The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Chronic intermittent hypoxia is a major trigger for non-alcoholic fatty liver disease in morbid obese
Abstract
Background & aims Morbid obesity is frequently associated with low grade systemic inflammation, increased macrophage accumulation in adipose tissue (AT), obstructive sleep apnea (OSA), and nonalcoholic fatty liver disease (NAFLD). It has been suggested that chronic intermittent hypoxia (CIH) resulting from OSA could be an independent factor for early stage of NAFLD in addition to other well-recognized factors (dyslipidemia or insulin resistance). Moreover, macrophage accumulation in AT is associated with local hypoxia in fat tissue. We hypothesized that the association between CIH and morbid obesity could exert additional specific deleterious effects both in the liver and adipose tissues.Methods One hundred and one morbidly obese subjects were prospectively recruited and underwent bariatric surgery during which a liver needle biopsy as well as surgical subcutaneous and omental AT biopsies were obtained. Oxygen desaturation index (ODI) quantified the severity of nocturnal CIH.Results Histopathologic analysis of liver biopsies demonstrated that NAFLD lesions (ballooning of hepatocytes, lobular inflammation), NAFLD activity score (NAS), and fibrosis were significantly more severe in patients with the highest ODI tertile (p values ≤0.001 for all hepatic lesions). In multivariate analysis, after adjustment for age, obesity, and insulin resistance status, CIH remained independently associated with hepatic fibrosis, fibroinflammation, and NAS. By contrast, no association was found between CIH, macrophage accumulation, and adipocytes size in both subcutaneous and omental adipose tissue.Conclusions In morbidly obese patients, CIH was strongly associated with more severe liver injuries but did not worsen obesity induced macrophage accumulation in adipose tissue depots.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“Both OSA and PCOS are associated with MASLD,”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [65]
In the citing paper
“and several studies suggest OSA is also associated with more advanced MASLD/MASH histology, 64,65”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [65]
Citations
Cites
The Occurrence of Sleep-Disordered Breathing among Middle-Aged Adults
Young, T., Palta, M., Dempsey, J., Skatrud, J., Weber, S., & Badr, S. (1993) · New England Journal of Medicine · doi:10.1056/nejm199304293281704 · Cited by 10,183
Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Kopelman, P. G. (2000) · Nature · doi:10.1038/35007508 · Cited by 4,795
Steatohepatitis: A tale of two “hits”?
Day, C. P., & James, O. F. W. (1998) · Gastroenterology · doi:10.1016/s0016-5085(98)70599-2 · Cited by 4,285
McNicholas, W. T., Strohl, K. P., White, D. P., Levy, P. A., Schmidt, W., Wheatley, J. R., Redline, S. S., Carley, D. W., Buysse, D. J., Young, T. B., et al. (1999) · PubMed · Cited by 3,665
Nonalcoholic Fatty Liver Disease: From Steatosis to Cirrhosis
Farrell, G. C., & Larter, C. Z. (2006) · Hepatology · doi:10.1002/hep.20973 · Cited by 2,428
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
Visceral fat adipokine secretion is associated with systemic inflammation in obese humans
Fontana, L., Eagon, J. C., Trujillo, M. E., Scherer, P. E., & Klein, S. (2007) · Diabetes · doi:10.2337/db06-1656 · Cited by 1,417
Adipose Tissue Hypoxia in Obesity and Its Impact on Adipocytokine Dysregulation
Hosogai, N., Fukuhara, A., Oshima, K., Miyata, Y., Tanaka, S., Segawa, K., Furukawa, S., Tochino, Y., Komuro, R., Matsuda, M., et al. (2007) · Diabetes · doi:10.2337/db06-0911 · Cited by 1,257 · cited 1×
“In obese mice, local hypoxia appears to dysregulate adipocytokines expression [53].”
BackgroundPunjabi, N. M. (2004) · American Journal of Epidemiology · doi:10.1093/aje/kwh261 · Cited by 1,107
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077
Pepperell, J., Ramdassingh-Dow, S., Crosthwaite, N., Mullins, R., Jenkinson, C., Stradling, J. R., & Davies, R. J. O. (2002) · The Lancet · doi:10.1016/s0140-6736(02)07445-7 · Cited by 1,055
The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Utzschneider, K. M., & Kahn, S. E. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0587 · Cited by 874
Jenkinson, C., Davies, R. J., Mullins, R., & Stradling, J. R. (1999) · The Lancet · doi:10.1016/s0140-6736(98)10532-9 · Cited by 826
The Epidemiology of Nonalcoholic Fatty Liver Disease in Adults
Clark, J. (2006) · Journal of Clinical Gastroenterology · doi:10.1097/01.mcg.0000168638.84840.ff · Cited by 804
Reduced Adipose Tissue Oxygenation in Human Obesity
Pasarica, M., Sereda, O. R., Redman, L. M., Albarado, D. C., Hymel, D. T., Roan, L. E., Rood, J. C., Burk, D. H., & Smith, S. R. (2009) · Diabetes · doi:10.2337/db08-1098 · Cited by 786
Fracanzani, A. L., Valenti, L. V. C., Bugianesi, E., Andreoletti, M., Colli, A., Vanni, E., Bertelli, C., Fatta, E., Bignamini, D., Marchesini, G., et al. (2008) · Hepatology · doi:10.1002/hep.22429 · Cited by 716
Metformin reverses fatty liver disease in obese, leptin-deficient mice.
Lin, H. Z., Yang, S. Q., Chuckaree, C., Kuhajda, F., Ronnet, G., & Diehl, A. M. (2000) · Nature Medicine · doi:10.1038/79697 · Cited by 673
van der Poorten, D., Milner, K., Hui, J. M., Hodge, A. D., Trenell, M. I., Kench, J. G., London, R. M., Peduto, T., Chisholm, D. J., & George, J. (2008) · Hepatology · doi:10.1002/hep.22350 · Cited by 611
Cancello, R., Tordjman, J., Poitou, C., Guilhem, G., Bouillot, J. L., Hugol, D., Coussieu, C., Basdevant, A., Hen, A. B., Bedossa, P., et al. (2006) · Diabetes · doi:10.2337/db06-0133 · Cited by 607
Obstructive Sleep Apnea Among Obese Patients With Type 2 Diabetes
Foster, G. D., Sanders, M. H., Millman, R., Zammit, G., Borradaile, K. E., Newman, A. B., Wadden, T. A., Kelley, D., Wing, R. R., Pi Sunyer, F. X., et al. (2009) · Diabetes Care · doi:10.2337/dc08-1776 · Cited by 600
Mathurin, P., Hollebecque, A., Arnalsteen, L., Buob, D., Leteurtre, E., Caiazzo, R. J., Pigeyre, M., Verkindt, H., Dharancy, S., Louvet, A., et al. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.04.052 · Cited by 490
Natural history of nonalcoholic steatohepatitis: A longitudinal study of repeat liver biopsies
Fassio, E., �lvarez, E., Dom�nguez, N., Landeira, G., & Longo, C. (2004) · Hepatology · doi:10.1002/hep.20410 · Cited by 470
Sleep-disordered Breathing and Cardiovascular Disease
Punjabi, N. M., Newman, A. B., Young, T. B., Resnick, H. E., & SANDERS, M. H. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200712-1884oc · Cited by 383
Aron‐Wisnewsky, J., Tordjman, J., Poitou, C., Darakhshan, F., Hugol, D., Basdevant, A., Aissat, A., Guerre-Millo, M., & Clément, K. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0925 · Cited by 379
Tamisier, R., Pépin, J. L., Rémy, J., Baguet, J. P., Taylor, J. A., Weiss, J. W., & Lévy, P. (2011) · European Respiratory Journal · doi:10.1183/09031936.00204209 · Cited by 323
Predictors of Nonalcoholic Steatohepatitis and Advanced Fibrosis in Morbidly Obese Patients
Ong, J. P., Elariny, H. A., Collantes, R. S., Younoszai, A., Chandhoke, V., Reines, H. D., Goodman, Z. D., & Younossi, Z. M. (2005) · Obesity Surgery · doi:10.1381/0960892053576820 · Cited by 322
Nonalcoholic Fatty Liver Disease in Severely Obese Subjects
Gholam, P. M., Flancbaum, L., Machan, J. T., Charney, D. A., & Kotler, D. P. (2007) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.01041.x · Cited by 296
The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome
Çiftçi, T. U., Köktürk, O., Bukan, N. C., & Bi̇lgi̇han, A. (2004) · Cytokine · doi:10.1016/j.cyto.2004.07.003 · Cited by 280
Predictors of long-term compliance with continuous positive airway pressure
Kohler, M., Smith, D., Tippett, V., & Stradling, J. R. (2010) · Thorax · doi:10.1136/thx.2010.135848 · Cited by 275
Chronic intermittent hypoxia predisposes to liver injury†
Savransky, V., Nanayakkara, A., Vivero, A., Li, J., Bevans‐Fonti, S., Smith, P. L., Torbenson, M. S., & Polotsky, V. Y. (2007) · Hepatology · doi:10.1002/hep.21593 · Cited by 262
Chronic liver injury during obstructive sleep apnea†
Tanné, F., Gagnadoux, F., Chazouillères, O., Fleury, B., Wendum, D., Lasnier, E., Lebeau, B., Poupon, R. Y., & Serfaty, L. (2005) · Hepatology · doi:10.1002/hep.20725 · Cited by 238
Obstructive Sleep Apnea, Insulin Resistance, and Steatohepatitis in Severe Obesity
Polotsky, V. Y., Patil, S. P., Savransky, V., Laffan, A. M., Bevans‐Fonti, S., Frame, L. A., Steele, K., Schweizter, M. A., Clark, J. M., Torbenson, M. S., et al. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200804-608oc · Cited by 218
Kunde, S. S., Lazenby, A. J., Clements, R. H., & Abrams, G. A. (2005) · Hepatology · doi:10.1002/hep.20818 · Cited by 215
The Impact of Obesity on Oxygen Desaturation during Sleep-disordered Breathing
Peppard, P. E., Ward, N. R., & Morrell, M. J. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200905-0773oc · Cited by 194
Intermittent Hypoxia Induces Early Functional Cardiovascular Remodeling in Mice
Dematteis, M., Julien, C., Guillermet, C., Sturm, N., Lantuejoul, S., Mallaret, M., Lévy, P., & Gozal, E. (2008) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200702-238oc · Cited by 167
Peripheral Neuropathy in Sleep Apnea: A Tissue Marker of the Severity of Nocturnal Desaturation
Mayer, P., Demattéis, M., Pépin, J., Wuyam, B., Veale, D., Vila, A., & Levy, P. A. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.159.1.9709051 · Cited by 123
The prevalence of retinopathy in men with Type 2 diabetes and obstructive sleep apnoea
West, S. D., Groves, D. C., Lipinski, H., Nicoll, D., Mason, R. H., Scanlon, P. H., & Stradling, J. R. (2010) · Diabetic Medicine · doi:10.1111/j.1464-5491.2010.02962.x · Cited by 114
Tordjman, J., Poitou, C., Hugol, D., Bouillot, J., Basdevant, A., Bédossa, P., Guerre-Millo, M., & Clément, K. (2009) · Journal of Hepatology · doi:10.1016/j.jhep.2009.02.031 · Cited by 107
Jouët, P., Sabaté, J., Maillard, D., Msika, S., Mechler, C., Ledoux, S., Harnois, F., & Coffin, B. (2007) · Obesity Surgery · doi:10.1007/s11695-007-9085-3 · Cited by 89
Night-to-night variation of the oxygen desaturation index in sleep apnoea syndrome
Fietze, I., Dingli, K., Diefenbach, K., Douglas, N. J., Glos, M., Tallafuss, M., Terhalle, W., & Witt, C. M. (2004) · European Respiratory Journal · doi:10.1183/09031936.04.00100203 · Cited by 86
Hypoxia aggravates non-alcoholic steatohepatitis in mice lacking hepatocellular PTEN
Piguet, A., Stroka, D., Zimmermann, A., & Dufour, J. (2009) · Clinical Science · doi:10.1042/cs20090313 · Cited by 79
Liver Enzymes and Histology in Obese Patients With Obstructive Sleep Apnea
Kallwitz, E. R., Herdegen, J. J., Madura, J., Jakate, S. M., & Cotler, S. J. (2007) · Journal of Clinical Gastroenterology · doi:10.1097/01.mcg.0000225692.62121.55 · Cited by 78
Hepatic Complications of Obesity
Diehl, A. M. (2010) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2009.12.001 · Cited by 76
Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea
Baguet, J. P., Barone‐Rochette, G., Levy, P. A., Vautrin, E., Pierre, H., Ormezzano, O., & Pépin, J. (2010) · European Respiratory Journal · doi:10.1183/09031936.00165709 · Cited by 67
Steiropoulos, P., Παπάνας, Ν., Nena, E., Antoniadou, M., Serasli, E., Papoti, S., Hatzizisi, O., Kyriazis, G., Τzouvelekis, Α., Maltezos, E. S., et al. (2010) · Mediators of Inflammation · doi:10.1155/2010/675320 · Cited by 66
Effects of obstructive sleep apnea syndrome on hepatic steatosis and nonalcoholic steatohepatitis
Tatsumi, K., & Saibara, T. (2005) · Hepatology Research · doi:10.1016/j.hepres.2005.09.014 · Cited by 65
Inducible Nitric Oxide Distribution in the Fatty Liver of a Mouse with High Fat Diet-Induced Obesity
Ha, S.-K., & Chae, C. (2010) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.59.595 · Cited by 62
Genetic polymorphisms of interleukin-6 modulate fibrosis progression in mild chronic hepatitis C
Falleti, E., Fabris, C., Vandelli, C., Colletta, C., Cussigh, A., Smirne, C., Fontanini, E., Cmet, S., Minisini, R., Bitetto, D., et al. (2010) · Human Immunology · doi:10.1016/j.humimm.2010.06.006 · Cited by 41
Hypoxia and non-alcoholic fatty liver disease
Byrne, C. D. (2009) · Clinical Science · doi:10.1042/cs20090565 · Cited by 32
Hepatic Complications of Obesity
Diehl, A. M. (2005) · Gastroenterology Clinics of North America · doi:10.1016/j.gtc.2004.12.012 · Cited by 28
Body mass index and risk of liver cirrhosis in middle aged UK women: Prospective study
Naveau, S. (2010) · Gastroentérologie Clinique et Biologique · doi:10.1016/j.gcb.2010.05.003 · Cited by 9
Sleep Study Predictors of Prevalent Cardiovascular Disease
Stradling, J. R. (2009) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.179.3.254 · Cited by 1
Cited by
Sorted by citations
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
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
Fibrosis and adipose tissue dysfunction.
Sun, K., Tordjman, J., Clément, K., & Scherer, P. E. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.06.016 · Cited by 960
Drager, L. F., Togeiro, S. M., Polotsky, V. Y., & Lorenzi-Filho, G. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.05.045 · Cited by 886
Non-alcoholic fatty liver disease: An expanded review
Benedict, M., & Zhang, X. (2017) · World Journal of Hepatology · doi:10.4254/wjh.v9.i16.715 · Cited by 788
Metadata
- Authors
- Aron-Wisnewsky, J., Minville, C., Tordjman, J., Lévy, P., Bouillot, J.-L., Basdevant, A., Bedossa, P., Clément, K., & Pépin, J.-L.
- Affiliations
- Inserm (FR)
- Hôpital Cochin (FR)
- Corresponding author
- Pépin, Jean-Louis
- Venue
- Journal of Hepatology
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 56
- Issue
- 1
- Pages
- 225-233
- ISSN
- 0168-8278 (ISSN-L)
- OpenAlex
- W2020505247
- Cited by
- 255
- References
- 55
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 19 · 2023: 14 · 2022: 21 · 2021: 16 · 2020: 15 · 2019: 18 · 2018: 18 · 2017: 13 · 2016: 19 · 2015: 25 · 2014: 24 · 2013: 20 · 2012: 10
- FWCI
- 13.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Physiology (medical) › Obstructive Sleep Apnea Research
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- chronic intermittent hypoxia, non-alcoholic fatty liver disease, morbid obesity, obstructive sleep apnea, liver fibrosis, hepatic steatosis, oxygen desaturation index, bariatric surgery, liver biopsy, NAFLD activity score, fibroinflammation
- MeSH terms
- Adipose Tissue, Adult, Hypoxia, Chronic Disease, Fatty Liver, Female, Humans, Insulin Resistance, Liver, Male, Middle Aged, Obesity, Morbid, Prospective Studies, Risk Factors, Cohort Studies, Sleep Apnea, Obstructive, Bariatric Surgery, 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
