High‐dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double‐blind, randomized, placebo‐controlled trial†
Abstract
UNLABELLED: In uncontrolled clinical studies, ursodeoxycholic acid (UDCA) had a beneficial effect on nonalcoholic steatohepatitis (NASH). However, a large controlled trial using UDCA (13-15 mg/kg/day) was unable to confirm these results. Accordingly, a randomized, placebo-controlled study was initiated with a high dose of UDCA (23-28 mg/kg/day). The allocation of patients and the evaluation of liver histology were performed according to a modified Brunt score and the nonalcoholic fatty liver disease activity score (NAS). With the modified Brunt score, 185 patients with histologically proven NASH were randomized [intention to treat (ITT)], and 147 were treated per protocol (PP). With the NAS, 137 patients were confirmed to have NASH, 48 had borderline NASH, and 1 did not have NASH. The treatment time was 18 months. At entry, the treatment groups were comparable. A second biopsy sample was obtained from 139 of 185 patients (NAS: 107/137). The primary criterion for evaluation was a change in the liver histology; the secondary criteria were single histological variables and liver biochemistry. Significant differences in the overall histology could not be detected between the two treatment groups with the modified Brunt score (P = 0.881) or NAS (P = 0.355). Only lobular inflammation improved significantly (P for the modified Brunt score = 0.011, P for NAS = 0.005). In subgroup analyses, significant improvements in lobular inflammation were also observed in males, younger patients up to 50 years of age, slightly overweight patients, and patients with hypertension and an increased histology score. The fibrosis score did not change (P for ITT = 0.133, P for PP = 0.140). With the exception of gamma-glutamyl transferase, UDCA did not improve laboratory data. CONCLUSION: High-dose UDCA failed to improve the overall histology in patients with NASH in comparison with placebo.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
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 [374]
Despite limitations and methodological differences, there is a strong indication of biochemical efficacy (ALT reduction) and a good safety profile for UDCA, but no proof of histological efficacy.
“Despite several limitations and methodological differences, there is a strong indication of biochemical effi cacy (ALT reduction) and a good safety pro fi le, but no proof of histological ef fi cacy.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [374]
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
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Nissen, S. E., & Wolski, K. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa072761 · Cited by 4,675 · see citing works
Nonalcoholic Steatohepatitis: A Proposal for Grading and Staging The Histological Lesions
Brunt, E. M., Janney, C. G., Di Bisceglie, A. M., Neuschwander-Tetri, B. A., & Bacon, B. R. (1999) · American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.01377.x · Cited by 3,907 · see citing works
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity.
MATTEONI, C., YOUNOSSI, Z., GRAMLICH, T., BOPARAI, N., LIU, Y., & MCCULLOUGH, A. (1999) · Gastroenterology · doi:10.1016/s0016-5085(99)70506-8 · Cited by 3,345 · see citing works
Nonalcoholic Fatty Liver, Steatohepatitis, and the Metabolic Syndrome
Marchesini, G., Bugianesi, E., Forlani, G., Cerrelli, F., Lenzi, M., Manini, R., Natale, S., Vanni, E., Villanova, N., Melchionda, N., et al. (2003) · Hepatology · doi:10.1053/jhep.2003.50161 · Cited by 2,676 · see citing works
Sampling Variability of Liver Biopsy in Nonalcoholic Fatty Liver Disease
Ratziu, V., Charlotte, F., Heurtier, A., Gombert, S., Giral, P., Bruckert, E., Grimaldi, A., Capron, F., & Poynard, T. (2005) · Gastroenterology · doi:10.1053/j.gastro.2005.03.084 · Cited by 2,106 · see citing works
Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities
Sanyal, A. J., Campbell–Sargent, C., Mirshahi, F., Rizzo, W. B., Contos, M. J., Sterling, R. K., Luketic, V. A., Shiffman, M. L., & Clore, J. N. (2001) · Gastroenterology · doi:10.1053/gast.2001.23256 · Cited by 2,078 · see citing works
A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis
Belfort, R., Harrison, S. A., Brown, K., Darland, C., Finch, J., Hardies, J., Balas, B., Gastaldelli, A., Tio, F., Pulcini, J., et al. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa060326 · Cited by 1,827 · see citing works
Bugianesi, E., Leone, N., Vanni, E., Marchesini, G., Brunello, F., CARUCCI, P., Musso, A., Paolis, P. D., Capussotti, L., Salizzoni, M., et al. (2002) · Gastroenterology · doi:10.1053/gast.2002.34168 · Cited by 1,436 · see citing works
Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia
Després, J.-P., Golay, A., & Sjöström, L. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa044537 · Cited by 1,392 · see citing works
Schwab, M. (2011) · Springer eBooks · doi:10.1007/978-3-642-16483-5_4730 · Cited by 1,241 · see citing works
Osei‐Hyiaman, D., DePetrillo, M. A., Pacher, P., Liu, J., Radaeva, S., Bátkai, S., Harvey-White, J. D., Mackie, K., Offertáler, L., Wang, L., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23057 · Cited by 1,103 · see citing works
Lindor, K. D., Gershwin, E. M., Poupon, R., Kaplan, M., Bergasa, N. V., & Heathcote, J. E. (2009) · Hepatology · doi:10.1002/hep.22906 · Cited by 1,099 · see citing works
Adams, L. A., Sanderson, S. O., Lindor, K. D., & Angulo, P. (2004) · Journal of Hepatology · doi:10.1016/j.jhep.2004.09.012 · Cited by 908 · see citing works
Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis
Harrison, S. A., Torgerson, S., Hayashi, P. H., Ward, J. A., & Schenker, S. (2003) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2003.08699.x · Cited by 728 · 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
A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis
Promrat, K., Lutchman, G., Uwaifo, G. I., Freedman, R. J., Soza, A., Heller, T., Doo, E., Ghany, M., Premkumar, A., Park, Y., et al. (2004) · Hepatology · doi:10.1002/hep.20012 · Cited by 726 · see citing works
Crespo, J., Cayón, A., Fernández-Gil, P. L., Hernández‐Guerra, M., Mayorga, M., Domínguez‐Díez, A., Fernández-Escalante, J. C., & Pons‐Romero, F. (2001) · Hepatology · doi:10.1053/jhep.2001.29628 · Cited by 693 · 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
Hepatic effects of dietary weight loss in morbidly obese subjects
Andersen, T., Gluud, C. N., Franzmann, M., & Christoffersen, P. (1991) · Journal of Hepatology · doi:10.1016/0168-8278(91)90942-5 · Cited by 405 · 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
Merriman, R. B., Ferrell, L. D., Patti, M. G., Weston, S. R., Pabst, M. S., Aouizerat, B. E., & Bass, N. M. (2006) · Hepatology · doi:10.1002/hep.21346 · Cited by 326 · see citing works
Hirschfield, G. M., & Heathcote, E. J. (2010) · Wiley eBooks · doi:10.1002/9781444314403.ch32 · Cited by 260 · see citing works
Plasma adiponectin is decreased in nonalcoholic fatty liver disease
Pagano, C., Soardo, G., Esposito, W., Fallo, F., Basan, L., Donnini, D., Federspil, G., Sechi, L. A., & Vettor, R. (2005) · European Journal of Endocrinology · doi:10.1530/eje.1.01821 · Cited by 257 · see citing works
The effects of discontinuing pioglitazone in patients with nonalcoholic steatohepatitis†
Lutchman, G. A., Modi, A. A., Kleiner, D. E., Promrat, K., Heller, T., Ghany, M. G., Borg, B. B., Loomba, R. S., Liang, T. J., Premkumar, A., et al. (2007) · Hepatology · doi:10.1002/hep.21661 · Cited by 240 · see citing works
Angulo, P. (2010) · Hepatology · doi:10.1002/hep.23521 · Cited by 232 · see citing works
Betaine for nonalcoholic fatty liver disease
Abdelmalek, M. F., Sanderson, S. O., Angulo, P., Soldevila‐Pico, C., Liu, C., Peter, J. A., Keach, J. C., Cave, M. C., Chen, T., McClain, C. J., et al. (2009) · Hepatology · doi:10.1002/hep.23239 · Cited by 225 · see citing works
Ursodeoxycholic Acid and Atorvastatin in the Treatment of Nonalcoholic Steatohepatitis
Kıyıcı, M., Gülten, M., Gurel, S., Nak, S. G., Dolar, E., Savcı, G., Adım, Ş. B., Yerci, Ö., & Memik, F. (2003) · Canadian Journal of Gastroenterology · doi:10.1155/2003/857869 · Cited by 199 · see citing works
Satapathy, S. K., Garg, S., Chauhan, R., Sakhuja, P., Malhotra, V., Sharma, B. C., & Sarin, S. K. (2004) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2004.40220.x · Cited by 198 · 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
Merat, S., Malekzadeh, R., Sohrabi, M., Sotoudeh, M., Rakhshani, N., Sohrabpour, A. A., & Nasseri‐Moghaddam, S. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(02)00441-5 · Cited by 129 · see citing works
4-Hydroxynonenal as a selective pro-fibrogenic stimulus for activated human hepatic stellate cells
Zamara, E., Novo, E., Marra, F., Gentilini, A., Romanelli, R. G., Caligiuri, A., Robino, G., Tamagno, E., Aragno, M., Danni, O., et al. (2003) · Journal of Hepatology · doi:10.1016/s0168-8278(03)00480-x · Cited by 123 · see citing works
Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis
Toshio, F., Fukushima, J., Shiga, J., Takahashi, Y., NAKANO, T., Maeyama, S., Masayuki, U., Ohbu, M., Matsumoto, T., & Matsumoto, K. (2005) · Hepatology Research · doi:10.1016/j.hepres.2005.09.018 · Cited by 74 · see citing works
Bellentani, S. (2005) · European Journal of Gastroenterology & Hepatology · doi:10.1097/00042737-200502000-00001 · Cited by 47 · see citing works
Angulo, P. G. (2010) · Hepatology · doi:10.1002/hep.23677 · Cited by 13 · see citing works
Ratziu, V., de Lédinghen, V., Oberti, F., Mathurin, P., Wartelle‐Bladou, C., Renou, C., & Spénard, J. (2009) · Journal of Hepatology · doi:10.1016/s0168-8278(09)60049-0 · Cited by 7 · see citing works
Flagged first, then by citations
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 · see citing works
EASL–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 · 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 3,805 · 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
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548 · 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 1,773 · see citing works
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 · 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
EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease
European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), & European Association for the Study of Obesity (EASO) (2016) · Diabetologia · doi:10.1007/s00125-016-3902-y · Cited by 685 · 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
Bile 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 · 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 592 · see citing works
EASL-EASD-EASO Clinical Practice Guidelines for the Management of Non-Alcoholic Fatty Liver Disease
European Association for the Study of the Liver (EASL), E. A. F. T. S. O. D. (. (2016) · Obesity Facts · doi:10.1159/000443344 · Cited by 522 · 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
Takaki, A., Kawai, D., & Yamamoto, K. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms141020704 · Cited by 452 · see citing works
NASH is an Infl ammatory Disorder: Pathogenic, Prognostic and Therapeutic Implications
Farrell, G. C., Rooyen, D. M. V., Gan, L. T., & Chitturi, S. (2012) · Gut and Liver · doi:10.5009/gnl.2012.6.2.149 · Cited by 396 · see citing works
A randomized controlled trial of high-dose ursodesoxycholic acid for nonalcoholic steatohepatitis
Ratziu, V., de Ledinghen, V., Oberti, F., Mathurin, P., Wartelle-Bladou, C., Renou, C., Sogni, P., Maynard, M., Larrey, D., Serfaty, L., et al. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.08.030 · Cited by 338 · see citing works
Muzurović, E. M., Mikhailidis, D. P., & Mantzoros, C. S. (2021) · Metabolism · doi:10.1016/j.metabol.2021.154770 · Cited by 339 · 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
Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment
Smith, B. W., & Adams, L. A. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.72 · Cited by 327 · see citing works
The role of oxidative stress in non-alcoholic steatohepatitis
Koek, G. H., Liedorp, P. R., & Bast, A. (2011) · Clinica Chimica Acta · doi:10.1016/j.cca.2011.04.013 · Cited by 315 · 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
Kleiner, D. E., & Makhlouf, H. R. (2016) · Clinics in Liver Disease · doi:10.1016/j.cld.2015.10.011 · Cited by 303 · see citing works
Non-alcoholic fatty liver disease
Smith, B. W., & Adams, L. A. (2011) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2011.596521 · Cited by 288 · see citing works
A concise review of non-alcoholic fatty liver disease
Than, N. N., & Newsome, P. N. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.01.001 · Cited by 289 · 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
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
Tokushige, K., Ikejima, K., Ono, M., Eguchi, Y., Kamada, Y., Itoh, Y., Akuta, N., Yoneda, M., Iwasa, M., Yoneda, M., et al. (2021) · Journal of Gastroenterology · doi:10.1007/s00535-021-01796-x · Cited by 276 · 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
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
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
Yilmaz, Y. N. (2012) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12046 · Cited by 217 · see citing works
Intestinal microbiome and NAFLD: molecular insights and therapeutic perspectives
Hu, H., Lin, A., Kong, M., Yao, X., Yin, M., Xia, H., Ma, J., & Liu, H. (2019) · Journal of Gastroenterology · doi:10.1007/s00535-019-01649-8 · Cited by 208 · see citing works
Prevalence and risk factors for non‐alcoholic fatty liver disease in Asian people who are not obese
Liu, C. (2012) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2012.07222.x · Cited by 207 · see citing works
Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications
Roma, M. G., Toledo, F. D., Boaglio, A. C., Basiglio, C. L., Crocenzi, F. A., & Pozzi, E. J. S. (2011) · Clinical Science · doi:10.1042/cs20110184 · Cited by 207 · 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
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
Non-alcoholic fatty liver disease in 2015
Ahmed∥, M. (2015) · World Journal of Hepatology · doi:10.4254/wjh.v7.i11.1450 · Cited by 176 · 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
Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground
Chitturi, S., Wong, V. W., & Farrell, G. C. (2011) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2010.06548.x · Cited by 161 · see citing works
Revision and update on clinical practice guideline for liver cirrhosis
Suk, K. T., Baik, S. K., Yoon, J., Cheong, J. Y., Paik, Y. H., Lee, C. H., Kim, Y. S., Lee, J. W., Kim, D. J., Cho, S. W., et al. (2012) · The Korean Journal of Hepatology · doi:10.3350/kjhep.2012.18.1.1 · Cited by 141 · see citing works
Lazebnik, L. B., Голованова, Е. В., Туркина, С. В., Raikhelson, K. L., Okovityy, S. V., Drapkina, O. M., Maev, I. V., Ai, M., Ройтберг, Г. Е., Khlynova, O. V., et al. (2021) · Экспериментальная и клиническая гастроэнтерология · doi:10.31146/1682-8658-ecg-185-1-4-52 · Cited by 155 · see citing works
The unfolded protein response and hepatic lipid metabolism in non alcoholic fatty liver disease
Song, M. J., & Malhi, H. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107401 · Cited by 142 · 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
Tokushige, K., Ikejima, K., Ono, M., Eguchi, Y., Kamada, Y., Itoh, Y., Akuta, N., Yoneda, M., Iwasa, M., Yoneda, M., et al. (2021) · Hepatology Research · doi:10.1111/hepr.13688 · Cited by 145 · 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
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
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
Metabolic Spectrum of Liver Failure in Type 2 Diabetes and Obesity: From NAFLD to NASH to HCC
Kim, H.-M., Lee, D. S., An, T. H., Park, H., Kim, W. K., Bae, K., & Oh, K. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094495 · Cited by 130 · see citing works
Molecular Mechanisms and New Treatment Strategies for Non-Alcoholic Steatohepatitis (NASH)
Takaki, A., Kawai, D., & Yamamoto, K. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15057352 · Cited by 126 · see citing works
Leite, N. C. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i26.8377 · Cited by 123 · 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
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
Treatment efficacy of a probiotic preparation for non‐alcoholic steatohepatitis: A pilot trial
Манжалій, Е., Virchenko, O., Falalyeyeva, T. M., Beregova, T. V., & Stremmel, W. (2017) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12561 · Cited by 118 · see citing works
Kotb, M. A. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms13078882 · Cited by 114 · 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: An update with special focus on the role of gut microbiota
Doulberis, M., Kotronis, G., Gialamprinou, D., Kountouras, J., & Katsinelos, P. (2017) · Metabolism · doi:10.1016/j.metabol.2017.03.013 · Cited by 113 · see citing works
Noureddin, M., Mato, J. M., & Lu, S. C.-L. (2015) · Experimental Biology and Medicine · doi:10.1177/1535370215579161 · Cited by 109 · see citing works
Liao, Z., Sun, B., Zhang, Q., Jia, L., Wei, Y., Liang, M., & Xu, H. (2020) · Aquaculture · doi:10.1016/j.aquaculture.2020.734935 · Cited by 104 · 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
Current therapeutic strategies in non‐alcoholic fatty liver disease
Dowman, J. K., Armstrong, M. J., Tomlinson, J., & Newsome, P. N. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01403.x · Cited by 100 · see citing works
Endocrine causes of nonalcoholic fatty liver disease
Marino, L. (2015) · World Journal of Gastroenterology · doi:10.3748/wjg.v21.i39.11053 · Cited by 92 · 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
Mechanisms Linking Nonalcoholic Fatty Liver Disease with Coronary Artery Disease
Nseir, W., Shalata, A., Marmor, A. T., & Assy, N. (2011) · Digestive Diseases and Sciences · doi:10.1007/s10620-011-1767-y · 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
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
Self-citationUrsodeoxycholic 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
Nonalcoholic Fatty Liver Disease, Diabetes Mellitus and Cardiovascular Disease: Newer Data
Mavrogiannaki, A. N., & Migdalis, I. N. (2013) · International Journal of Endocrinology · doi:10.1155/2013/450639 · Cited by 87 · see citing works
Kim, D. J., Yoon, S., Ji, S. C., Yang, J., Kim, Y., Lee, S., Yu, K., Jang, I., Chung, J., & Cho, J. (2018) · Scientific Reports · doi:10.1038/s41598-018-30349-1 · Cited by 87 · 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
Specific bile acids inhibit hepatic fatty acid uptake in mice
Nie, B., Park, H. M., Kazantzis, M., Lin, M., Henkin, A. H., Ng, S. M., Song, S., Chen, Y., Tran, H., Lai, R., et al. (2012) · Hepatology · doi:10.1002/hep.25797 · 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
Fang, H., Lacerda, R. R. E., Barra, N. G., Zada, D. K., Robin, N., Mehra, A., & Schertzer, J. D. (2024) · Endocrine Reviews · doi:10.1210/endrev/bnae025 · Cited by 81 · see citing works
Pathogenesis and therapeutic approaches for non-alcoholic fatty liver disease
Yoon, H. (2014) · World Journal of Hepatology · doi:10.4254/wjh.v6.i11.800 · Cited by 75 · 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
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
Lee, B., Lee, Y., Park, C., Rhee, E., Lee, W., Kim, N. H., Choi, K. M., Park, K., Choi, Y., Soo, B., et al. (2020) · Diabetes & Metabolism Journal · doi:10.4093/dmj.2020.0010 · Cited by 77 · 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
Kim, M. Y., Cho, M.-Y., Baik, S. K., Jeong, P. H., Suk, K. T., Jang, Y. O., Yea, C. J., Kim, J. W., Kim, H. S., Kwon, S. O., et al. (2012) · Liver International · doi:10.1111/j.1478-3231.2012.02774.x · Cited by 71 · see citing works
Paul, J. (2020) · Egyptian Liver Journal · doi:10.1186/s43066-020-00043-x · Cited by 69 · 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
Placebo effect on progression and regression in NASH: Evidence from a meta‐analysis
Ng, C. H., Xiao, J., Lim, W. H., Chin, Y. H., Yong, J. N., Tan, D. J. H., Tay, P., Syn, N., Foo, R., Chan, M., et al. (2022) · Hepatology · doi:10.1002/hep.32315 · Cited by 69 · 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
Mahjoubin‐Tehran, M., Vincentis, A. D., Mikhailidis, D. P., Atkin, S. L., Mantzoros, C. S., Jamialahmadi, T., & Sahebkar, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101049 · Cited by 70 · 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
Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review
Arab, J. P. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i34.12182 · Cited by 65 · see citing works
Current and emerging pharmacotherapeutic interventions for the treatment of liver fibrosis
Lambrecht, J., van Grunsven, L. A., & Tacke, F. (2020) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2020.1774553 · Cited by 64 · see citing works
- Authors
- Leuschner, U. F. H., Lindenthal, B., Herrmann, G., Arnold, J. C., Rössle, M., Cordes, H., Zeuzem, S., Hein, J., & Berg, T.
- Affiliations
- Krankenhaus Sachsenhausen (DE)
- Goethe University Frankfurt (DE)
- Klinikum Ludwigsburg (DE)
- Agaplesion Diakonieklinikum Rotenburg (DE)
- University Hospital Leipzig (DE)
- Corresponding author
- Leuschner, Ulrich F. H.
- Venue
- Hepatology
- Published
- 2010-08
- Volume
- 52
- Issue
- 2
- Pages
- 472-479
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W2097677758
- Cited by
- 317
- References
- 36
- Citations by year
- 2026: 9 · 2025: 7 · 2024: 13 · 2023: 14 · 2022: 15 · 2021: 29 · 2020: 17 · 2019: 25 · 2018: 15 · 2017: 21 · 2016: 20 · 2015: 25 · 2014: 23 · 2013: 25 · 2012: 25
- FWCI
- 19.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- 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
- ursodeoxycholic acid, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, liver histopathology, lobular inflammation, liver fibrosis, liver biochemistry, gamma-glutamyl transferase
- MeSH terms
- Adolescent, Adult, Aged, Double-Blind Method, Fatty Liver, Female, Humans, Male, Middle Aged, Ursodeoxycholic Acid, Young Adult
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
