic steatohepatitis: rationale, opportunities and challenges
Dufour, J.-F., Caussy, C., & Loomba, R. (2020) · Gut · doi:10.1136/gutjnl-2019-319104 · Cited by 193
Self-citationVilar‐Gomez, E., Vuppalanchi, R., Gawrieh, S., Ghabril, M., Saxena, R., Cummings, O. W., & Chalasani, N. (2020) · Hepatology · doi:10.1002/hep.30368 · Cited by 193
Self-citationHirschfield, G. M., Chazouillères, O., Drenth, J. P., Thorburn, D., Harrison, S. A., Landis, C. S., Mayo, M. J., Muir, A. J., Trotter, J. F., Leeming, D. J., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2018.10.035 · Cited by 187
Newsome, P., Francque, S., Harrison, S., Ratziu, V., Van Gaal, L., Calanna, S., Hansen, M., Linder, M., & Sanyal, A. (2019) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15316 · Cited by 186
Self-citationHuang, D. Q., Wilson, L. A., Behling, C., Kleiner, D. E., Kowdley, K. V., Dasarathy, S., Amangurbanova, M., Terrault, N. A., Diehl, A. M., Chalasani, N., et al. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.04.025 · Cited by 190
Self-citationTrauner, M., Nevens, F., Shiffman, M. L., Drenth, J. P. H., Bowlus, C. L., Vargas, V., Andreone, P., Hirschfield, G. M., Pencek, R., Malecha, E. S., et al. (2019) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30094-9 · Cited by 180
Intestinal Microbiota and Nonalcoholic Steatohepatitis
Brandl, K., & Schnabl, B. (2017) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000349 · Cited by 169
Schwabl, P., Hambruch, E., Seeland, B. A., Hayden, H., Wagner, M., Garnys, L., Strobel, B., Schubert, T.-L., Riedl, F., Mitteregger, D., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2016.12.005 · Cited by 178
Nonalcoholic fatty liver disease: cause or consequence of type 2 diabetes?
Valenti, L., Bugianesi, E., Pajvani, U., & Targher, G. (2016) · Liver International · doi:10.1111/liv.13185 · Cited by 171
Alkhouri, N., Lawitz, E., Noureddin, M., DeFronzo, R., & Shulman, G. I. (2020) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2020.1668374 · Cited by 162
Rinella, M. E., Dufour, J.-F., Anstee, Q. M., Goodman, Z., Younossi, Z., Harrison, S. A., Loomba, R., Sanyal, A. J., Bonacci, M., Trylesinski, A., et al. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2021.10.029 · Cited by 164
Han, Y.-H., Shin, K.-O., Kim, J.-Y., Khadka, D. B., Kim, H.-J., Lee, Y.-M., Cho, W.-J., Cha, J.-Y., Lee, B.-J., & Lee, M.-O. (2019) · Journal of Clinical Investigation · doi:10.1172/jci124219 · Cited by 154
Brunt, E. M., Kleiner, D. E., Wilson, L. A., Sanyal, A. J., Neuschwander‐Tetri, B. A., & for the Nonalcoholic Steatohepatitis Clinical Research Network (2019) · Hepatology · doi:10.1002/hep.30418 · Cited by 154
Development of an in vitro human liver system for interrogating nonalcoholic steatohepatitis
Feaver, R. E., Cole, B. K., Lawson, M. J., Hoang, S. A., Marukian, S., Blackman, B. R., Figler, R. A., Sanyal, A. J., Wamhoff, B. R., & Dash, A. (2016) · JCI Insight · doi:10.1172/jci.insight.90954 · Cited by 153
Self-citationZhou, M., Learned, R. M., Rossi, S. J., DePaoli, A. M., Tian, H., & Ling, L. (2017) · Hepatology Communications · doi:10.1002/hep4.1108 · Cited by 152
Human Multilineage 3D Spheroids as a Model of Liver Steatosis and Fibrosis
Pingitore, P., Sasidharan, K., Ekstrand, M., Prill, S., Lindén, D., & Romeo, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20071629 · Cited by 152
SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis
Zhou, J., Cui, S., He, Q., Guo, Y., Pan, X., Zhang, P., Huang, N., Ge, C., Wang, G., Gonzalez, F. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14138-6 · Cited by 154
Breakthroughs in therapies for NASH and remaining challenges
Ratziu, V., Francque, S., & Sanyal, A. (2022) · Journal of Hepatology · doi:10.1016/j.jhep.2022.04.002 · Cited by 132
Self-citation
Metadata
- Authors
- Neuschwander-Tetri, B. A., Loomba, R., Sanyal, A. J., Lavine, J. E., Van Natta, M. L., Abdelmalek, M. F., Chalasani, N., Dasarathy, S., Diehl, A. M., Hameed, B., Kowdley, K. V., McCullough, A., Terrault, N., Clark, J. M., Tonascia, J., Brunt, E. M., Kleiner, D. E., & Doo, E.
- Affiliations
- University of California San Diego (US)
- Virginia Commonwealth University (US)
- Columbia University (US)
- Duke University (US)
- Indiana University Indianapolis (US)
- Case Western Reserve University (US)
- University of California, San Francisco (US)
- Virginia Mason Medical Center (US)
- Cleveland Clinic (US)
- Johns Hopkins University (US)
- Washington University in St. Louis (US)
- National Cancer Institute (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- ORCID
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2015-03
- Volume
- 385
- Issue
- 9972
- Pages
- 956-965
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- PMC
- PMC4447192
- OpenAlex
- W2106768039
- Cited by
- 2,237
- References
- 30
- Citations by year
- 2026: 89 · 2025: 111 · 2024: 145 · 2023: 159 · 2022: 192 · 2021: 236 · 2020: 264 · 2019: 245 · 2018: 234 · 2017: 229 · 2016: 190 · 2015: 130
- FWCI
- 139.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (grants U01DK061718, U01DK061728, U01DK061731, U01DK061732, U01DK061734, U01DK061737, U01DK061738, U01DK061730, U01DK061713)
- National Center for Advancing Translational Sciences (NCATS) for NASH CRN Studies (grants UL1TR000439, UL1TR000436, UL1TR000006, UL1TR000448, UL1TR000100, UL1TR000004, UL1TR000423, and UL1TR000058)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- obeticholic acid, nonalcoholic steatohepatitis, non-cirrhotic liver disease, bile acid derivatives, liver histopathology, liver fibrosis, alanine aminotransferase, treatment discontinuation
- MeSH terms
- Receptor, Farnesoid X-Activated, Administration, Oral, Chenodeoxycholic Acid, Double-Blind Method, Female, Humans, Cholesterol, HDL, Cholesterol, LDL, Liver, Liver Cirrhosis, Male, Middle Aged, Weight Loss, Treatment Outcome, Receptors, Cytoplasmic and Nuclear, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
