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The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids
Open accessAbstract
The histologic spectrum of nonalcoholic fatty liver disease (NAFLD) includes fatty liver (NAFL) and steatohepatitis (NASH), which can progress to cirrhosis in up to 20% of NASH patients. Bile acids (BA) are linked to the pathogenesis and therapy of NASH. We (1) characterized the plasma BA profile in biopsy‐proven NAFL and NASH and compared to controls and (2) related the plasma BA profile to liver histologic features, disease activity, and fibrosis. Liquid chromatography/mass spectrometry quantified BAs. Descriptive statistics, paired and multiple group comparisons, and regression analyses were performed. Of 86 patients (24 controls, 25 NAFL, and 37 NASH; mean age 51.8 years and body mass index 31.9 kg/m 2), 66% were women. Increased total primary BAs and decreased secondary BAs (both P < 0.05) characterized NASH. Total conjugated primary BAs were significantly higher in NASH versus NAFL (P = 0.047) and versus controls (P < 0.0001). NASH had higher conjugated to unconjugated chenodeoxycholate (P = 0.04), cholate (P = 0.0004), and total primary BAs (P < 0.0001). The total cholate to chenodeoxycholate ratio was significantly higher in NAFLD without (P = 0.005) and with (P = 0.02) diabetes. Increased key BAs were associated with higher grades of steatosis (taurocholate), lobular (glycocholate) and portal inflammation (taurolithocholate), and hepatocyte ballooning (taurocholate). Conjugated cholate and taurocholate directly and secondary to primary BA ratio inversely correlated to NAFLD activity score. A higher ratio of total secondary to primary BA decreased (odds ratio, 0.57; P = 0.004) and higher conjugated cholate increased the likelihood of significant fibrosis (F≥2) (P = 0.007). Conclusion: NAFLD is associated with significantly altered circulating BA composition, likely unaffected by type 2 diabetes, and correlated with histological features of NASH; these observations provide the foundation for future hypothesis‐driven studies of specific effects of BAs on specific aspects of NASH. (H epatology 2018;67:534‐548).
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“These BA (DCA, TCDCA, GCDCA) are significantly increased in patients with NASH [247].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [247]
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“Increased circulating DCA levels have been found in patients with NASH [247].”
From Gut-pancreas-liver Axis as a target for treatment of NAFLD/NASH (2020) · cites this paper as [247]
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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-citationDonnelly, K. L., Smith, C. I., Schwarzenberg, S. J., Jessurun, J., Boldt, M. D., & Parks, E. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23621 · Cited by 3,604
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
Bile salt biotransformations by human intestinal bacteria
Ridlon, J. M., Kang, D.-J., & Hylemon, P. B. (2006) · Journal of Lipid Research · doi:10.1194/jlr.r500013-jlr200 · Cited by 2,829
Self-citationIdentification 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
Nonalcoholic Fatty Liver Disease
Rinella, M. E. (2015) · JAMA · doi:10.1001/jama.2015.5370 · Cited by 2,320
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., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61933-4 · Cited by 2,237
Self-citationNonalcoholic 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
Self-citationTGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.001 · Cited by 1,885
Wong, R. J., Aguilar, M. E. F., Cheung, R. C., Perumpail, R. B., Harrison, S. A., Younossi, Z. M., & Ahmed, A. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.11.039 · Cited by 1,861
Role of Bile Acids and Bile Acid Receptors in Metabolic Regulation
Lefebvre, P., Cariou, B., Lien, F., Kuipers, F., & Staels, B. (2009) · Physiological Reviews · doi:10.1152/physrev.00010.2008 · Cited by 1,678
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
Boursier, J., Mueller, O., Barret, M., Machado, M., Fizanne, L., Araujo‐Perez, F., Guy, C. D., Seed, P. C., Rawls, J. F., David, L. A., et al. (2016) · Hepatology · doi:10.1002/hep.28356 · Cited by 1,483 · cited 8×
“While changes in the intestinal microbiome have been reported in NASH,(24-27) they do not yet provide mechanistic information regarding the linkage of these changes with development of NASH.”
BackgroundInfluentialPotential of fecal microbiota for early-stage detection of colorectal cancer
Zeller, G., Tap, J., Voigt, A. Y., Sunagawa, S., Kultima, J. R., Costea, P. I., Amiot, A., Böhm, J., Brunetti, F., Habermann, N., et al. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145645 · Cited by 1,375
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 · cited 1×
“Over the last decade, BAs have been shown to play a central role in metabolic homeostasis and to affect insulin sensitivity.((8,9)) The insulin-sensitizing effects of BAs are mediated through interaction with their receptor, FXR.”
BackgroundSelf-citationKatsuma, S., Hirasawa, A., & Tsujimoto, G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.139 · Cited by 789
White, D. L., Kanwal, F., & El–Serag, H. B. (2012) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2012.10.001 · Cited by 766
Pellicciari, R., Fiorucci, S., Camaioni, E., Clerici, C., Costantino, G., Maloney, P. R., Morelli, A., Parks, D. J., & Willson, T. M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm025529g · Cited by 743
Bile acid receptors as targets for drug development
Schaap, F. G., Trauner, M., & Jansen, P. L. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.151 · Cited by 696
Raman, M., Ahmed, I., Gillevet, P. M., Probert, C. S., Ratcliffe, N. M., Smith, S., Greenwood, R., Sikaroodi, M., Lam, V., Crotty, P., et al. (2013) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2013.02.015 · Cited by 672
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
Beyond intestinal soap—bile acids in metabolic control
Kuipers, F., Bloks, V. W., & Groen, A. K. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.60 · Cited by 462
Human Insulin Resistance Is Associated With Increased Plasma Levels of 12α-Hydroxylated Bile Acids
Haeusler, R. A., Astiarraga, B., Camastra, S., Accili, D., & Ferrannini, E. (2013) · Diabetes · doi:10.2337/db13-0639 · Cited by 444
Wang, B., Jiang, X., Cao, M., Ge, J., Bao, Q., Tang, L., Chen, Y., & Li, L. (2016) · Scientific Reports · doi:10.1038/srep32002 · Cited by 390
Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease
Mouzaki, M., Wang, A. Y., Bandsma, R., Comelli, E. M., Arendt, B. M., Zhang, L., Fung, S., Fischer, S. E., McGilvray, I. G., & Allard, J. P. (2016) · PLOS ONE · doi:10.1371/journal.pone.0151829 · Cited by 385
Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis
Ferslew, B. C., Xie, G., Johnston, C., Su, M., Stewart, P. W., Jia, W. P., Brouwer, K. L. R., & Barritt, A. S. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3776-8 · Cited by 347
Hepatocellular ballooning in NASH
Caldwell, S. H., Ikura, Y., Dias, D., Isomoto, K., Yabu, A., Moskaluk, C. A., Pramoonjago, P., Simmons, W., Scruggs, H., Rosenbaum, N., et al. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.04.031 · Cited by 250
Copple, B. L., & Li, T. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.12.007 · Cited by 238
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
Bechmann, L. P., Kocabayoglu, P., Sowa, J., Sydor, S., Best, J., Schlattjan, M., Beilfuss, A., Schmitt, J., Hannivoort, R. A., Kılıçarslan, A., et al. (2013) · Hepatology · doi:10.1002/hep.26225 · Cited by 235
Kumar, D. P., Rajagopal, S., Mahavadi, S., Mirshahi, F., Grider, J. R., Murthy, K. S., & Sanyal, A. J. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.09.104 · Cited by 206
Self-citationImpaired Generation of 12-Hydroxylated Bile Acids Links Hepatic Insulin Signaling with Dyslipidemia
Haeusler, R. A., Pratt–Hyatt, M., Welch, C. L., Klaassen, C. D., & Accili, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.11.010 · Cited by 157
Ridlon, J. M., & Hylemon, P. B. (2011) · Journal of Lipid Research · doi:10.1194/jlr.m020313 · Cited by 151
Self-citationWewalka, M., Patti, M., Barbato, C., Houten, S. M., & Goldfine, A. B. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-3367 · Cited by 135
Dutia, R., Embrey, M., O'Brien, S. A., Haeusler, R. A., Agenor, K., Homel, P., McGinty, J., Vincent, R. P., Alaghband-Zadeh, J., Staels, B., et al. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.1 · Cited by 95
Hansen, M., Scheltema, M. J. V., Sonne, D. P., Hansen, J. S., Sperling, M., Rehfeld, J. F., Holst, J. J., Vilsbøll, T., & Knop, F. K. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12648 · Cited by 95
Hirano, S., & Masuda, N. (1982) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38052-4 · Cited by 57
Bhowmik, S., Chiu, H., Jones, D. H., Chiu, H., Miller, M. D., Xu, Q., Farr, C. L., Ridlon, J. M., Wells, J. E., Elsliger, M., et al. (2015) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24971 · Cited by 53
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Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943
Zhang, X., Coker, O. O., Chu, E. S., Fu, K., Lau, H. C. H., Wang, Y.-X., Chan, A. W. H., Wei, H., Yang, X., Sung, J. J. Y., et al. (2021) · Gut · doi:10.1136/gutjnl-2019-319664 · Cited by 841
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Watt, M. J., Miotto, P. M., De Nardo, W., & Montgomery, M. K. (2019) · Endocrine Reviews · doi:10.1210/er.2019-00034 · Cited by 615
Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy
Chiang, J. Y. L., & Ferrell, J. M. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00223.2019 · Cited by 580
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Metadata
- Authors
- Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., Kumar, D. P., Kohli, R., Zhou, H., Hylemon, P. B., Contos, M. J., Idowu, M., & Sanyal, A. J.
- Affiliations
- Virginia Commonwealth University (US)
- Venebio (United States) (US)
- University of Southern California (US)
- Corresponding author
- Puri, Puneet
- ORCID
- Venue
- Hepatology
- Published
- 2017-12-23
- Volume
- 67
- Issue
- 2
- Pages
- 534-548
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC5764808
- OpenAlex
- W2735896722
- Cited by
- 426
- References
- 38
- Citations by year
- 2026: 34 · 2025: 52 · 2024: 59 · 2023: 42 · 2022: 55 · 2021: 69 · 2020: 40 · 2019: 39 · 2018: 31 · 2017: 4
- FWCI
- 24.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Bristol-Myers Squibb
- GlaxoSmithKline
- American Association for the Study of Liver Diseases
- Gilead Sciences
- National Institutes of Health (R01 DK 10596‐01, UL1TR000058)
- National Institute on Alcohol Abuse and Alcoholism (K23AA021179)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK105961, R01DK100314, T32DK007150, R01DK081410, P30DK048522)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, bile acids, chenodeoxycholic acid, cholic acid, taurocholate, liver fibrosis, steatosis, liver histopathology, NAFLD activity score, type 2 diabetes, hepatocyte ballooning, inflammation, cirrhosis risk, biomarkers
- MeSH terms
- Receptor, Farnesoid X-Activated, Adult, Aged, Bile Acids and Salts, Cross-Sectional Studies, Female, Humans, Liver Cirrhosis, Male, Middle Aged, Prospective Studies, Severity of Illness Index, Receptors, Cytoplasmic and Nuclear, Non-alcoholic Fatty Liver Disease
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