A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis
Abstract
Background & aims Nonalcoholic steatohepatitis (NASH) is a prevalent liver disease associated with increased morbidity and mortality. Ursodeoxycholic acid (UDCA) may have antioxidant, anti-inflammatory, and antifibrotic properties and may reduce liver injury in NASH. To date, no studies have assessed the efficacy and safety of high-dose UDCA (HD-UDCA) in patients with NASH.Methods We conducted a 12-month, randomized, double-blind, placebo-controlled multicenter trial to evaluate the efficacy and safety of HD-UDCA (28-35 mg/kg per day) in 126 patients with biopsy-proven NASH and elevated alanine aminotransferase (ALT) levels. The primary study end point was reduction in ALT levels from baseline in patients treated with HD-UDCA compared with placebo. Secondary study end points were the proportion of patients with ALT normalization, relative reduction in the scores of serum markers of fibrosis and hepatic inflammation, and safety and tolerability.Results HD-UDCA significantly reduced mean ALT levels -28.3% from baseline after 12 months compared with -1.6% with placebo (p<0.001). At the end of the trial, ALT levels normalized (≤35 IU/L) in 24.5% of patients treated with HD-UDCA and in 4.8% of patients who received placebo (p=0.003). Both results were not accounted for by changes in weight during the trial. HD-UDCA significantly reduced the FibroTest® serum fibrosis marker (p<0.001) compared with placebo. HD-UDCA also significantly improved markers of glycemic control and insulin resistance. There were no safety issues in this population.Conclusions Treatment with HD-UDCA was safe, improved aminotransferase levels, serum fibrosis markers, and selected metabolic parameters. Studies with histologic end points are warranted.
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There are three larger, placebo-controlled trials of UDCA in MASH differing in dose, and only two report histological endpoints.
“There are three larger, placebo-controlled trials of UDCA in MASH differing in the dose of UDCA used 373 -375 and only two of them report histological endpoints.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [375]
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 · see citing works
Angulo, P., Hui, J. M., Marchesini, G., Bugianesi, E., George, J., Farrell, G. C., Enders, F., Saksena, S., Burt, A. D., Bida, J. P., et al. (2007) · Hepatology · doi:10.1002/hep.21496 · Cited by 3,198 · see citing works
The Natural History of Nonalcoholic Fatty Liver Disease: A Population-Based Cohort Study
Adams, L. A., Lymp, J. F., St. Sauver, J., Sanderson, S. O., Lindor, K. D., Feldstein, A., & Angulo, P. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.04.014 · Cited by 2,890 · see citing works
Identification of a nuclear receptor for bile acids
Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J., & Shan, B. (1999) · Science · doi:10.1126/science.284.5418.1362 · Cited by 2,714 · see citing works
Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis
Farrell, G. C., & Larter, C. Z. (2006) · Hepatology · doi:10.1002/hep.20973 · Cited by 2,413 · see citing works
Özcan, U., Yilmaz, E., Özcan, L., Furuhashi, M., Vaillancourt, E., Smith, R. O., Görgün, C. Z., & Hotamisligil, G. S. (2006) · Science · doi:10.1126/science.1128294 · Cited by 2,413 · see citing works
Long-term follow-up of patients with NAFLD and elevated liver enzymes
Ekstedt, M., Franzén, L. E., Mathiesen, U. L., Thorelius, L., Holmqvist, M., Bodemar, G., & Kechagias, S. (2006) · Hepatology · doi:10.1002/hep.21327 · Cited by 2,302 · see citing works
Bile Acids: Natural Ligands for an Orphan Nuclear Receptor
Parks, D. J., Blanchard, S. G., Bledsoe, R. K., Chandra, G., Consler, T. G., Kliewer, S. A., Stimmel, J. B., Willson, T. M., Zavacki, A. M., Moore, D. D., et al. (1999) · Science · doi:10.1126/science.284.5418.1365 · Cited by 2,274 · see citing works
Protection from obesity-induced insulin resistance in mice lacking TNF-α function
Uysal, K. T., Wiesbrock, S. M., Marino, M. W., & Hotamisligil, G. S. (1997) · Nature · doi:10.1038/39335 · Cited by 2,234 · see citing works
A G Protein-coupled Receptor Responsive to Bile Acids
Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209706200 · Cited by 1,628 · see citing works
Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
渡辺, 光., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D., & Auwerx, J. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21025 · Cited by 1,398 · see citing works
Tumor necrosis factor alpha inhibits signaling from the insulin receptor.
Hotamışlıgil, G. S., Murray, D. L., Choy, L., & Spiegelman, B. M. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.11.4854 · Cited by 1,206 · see citing works
Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis
Feldstein, A. E., Canbay, A., Angulo, P., Taniai, M., Burgart, L. J., Lindor, K. D., & Gores, G. J. (2003) · Gastroenterology · doi:10.1016/s0016-5085(03)00907-7 · Cited by 1,085 · see citing works
Decreased Survival of Subjects With Elevated Liver Function Tests During A 28-Year Follow-Up
Söderberg, C., Stal, P. I., Askling, J., Glaumann, H., Lindberg, G., Marmur, J., & Hultcrantz, R. W. (2009) · Hepatology · doi:10.1002/hep.23314 · Cited by 748 · see citing works
Guha, I. N., Parkes, J., Roderick, P. J., Chattopadhyay, D., Cross, R., Harris, S., Kaye, P., Burt, A. D., Ryder, S. D., Aithal, G. P., et al. (2007) · Hepatology · doi:10.1002/hep.21984 · Cited by 744 · see citing works
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 · see citing works
High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis
Lindor, K. D., Kowdley, K. V., Luketic, V. A. C., Harrison, E. M., McCashland, T., Befeler, A. S., Harnois, D., Jorgensen, R., Petz, J., Keach, J., et al. (2009) · Hepatology · doi:10.1002/hep.23082 · Cited by 720 · see citing works
Bile-acid-induced cell injury and protection
Perez, M. J., & Briz, O. (2009) · World Journal of Gastroenterology · doi:10.3748/wjg.15.1677 · Cited by 717 · see citing works
Ratziu, V., Giral, P., Jacqueminet, S., Charlotte, F., Hartemann–Heurtier, A., Serfaty, L., Podevin, P., Lacorte, J., Bernhardt, C., Bruckert, E., et al. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.078 · Cited by 625 · see citing works
Laurin, J. M., Lindor, K., Crippin, J. S., Gossard, A. A., Gores, G. J., Ludwig, J., Rakela, J. L., & McGill, D. B. (1996) · Hepatology · doi:10.1002/hep.510230624 · Cited by 565 · see citing works
Rodrigues, C. M. P., Fan, G., Ma, X., Kren, B. T., & Steer, C. J. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1325 · Cited by 515 · see citing works
Caldwell, S. H., & Crespo, D. M. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.02.013 · Cited by 499 · see citing works
Ratziu, V., Massard, J., Charlotte, F., Messous, D., Imbert‐Bismut, F., Bonyhay, L., Tahiri, M., Munteanu, M., Thabut, D., Cadranel, J. F. D., et al. (2006) · BMC Gastroenterology · doi:10.1186/1471-230x-6-6 · Cited by 491 · see citing works
Weston, S. R., Leyden, W. A., Murphy, R., Bass, N. M., Bell, B. P., Manos, M. M., & Terrault, N. A. (2005) · Hepatology · doi:10.1002/hep.20554 · Cited by 361 · see citing works
Dufour, J., Oneta, C. M., Gonvers, J., Bihl, F. K., Cerny, A., Cereda, J., Zala, J., Helbling, B., Steuerwald, M., & Zimmermann, A. (2006) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2006.09.025 · Cited by 355 · see citing works
A preliminary trial of high-dose ursodeoxycholic acid in primary sclerosing cholangitis
Mitchell, S. A., Bansi, D. S., Hunt, N., Bergmann, K. V., Fleming, K. A., & Chapman, R. W. (2001) · Gastroenterology · doi:10.1053/gast.2001.27965 · Cited by 351 · see citing works
Effect of tauroursodeoxycholic acid on endoplasmic reticulum stress-induced caspase-12 activation
Xie, Q., Khaoustov, V. I., Chung, C. C., Sohn, J., Krishnan, B., Lewis, D. E., & Yoffe, B. (2002) · Hepatology · doi:10.1053/jhep.2002.35441 · Cited by 339 · see citing works
Rodrigues, C. M. P., Fan, G., Wong, P. Y., Kren, B. T., & Steer, C. J. (1998) · Molecular Medicine · doi:10.1007/bf03401914 · Cited by 335 · see citing works
Leuschner, U. F. H., Lindenthal, B., Herrmann, G., Arnold, J. C., Rössle, M., Cordes, H., Zeuzem, S., Hein, J., & Berg, T. (2010) · Hepatology · doi:10.1002/hep.23727 · Cited by 317 · see citing works
Sato, H., Macchiarulo, A., Thomas, C., Gioiello, A., Une, M., Hofmann, A. F., Saladin, R., Schoonjans, K., Pellicciari, R., & Auwerx, J. H. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7015864 · Cited by 302 · see citing works
Poynard, T., McHutchison, J. G., Manns, M. P., Myers, R., & Albrecht, J. K. (2003) · Hepatology · doi:10.1053/jhep.2003.50319 · Cited by 252 · see citing works
Comparison of blood tests for liver fibrosis specific or not to NAFLD
Calès, P., Lainé, F., Boursier, J., Deugnier, Y., Moal, V., Oberti, F., Hunault, G., Rousselet, M. C., Hubert, I., Laafi, J., et al. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.07.035 · Cited by 252 · see citing works
High-dose ursodeoxycholic acid as a therapy for patients with primary sclerosing cholangitis
Harnois, D. M., Angulo, P., Jorgensen, R. A., LaRusso, N. F., & Lindor, K. D. (2001) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2001.03777.x · Cited by 242 · see citing works
Poynard, T., Imbert‐Bismut, F., Ratziu, V., Chevret, S., Jardel, C., Moussalli, J., Messous, D., Degos, F., & for the GERMED cyt04 group (2002) · Journal of Viral Hepatitis · doi:10.1046/j.1365-2893.2002.00341.x · Cited by 219 · see citing works
Schreuder, T. C. M. A., Verwer, B. J., van Nieuwkerk, C. M., & Mulder, C. J. J. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.2474 · Cited by 189 · see citing works
Weight-Loss Diets for the Prevention and Treatment of Obesity
Katan, M. (2009) · New England Journal of Medicine · doi:10.1056/nejme0810291 · Cited by 166 · see citing works
Prognosis of patients with a diagnosis of fatty liver--a registry-based cohort study.
Jepsen, P., Vilstrup, H., Mellemkjær, L., Thulstrup, A. M., Olsen, J. H., Baron, J. A., & Sørensen, H. T. (2003) · PubMed · Cited by 152 · see citing works
Qiao, L., Yacoub, A., Studer, E. J., Gupta, S., Pei, X., Grant, S., Hylemon, P. B., & Dent, P. (2002) · Hepatology · doi:10.1053/jhep.2002.32533 · Cited by 144 · see citing works
Neuman, M. G., Angulo, P., Malkiewicz, I. M., Jorgensen, R. A., Shear, N. H., Dickson, E. R., Haber, J. A., Katz, G. G., & Lindor, K. D. (2002) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2002.02672.x · Cited by 142 · see citing works
Cullen, S. N., Rust, C., Fleming, K., Edwards, C., Beuers, U., & Chapman, R. W. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2007.12.023 · Cited by 136 · see citing works
Angulo, P., Dickson, E. R., Therneau, T. M., Jorgensen, R. A., Smith, C., DeSotel, C. K., Lange, S. M., Anderson, M. L., Mahoney, D. W., & Lindor, K. D. (1999) · Journal of Hepatology · doi:10.1016/s0168-8278(99)80136-6 · Cited by 134 · see citing works
Ursodeoxycholic Acid Therapy in Cystic Fibrosis—Associated Liver Disease: A Dose–Response Study
Colombo, C., Crosignani, A., Assaisso, M., Battezzati, P. M., Podda, M., Giunta, A., Zimmer-Nechemias, L., & Setchell, K. D. R. (1992) · Hepatology · doi:10.1002/hep.1840160412 · Cited by 128 · see citing works
Effect of deoxycholic acid and ursodeoxycholic acid on lipid peroxidation in cultured macrophages.
Ljubuncic, P., Fuhrman, B., Oiknine, J., Aviram, M., & Bomzon, A. (1996) · Gut · doi:10.1136/gut.39.3.475 · Cited by 119 · see citing works
Poynard, T., Zoulim, F., Ratziu, V., Degos, F., Imbert‐Bismut, F., Dény, P., Landais, P., Hasnaoui, A. E., Slama, A., Blin, P., et al. (2005) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2005.41957.x · Cited by 118 · see citing works
Antioxidant properties of ursodeoxycholic acid
Lapenna, D., Ciofani, G., Festi, D., Neri, M., Pierdomenico, S. D., Giamberardino, M. A., & Cuccurullo, F. (2002) · Biochemical Pharmacology · doi:10.1016/s0006-2952(02)01391-6 · Cited by 111 · see citing works
Effect of high-dose ursodeoxycholic acid on its biliary enrichment in primary sclerosing cholangitis
Rost, D., Rudolph, G., Kloeters-Plachky, P., & Stiehl, A. (2004) · Hepatology · doi:10.1002/hep.20370 · Cited by 84 · see citing works
Balmer, M. L., Siegrist, K., Zimmermann, A., & Dufour, J. (2009) · Liver International · doi:10.1111/j.1478-3231.2009.02037.x · Cited by 78 · see citing works
Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis
Suzuki, A., Lymp, J. F., Sauver, J. L. S., Angulo, P., & Lindor, K. D. (2006) · Liver International · doi:10.1111/j.1478-3231.2006.01362.x · Cited by 70 · see citing works
Assessing the outcome of nonalcoholic steatohepatitis? It's time to get serious†‡
Ratziu, V., & Poynard, T. (2006) · Hepatology · doi:10.1002/hep.21391 · Cited by 69 · see citing works
van de Meeberg, P. C., Houwen, R. H. J., Sinaasappel, M., Heijerman, H. G. M., Bijleveld, C. M. A., & Henegouwen, G. P. V. B. (1997) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529709007686 · Cited by 58 · see citing works
Nishigaki, Y., Ohnishi, H., Moriwaki, H., & Muto, Y. (1996) · Digestive Diseases and Sciences · doi:10.1007/bf02088577 · Cited by 46 · see citing works
Poynard, T., Ngo, Y., Marcellin, P., Hadziyannis, S. J., Ratziu, V., Benhamou, Y., & Groups, F. T. A. D. 4. A. 4. S. (2009) · Journal of Viral Hepatitis · doi:10.1111/j.1365-2893.2008.01065.x · Cited by 42 · see citing works
Pelletier, G., Roulot, D. M., Davion, T., Masliah, C., Causse, X., Oberti, F., Raabe, J., Lemmens, C. V., Labadie, H., & Serfaty, L. (2003) · Hepatology · doi:10.1053/jhep.2003.50118 · Cited by 42 · see citing works
Ursodeoxycholic Acid Modifies Gut-Derived Endotoxemia in Neonatal Rats
Schwarzenberg, S. J., & Bundy, M. V. (1994) · Pediatric Research · doi:10.1203/00006450-199402000-00018 · Cited by 30 · see citing works
Suppressive effect of ursodeoxycholic acid on type IIA phospholipase A2 expression in HepG2 cells†‡
Ikegami, T., Matsuzaki, Y., Fukushima, S., Shoda, J., Olivier, J. L., Bouscarel, B. E., & Tanaka, N. (2005) · Hepatology · doi:10.1002/hep.20630 · Cited by 29 · see citing works
Bernstein, C., Payne, C. M., Bernstein, H., & Garewal, H. S. (2002) · Pharmacology · doi:10.1159/000056179 · Cited by 26 · see citing works
Bellentani, S., Chao, Y., Ferretti, I., Panini, R., & Tiribelli, C. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0430 · Cited by 19 · see citing works
Ratziu, V., Chojkier, M., Sheikh, M. Y., Sanyal, A. J., Lim, J. K., Conjeevaram, H. S., Chalasani, N., Abdelmalek, M. F., Bakken, A., Renou, C., et al. (2010) · Journal of Hepatology · doi:10.1016/s0168-8278(10)60086-4 · Cited by 6 · see citing works
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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 · see citing works
Chalasani, 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 3,798 · see citing works
Rinella, M. E., Neuschwander-Tetri, B. A., Siddiqui, M. S., Abdelmalek, M. F., Caldwell, S., Barb, D., Kleiner, D. E., & Loomba, R. (2023) · Hepatology · doi:10.1097/hep.0000000000000323 · Cited by 2,667 · see citing works
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 · see citing works
Chalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · Gastroenterology · doi:10.1053/j.gastro.2012.04.001 · Cited by 1,770 · see citing works
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 · see citing works
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 · see citing works
Musso, G., Cassader, M., Rosina, F., & Gambino, R. (2012) · Diabetologia · doi:10.1007/s00125-011-2446-4 · Cited by 661 · see citing works
Evolving therapies for liver fibrosis
Schuppan, D., & Kim, Y. O. (2013) · Journal of Clinical Investigation · doi:10.1172/jci66028 · Cited by 596 · see citing works
Chalasani, N., Younossi, Z. M., Lavine, J. E., Diehl, A. M., Brunt, E. M., Cusi, K. J., Charlton, M., & Sanyal, A. J. (2012) · The American Journal of Gastroenterology · doi:10.1038/ajg.2012.128 · Cited by 590 · see citing works
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Jiang, C., Xie, C., Lv, Y., Li, J., Krausz, K. W., Shi, J., Brocker, C. N., Desai, D., Amin, S. G., Bisson, W. H., et al. (2015) · Nature Communications · doi:10.1038/ncomms10166 · Cited by 559 · see citing works
Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology
Fuchs, C. D., & Trauner, M. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00566-7 · Cited by 490 · see citing works
(2024) · Obesity Facts · doi:10.1159/000539371 · Cited by 510 · see citing works
Bile acid transporters and regulatory nuclear receptors in the liver and beyond
Halilbasic, E., Claudel, T., & Trauner, M. A. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.08.002 · Cited by 397 · see citing works
Castro, R. E., Ferreira, D. M. S., Afonso, M. B., Borralho, P. M., Machado, M. V., Cortez‐Pinto, H., & Rodrigues, C. M. P. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.08.008 · Cited by 351 · see citing works
From NAFLD in clinical practice to answers from guidelines
Nascimbeni, F., Pais, R., Bellentani, S., Day, C. P., Ratziu, V., Loria, P., & Lonardo, A. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.05.044 · Cited by 335 · see citing works
Kuang, J., Wang, J., Li, Y., Li, M., Zhao, M., Ge, K., Zheng, D., Cheung, K. C.-P., Liao, B., Wang, S., et al. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.07.011 · Cited by 330 · see citing works
Watanabe, S., Hashimoto, E., Ikejima, K., Uto, H., Ono, M., Sumida, Y., Seike, M., Takei, Y., Takehara, T., Tokushige, K., et al. (2015) · Journal of Gastroenterology · doi:10.1007/s00535-015-1050-7 · Cited by 326 · see citing works
Mueller, M., Thorell, A., Claudel, T., Jha, P., Köfeler, H. C., Lackner, C., Hoesel, B., Fauler, G., Stojaković, T., Einarsson, C., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2014.12.034 · Cited by 314 · see citing works
Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)
Li, R., Zou, J., Ran, W., Qi, X., Chen, Y., Cui, H., & Guo, J. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1087260 · Cited by 338 · see citing works
Gut liver brain axis in diseases: the implications for therapeutic interventions
Yan, M., Man, S., Sun, B., Ma, L., Guo, L., Huang, L., & Gao, W. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01673-4 · Cited by 301 · see citing works
Spengler, E. K., & Loomba, R. S. (2015) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2015.06.013 · Cited by 285 · see citing works
Nonalcoholic fatty liver disease: an emerging threat to obese and diabetic individuals
Masuoka, H. C., & Chalasani, N. (2013) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.12016 · Cited by 283 · see citing works
Free radical biology for medicine: learning from nonalcoholic fatty liver disease
Serviddio, G., Bellanti, F., & Vendemiale, G. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.08.174 · Cited by 269 · see citing works
Features, Diagnosis, and Treatment of Nonalcoholic Fatty Liver Disease
Torres, D. M., Williams, C. D., & Harrison, S. A. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.03.011 · Cited by 269 · see citing works
KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
Kang, S. H., Lee, H. W., Yoo, J., Cho, Y., Kim, S. U., Lee, T. H., Jang, B. K., Ahn, S. B., Ahn, S. B., Kim, H., et al. (2021) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2021.0178 · Cited by 271 · see citing works
Involvement of free radicals and oxidative stress in NAFLD/NASH
Sumida, Y., Niki, E., Naito, Y., & Yoshikawa, T. (2013) · Free Radical Research · doi:10.3109/10715762.2013.837577 · Cited by 280 · see citing works
A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
Wei, M., Huang, F., Zhao, L., Zhang, Y., Yang, W., Wang, S., Li, M., Han, X., Ge, K., Qu, C., et al. (2020) · eBioMedicine · doi:10.1016/j.ebiom.2020.102766 · Cited by 253 · see citing works
Kusaczuk, M. (2019) · Cells · doi:10.3390/cells8121471 · Cited by 244 · see citing works
Diabetes and Nonalcoholic Fatty Liver Disease: A Pathogenic Duo
Williams, K., Shackel, N. A., Gorrell, M. D., McLennan, S. V., & Twigg, S. M. (2012) · Endocrine Reviews · doi:10.1210/er.2012-1009 · Cited by 232 · see citing works
Non-alcoholic fatty liver disease: What the clinician needs to know
Machado, M. V. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i36.12956 · Cited by 209 · see citing works
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 · see citing works
Watanabe, S., Hashimoto, E., Ikejima, K., Uto, H., Ono, M., Sumida, Y., Seike, M., Takei, Y., Takehara, T., Tokushige, K., et al. (2015) · Hepatology Research · doi:10.1111/hepr.12511 · Cited by 197 · see citing works
Milić, S., & Štimac, D. (2012) · Digestive Diseases · doi:10.1159/000336669 · Cited by 191 · see citing works
Lake, A. D., Novák, P., Shipkova, P. A., Aranı́bar, N., Robertson, D. G., Reily, M. D., Lu, Z. J., Lehman‐McKeeman, L. D., & Cherrington, N. J. (2013) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2013.01.022 · Cited by 189 · see citing works
Duseja, A. K., Singh, S. P., Saraswat, V. A., Acharya, S. K., Chawla, Y. K., Chowdhury, S., Dhiman, R. K., Jayakumar, R. V., Madan, K., Misra, S. P., et al. (2015) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2015.02.006 · Cited by 186 · see citing works
Farrell, G. C., Haczeyni, F., & Chitturi, S. (2018) · Advances in Experimental Medicine and Biology · doi:10.1007/978-981-10-8684-7_3 · Cited by 178 · see citing works
Vitamin D And Nonalcoholic Fatty Liver Disease (Nafld): Is It More Than Just An Association?
Kwok, R. M., Torres, D. M., & Harrison, S. A. (2013) · Hepatology · doi:10.1002/hep.26390 · Cited by 170 · see citing works
Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis
Takahashi, Y. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i13.3777 · Cited by 161 · see citing works
Reversal of liver cirrhosis: current evidence and expectations
Jung, Y. K., & Yim, H. J. (2017) · The Korean Journal of Internal Medicine · doi:10.3904/kjim.2016.268 · Cited by 152 · see citing works
The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis
Chow, M. D., Lee, Y., & Guo, G. L. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.004 · Cited by 141 · see citing works
The role of Ursodeoxycholic acid in non-alcoholic steatohepatitis: a systematic review
Xiang, Z., Chen, Y., Ma, H., Ye, Y.-F., Zheng, L., Yang, Y., Li, Y., & Jin, X. (2013) · BMC Gastroenterology · doi:10.1186/1471-230x-13-140 · Cited by 139 · see citing works
Metabolic syndrome: A review of the role of vitamin D in mediating susceptibility and outcome
Strange, R. C. (2015) · World Journal of Diabetes · doi:10.4239/wjd.v6.i7.896 · Cited by 142 · see citing works
Han, M. A. T., Altayar, O., Hamdeh, S., Takyar, V. K., Rotman, Y., Etzion, O., Lefebvre, E. A., Safadi, R., Ratziu, V., Prokop, L. J., et al. (2018) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.06.011 · Cited by 135 · see citing works
Ferolla, S. M., Couto, C. A., Costa‐Silva, L., Armiliato, G. N. D. A., Pereira, C., Martins, F. S., Ferrari, M. L., Vilela, E. G., Tôrres, H. O. D. G., da Cunha, A. S., et al. (2016) · Nutrients · doi:10.3390/nu8070397 · Cited by 136 · see citing works
Harrison, S. A., Gunn, N., Neff, G. W., Kohli, A., Liu, L., Flyer, A., Goldkind, L., & Bisceglie, A. M. D. (2021) · Nature Communications · doi:10.1038/s41467-021-25701-5 · Cited by 131 · see citing works
Farnesoid X Receptor Signaling Shapes the Gut Microbiota and Controls Hepatic Lipid Metabolism
Zhang, L., Xie, C., Nichols, R. G., Chan, S. H. J., Jiang, C., Hao, R., Smith, P. B. W., Cai, J., Simons, M., Hatzakis, E., et al. (2016) · mSystems · doi:10.1128/msystems.00070-16 · Cited by 126 · see citing works
FXR Agonists as Therapeutic Agents for Non-alcoholic Fatty Liver Disease
Carr, R. M., & Reid, A. E. (2015) · Current Atherosclerosis Reports · doi:10.1007/s11883-015-0500-2 · Cited by 125 · see citing works
Ivashkin, V. T., Mayevskaya, M. V., Pavlov, C. S., Тихонов, И. Н., Shirokova, E. N., Buyeverov, A. O., Drapkina, O. M., Shulpekova, Y. O., Tsukanov, V. V., Mammayev, S. N., et al. (2016) · Russian Journal of Gastroenterology Hepatology Coloproctology · doi:10.22416/1382-4376-2016-26-2-24-42 · Cited by 125 · see citing works
Liver fibrosis: Common mechanisms and antifibrotic therapies
Schuppan, D. (2015) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2015.05.005 · Cited by 122 · see citing works
Nonalcoholic fatty liver disease and cardiovascular disease
Liu, H. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8407 · Cited by 119 · see citing works
Schattenberg, J. M., & Schuppan, D. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32834c7cfc · Cited by 119 · see citing works
Rodent Models of Nonalcoholic Fatty Liver Disease
Zhong, F., Zhou, X., Xu, J., & Gao, L. (2019) · Digestion · doi:10.1159/000501851 · Cited by 120 · see citing works
Bile acid and receptors: biology and drug discovery for nonalcoholic fatty liver disease
Jiao, T., Ma, Y., Guo, X., Ye, Y., & Xie, C. (2022) · Acta Pharmacologica Sinica · doi:10.1038/s41401-022-00880-z · Cited by 122 · see citing works
Ferrell, J. M., Boehme, S., Li, F., & Chiang, J. Y. L. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m064709 · Cited by 112 · see citing works
KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
(2013) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2013.19.4.325 · Cited by 114 · see citing works
Non-alcoholic fatty liver disease and insulin resistance: From bench to bedside
Gariani, K., Philippé, J., & Jornayvaz, F. R. (2012) · Diabetes & Metabolism · doi:10.1016/j.diabet.2012.11.002 · Cited by 112 · see citing works
Noureddin, M., Mato, J. M., & Lu, S. C.-L. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215579161 · Cited by 111 · see citing works
Lau, H. C.-H., Zhang, X., & Yu, J. (2025) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-025-01089-1 · Cited by 112 · see citing works
Li, S., Tan, H. Y., Wang, N., Hong, M., Li, L., Cheung, F., & Feng, Y. (2016) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2016/4305074 · Cited by 96 · see citing works
Munteanu, M., TINIAKOS, D. G., Anstee, Q. M., Charlotte, F., Marchesini, G., Bugianesi, E., Trauner, M. A., Romero‐Gómez, M., de Oliveira, C. P. M. S., Day, C. P., et al. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13770 · Cited by 95 · see citing works
Younossi, Z. M., Reyes, M. J., Mishra, A., Mehta, R., & Henry, L. L. (2013) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12543 · Cited by 92 · see citing works
Recent research trends and updates on nonalcoholic fatty liver disease
Yoo, J., Kim, W. K., Kim, M. Y., Jun, D. W., Kim, S. G., Yeon, J.-E., Lee, J. W., Cho, Y. K., Park, S. H., & Sohn, J. H. (2018) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2018.0037 · Cited by 92 · see citing works
Chen, Y.-S., Liu, H.-M., & Lee, T.-Y. (2019) · Cells · doi:10.3390/cells8030253 · Cited by 92 · see citing works
A Current Understanding of Bile Acids in Chronic Liver Disease
Farooqui, N., Elhence, A., & Shalimar, S. (2021) · Journal of Clinical and Experimental Hepatology · doi:10.1016/j.jceh.2021.08.017 · Cited by 91 · see citing works
Nonalcoholic steatohepatitis: emerging targeted therapies to optimize treatment options
Milić, S., Mikolašević, I., Zrnić, I. K., Stanić, M., Poropat, G., Štimac, D., Vlahović-Palčevski, V., & Orlić, L. (2015) · Drug Design Development and Therapy · doi:10.2147/dddt.s64877 · Cited by 91 · see citing works
Ursodeoxycholic acid accelerates bile acid enterohepatic circulation
Zhang, Y., Jiang, R., Zheng, X., Lei, S., Huang, F., Xie, G., Kwee, S. A., Yu, H., Farrar, C. E., Sun, B., et al. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14705 · Cited by 88 · see citing works
Traussnigg, S., Schattenberg, J. M., Demir, M., Wiegand, J., Geier, A., Teuber, G., Hofmann, W. P., Kremer, A. E., Spreda, F., Kluwe, J., et al. (2019) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(19)30184-0 · Cited by 88 · see citing works
Recent advances on FXR-targeting therapeutics
Panzitt, K., Zollner, G., Marschall, H., & Wagner, M. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111678 · Cited by 86 · see citing works
Pérez‐Matute, P., Pérez‐Martínez, L., Blanco, J. R., & Oteo, J. A. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/493413 · Cited by 84 · see citing works
Tsuchida, T., Shiraishi, M., Ohta, T., Sakai, K., & Ishii, S. (2011) · Metabolism · doi:10.1016/j.metabol.2011.10.023 · Cited by 84 · see citing works
Lin, S., Mao, R., Qian, C., Bettenworth, D., Wang, J., Li, J., Bruining, D. H., Jairath, V., Feagan, B. G., Chen, M., et al. (2021) · Physiological Reviews · doi:10.1152/physrev.00005.2021 · Cited by 83 · see citing works
Perspectives on Treatment for Nonalcoholic Steatohepatitis
Lassailly, G., Caiazzo, R. J., Pattou, F. N., & Mathurin, P. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.03.004 · Cited by 82 · see citing works
Pathil, A., Mueller, J., Warth, A., Chamulitrat, W., & Stremmel, W. (2011) · Hepatology · doi:10.1002/hep.25531 · Cited by 81 · see citing works
Radun, R., & Trauner, M. (2021) · Seminars in Liver Disease · doi:10.1055/s-0041-1731707 · Cited by 81 · see citing works
PNPLA3 as a therapeutic target for fatty liver disease: the evidence to date
Cherubini, A., Casirati, E., Tomasi, M., & Valenti, L. (2021) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2021.2018418 · Cited by 79 · see citing works
Nadinskaia, M. Y., Maevskaya, M. V., Ivashkin, V. T., Kodzoeva, K. B., Пирогова, И. Ю., Ev, C., Vitalevich, N. A., Kaibullayeva, J. A., Konysbekova, A., Raissova, A., et al. (2021) · World Journal of Gastroenterology · doi:10.3748/wjg.v27.i10.959 · Cited by 78 · see citing works
Ballestri, S., Nascimbeni, F., Romagnoli, D., Baldelli, E., & Lonardo, A. (2016) · Advances in Therapy · doi:10.1007/s12325-016-0306-9 · Cited by 77 · see citing works
Modern approach to the clinical management of non-alcoholic fatty liver disease
Ben, M. D. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8341 · Cited by 77 · see citing works
Antifibrotic Therapies in the Liver
Schuppan, D., & Mehal, W. Z. (2015) · Seminars in Liver Disease · doi:10.1055/s-0035-1550055 · Cited by 75 · see citing works
Pharmacological interventions for non-alcohol related fatty liver disease (NAFLD)
Lombardi, R., Onali, S., Thorburn, D., Davidson, B. R., Gurusamy, K. S., & Tsochatzis, E. A. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011640.pub2 · Cited by 74 · see citing works
Vitamin D and the vitamin D receptor in liver pathophysiology
Zúñiga, S., Firrincieli, D., Housset, C., & Chignard, N. (2011) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2011.02.003 · Cited by 73 · see citing works
A critical review of endpoints for non-cirrhotic NASH therapeutic trials
Ratziu, V. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.12.001 · Cited by 74 · see citing works
Li, H., Wang, Q., Chen, P., Zhou, C., Zhang, X., & Chen, L. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.788558 · Cited by 73 · see citing works
Dong, Y., Lv, Q., Li, S., Wu, Y., Li, L., Li, J., Zhang, F., Sun, X., & Tong, N. (2017) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2016.11.009 · Cited by 71 · see citing works
Lambert, J. E., Parnell, J. A., Eksteen, B., Raman, M., Bomhof, M. R., Rioux, K. P., Madsen, K. L., & Reimer, R. A. (2015) · BMC Gastroenterology · doi:10.1186/s12876-015-0400-5 · Cited by 73 · see citing works
Tang, Y., Zhang, J., Li, J., Lei, X., Xu, D., Wang, Y., Li, C., Li, X., & Mao, Y. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2019.05.016 · Cited by 70 · see citing works
Gerges, S. H., Wahdan, S. A., Elsherbiny, D. A., & El‐Demerdash, E. (2021) · Life Sciences · doi:10.1016/j.lfs.2021.119220 · Cited by 72 · see citing works
Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: Long-term results
Pietu, F. J., Guillaud, O., Walter, T., Vallin, M., Hervieu, V., Scoazec, J., & Dumortier, J. (2011) · Clinics and Research in Hepatology and Gastroenterology · doi:10.1016/j.clinre.2011.10.011 · Cited by 69 · see citing works
Carino, A., Biagioli, M., Marchianò, S., Fiorucci, C., Zampella, A., Monti, M. C., Scarpelli, P. T., Ricci, P., Distrutti, E., & Fiorucci, S. (2019) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2019.07.006 · Cited by 68 · see citing works
Nonalcoholic Fatty Liver Disease
Paredes, A. H., Torres, D. M., & Harrison, S. A. (2012) · Clinics in Liver Disease · doi:10.1016/j.cld.2012.03.005 · Cited by 68 · see citing works
A Comprehensive Updated Review of Pharmaceutical and Nonpharmaceutical Treatment for NAFLD
Hossain, N., Kanwar, P., & Mohanty, S. R. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/7109270 · Cited by 68 · see citing works
Pediatric Nonalcoholic Fatty Liver Disease
Bozic, M. A., Subbarao, G. C., & Molleston, J. P. (2013) · Nutrition in Clinical Practice · doi:10.1177/0884533613489153 · Cited by 67 · see citing works
Current Treatment Options for Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis
Beaton, M. D. (2012) · Canadian Journal of Gastroenterology · doi:10.1155/2012/725468 · Cited by 69 · see citing works
Ursodeoxycholic Acid Ameliorates Fructose-Induced Metabolic Syndrome in Rats
Mahmoud, A. A. A., & Elshazly, S. M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106993 · Cited by 66 · see citing works
Greuter, T., Malhi, H., Gores, G. J., & Shah, V. H. (2017) · JCI Insight · doi:10.1172/jci.insight.95354 · Cited by 67 · see citing works
Hu, J., Wei, H., Yao, K., Zhu, X., Chen, Z., & Ye, L. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i12.1492 · Cited by 65 · see citing works
Ratziu, V., Cadranel, J., Serfaty, L., Denis, J., Renou, C., Delasalle, P., Bernhardt, C., & Perlemuter, G. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.03.019 · Cited by 62 · see citing works
Nonalcoholic Fatty Liver Disease and the Metabolic Syndrome
Rahimi, R. S., & Landaverde, C. E. (2013) · Nutrition in Clinical Practice · doi:10.1177/0884533612470464 · Cited by 61 · see citing works
Maevskaya, M. V., Kotovskaya, Y. V., Ivashkin, V. T., Ткачева, О. Н., Troshina, E. A., Shestakova, M. V., Breder, V. V., Geyvandova, N. I., Doshchitsin, V. L., Dudinskaya, Е. N., et al. (2022) · Terapevticheskii arkhiv · doi:10.26442/00403660.2022.02.201363 · Cited by 65 · see citing works
- Authors
- Ratziu, V., de Ledinghen, V., Oberti, F., Mathurin, P., Wartelle-Bladou, C., Renou, C., Sogni, P., Maynard, M., Larrey, D., Serfaty, L., Bonnefont-Rousselot, D., Bastard, J.-P., Rivière, M., & Spénard, J.
- Affiliations
- Inserm (FR)
- Centre Hospitalier Universitaire d'Angers (FR)
- Hôpital Claude Huriez (FR)
- Hôpital Cochin (FR)
- Hospices Civils de Lyon (FR)
- Centre Hospitalier Universitaire de Montpellier (FR)
- Hôpital Saint-Antoine (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Université de Montréal (CA)
- Corresponding author
- Ratziu, Vlad
- ORCID
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 54
- Issue
- 5
- Pages
- 1011-1019
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2078519195
- Cited by
- 338
- References
- 58
- Citations by year
- 2026: 10 · 2025: 20 · 2024: 24 · 2023: 21 · 2022: 18 · 2021: 26 · 2020: 13 · 2019: 25 · 2018: 14 · 2017: 18 · 2016: 18 · 2015: 32 · 2014: 22 · 2013: 33 · 2012: 33
- FWCI
- 17.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Axcan Pharma Inc
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nonalcoholic steatohepatitis, ursodeoxycholic acid, alanine aminotransferase normalization, liver fibrosis, liver inflammation, insulin resistance, glycemic control, FibroTest, bile acid therapy
- MeSH terms
- Adult, Blood Glucose, Cholagogues and Choleretics, Dose-Response Relationship, Drug, Fatty Liver, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Insulin, Insulin Resistance, Male, Middle Aged, Ursodeoxycholic Acid, Treatment Outcome, Non-alcoholic Fatty Liver Disease
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