Transmembrane 6 superfamily member 2 gene variant disentangles nonalcoholic steatohepatitis from cardiovascular disease
Open accessAbstract
Excess hepatic storage of triglycerides is considered a benign condition, but nonalcoholic steatohepatitis (NASH) may progress to fibrosis and promote atherosclerosis. Carriers of the TM6SF2 E167K variant have fatty liver as a result of reduced secretion of very‐low‐density lipoproteins (VLDLs). As a result, they have lower circulating lipids and reduced risk of myocardial infarction. In this study, we aimed to assess whether TM6SF2 E167K affects liver damage and cardiovascular outcomes in subjects at risk of NASH. Liver damage was evaluated in 1,201 patients who underwent liver biopsy for suspected NASH; 427 were evaluated for carotid atherosclerosis. Cardiovascular outcomes were assessed in 1,819 controls from the Swedish Obese Subjects (SOS) cohort. Presence of the inherited TM6SF2 E167K variant was determined by TaqMan assays. In the liver biopsy cohort, 188 subjects (13%) were carriers of the E167K variant. They had lower serum lipid levels than noncarriers (P < 0.05), had more‐severe steatosis, necroinflammation, ballooning, and fibrosis (P < 0.05), and were more likely to have NASH (odds ratio [OR]: 1.84; 95% confidence interval [CI]: 1.23‐2.79) and advanced fibrosis (OR, 2.08; 95% CI: 1.20‐3.55), after adjustment for age, sex, body mass index, fasting hyperglycemia, and the I148M PNPLA3 risk variant. However, E167K carriers had lower risk of developing carotid plaques (OR, 0.49; 95% CI: 0.25‐0.94). In the SOS cohort, E167K carriers had higher alanine aminotransferase ALT and lower lipid levels (P < 0.05), as well as a lower incidence of cardiovascular events (hazard ratio: 0.61; 95% CI: 0.39‐0.95). Conclusions: Carriers of the TM6SF2 E167K variant are more susceptible to progressive NASH, but are protected against cardiovascular disease. Our findings suggest that reduced ability to export VLDLs is deleterious for the liver. (H epatology 2015;61:506‐514)
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The TM6SF2 rs58542926 minor allele is reportedly associated with MASLD and sometimes MASH.
“The rs58542926 minor allele of transmembrane 6 superfamily member 2 (TM6SF2) is also reportedly associated with MASLD and sometimes MASH (134, 140-142).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [141]
The HSD17B13 splice variant rs72613567 is protective against MASH, and HSD17B13 may contribute to MASH fibrosis by promoting pyrimidine catabolism.
“Furthermore, the splice variant rs72613567 in the Hydroxysteroid 17-beta Dehydrogenase 13 (HSD17B13) gene has been identified as protective against MASH, with HSD17B13 potentially contributing to MASH fibrosis by promoting pyrimidine catabolism (134, 140-142).”
From Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH) (2023) · cites this paper as [141]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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
Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease
Romeo, S., Kozlitina, J., Xing, C., Pertsemlidis, A., Cox, D., Pennacchio, L. A., Boerwinkle, E., Cohen, J. C., & Hobbs, H. H. (2008) · Nature Genetics · doi:10.1038/ng.257 · Cited by 3,416 · see citing works
Self-citationNonalcoholic Fatty Liver Disease
Marchesini, G., Brizi, M., Bianchi, G., Tomassetti, S., Bugianesi, E., Lenzi, M., McCullough, A. J., Natale, S., Forlani, G., & Melchionda, N. (2001) · Diabetes · doi:10.2337/diabetes.50.8.1844 · Cited by 2,581 · see citing works
Risk of Cardiovascular Disease in Patients with Nonalcoholic Fatty Liver Disease
Targher, G., Day, C. P., & Bonora, E. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0912063 · Cited by 1,907 · 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
Musso, G., Gambino, R., Cassader, M., & Pagano, G. (2010) · Annals of Medicine · doi:10.3109/07853890.2010.518623 · Cited by 1,285 · see citing works
Kozlitina, J., Smagris, E., Stender, S., Nordestgaard, B. G., Zhou, H. H., Tybjærg-Hansen, A., Vogt, T. F., Hobbs, H. H., & Cohen, J. C. (2014) · Nature Genetics · doi:10.1038/ng.2901 · Cited by 1,234 · see citing works
Yamaguchi, K., Yang, L., McCall, S. J., Huang, J., Yu, X. X., Pandey, S., Bhanot, S., Monia, B. P., Li, Y.-X., & Diehl, A. M. (2007) · Hepatology · doi:10.1002/hep.21655 · Cited by 1,019 · see citing works
Speliotes, E. K., Yerges-Armstrong, L. M., Wu, J., Hernaez, R., Kim, L. J., Palmer, C. D., Gudnason, V., Eiriksdottir, G., Garcia, M. E., Launer, L. J., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1001324 · Cited by 984 · see citing works
Sookoian, S. C., & Pirola, C. J. (2011) · Hepatology · doi:10.1002/hep.24283 · Cited by 917 · see citing works
Bariatric surgery and prevention of type 2 diabetes in Swedish obese subjects
Carlsson, L. M. S., Peltonen, M., Ahlin, S., Anveden, Å., Bouchard, C., Carlsson, B., Jacobson, P., Lönroth, H., Maglio, C., Näslund, I., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1112082 · Cited by 794 · see citing works
Self-citationCuchel, M., Meagher, E. A., du Toit Theron, H., Blom, D. J., Marais, A. D., Hegele, R. A., Averna, M. R., Sirtori, C. R., Shah, P. K., Gaudet, D., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(12)61731-0 · Cited by 744 · see citing works
Fracanzani, A., Valenti, L. N., 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 692 · see citing works
Self-citationFabbrini, E., Mohammed, B. S., Magkos, F., Korenblat, K. M., Patterson, B. W., & Klein, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2007.11.038 · Cited by 631 · see citing works
Liu, Y.-L., Reeves, H. L., Burt, A. D., Tiniakos, D., McPherson, S., Leathart, J. B. S., Allison, M. E. D., Alexander, G. J., Piguet, A.-C., Anty, R., et al. (2014) · Nature Communications · doi:10.1038/ncomms5309 · Cited by 623 · see citing works
Mitochondrial free cholesterol loading sensitizes to TNF- and Fas-mediated steatohepatitis
Marı́, M., Caballero, F. G., Colell, A., Morales, A., Caballería, J., Fernandez, A., Enrich, C., Fernández-Checa, J. C., & García‐Ruiz, C. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.07.006 · Cited by 605 · see citing works
Korenblat, K. M., Fabbrini, E., Mohammed, B. S., & Klein, S. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.01.075 · Cited by 592 · see citing works
Peters, S. A. E., den Ruijter, H. M., Bots, M. L., & Moons, K. G. M. (2011) · Heart · doi:10.1136/heartjnl-2011-300747 · Cited by 412 · see citing works
Cholesterol metabolism and the pathogenesis of non-alcoholic steatohepatitis
Musso, G., Gambino, R., & Cassader, M. (2012) · Progress in Lipid Research · doi:10.1016/j.plipres.2012.11.002 · Cited by 410 · see citing works
Day, C. P. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.017 · Cited by 393 · see citing works
Mahdessian, H., Taxiarchis, A., Popov, S., Silveira, A., Franco-Cereceda, A., Hamsten, A., Eriksson, P., & van't Hooft, F. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1323785111 · Cited by 369 · see citing works
Ethnic differences in hepatic steatosis
Guerrero, R., Vega, G. L., Grundy, S. M., & Browning, J. D. (2008) · Hepatology · doi:10.1002/hep.22726 · Cited by 365 · see citing works
Holmen, O. L., Zhang, H., Fan, Y., Hovelson, D. H., Schmidt, E. M., Zhou, W., Guo, Y., Zhang, J., Langhammer, A., Løchen, M., et al. (2014) · Nature Genetics · doi:10.1038/ng.2926 · Cited by 302 · see citing works
Pirazzi, C., Adiels, M., Burza, M. A., Mancina, R. M., Levin, M. C., Ståhlman, M., Taskinen, M., Orho‐Melander, M., Perman, J., Pujia, A., et al. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.07.030 · Cited by 300 · see citing works
Self-citationValenti, L. V. C., Alisi, A., Galmozzi, E., Bartuli, A., Menico, B. D., Alterio, A., Dongiovanni, P., Fargion, S. R., & Nobili, V. (2010) · Hepatology · doi:10.1002/hep.23823 · Cited by 288 · see citing works
Self-citationChalasani, N., Wilson, L., Kleiner, D. E., Cummings, O. W., Brunt, E. M., & Ünalp, A. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.01.016 · Cited by 251 · see citing works
Dongiovanni, P., Anstee, Q. M., & Valenti, L. V. C. (2013) · Current Pharmaceutical Design · doi:10.2174/13816128113199990381 · Cited by 231 · see citing works
Self-citationCarotid Artery Intima-media Thickness in Nonalcoholic Fatty Liver Disease
Fracanzani, A. L., Burdick, L., Raselli, S., Pedotti, P., Grigore, L., Santorelli, G., Valenti, L. V. C., Maraschi, A., Catapano, A. L., & Fargion, S. R. (2008) · The American Journal of Medicine · doi:10.1016/j.amjmed.2007.08.041 · Cited by 208 · see citing works
Self-citationComparison of Liver Fat Indices for the Diagnosis of Hepatic Steatosis and Insulin Resistance
KAHL, S., Straßburger, K., Nowotny, B., Livingstone, R. S., Klüppelholz, B., Keßel, K., Hwang, J., Giani, G., Hoffmann, B. H., Pacini, G., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0094059 · Cited by 166 · see citing works
Petta, S., Miele, L., Bugianesi, E., Cammà, C., Rosso, C., Boccia, S., Cabibi, D., Marco, V. D., Grimaudo, S., Grieco, A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087523 · Cited by 151 · see citing works
Self-citationSantos, R. D., Duell, P. B., East, C. A., Guyton, J. R., Moriarty, P. M., Chin, W., & Mittleman, R. S. (2013) · European Heart Journal · doi:10.1093/eurheartj/eht549 · Cited by 144 · see citing works
PNPLA3 mediates hepatocyte triacylglycerol remodeling
Ruhanen, H., Perttilä, J., Hölttä‐Vuori, M., Zhou, Y., Yki‐Järvinen, H., Ikonen, E., Käkelä, R., & Olkkonen, V. M. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m046607 · Cited by 114 · see citing works
Gorden, A., Yang, R., Yerges‐Armstrong, L. M., Ryan, K. A., Speliotes, E. K., Borecki, I. B., Harris, T. B., Chu, X., Wood, G. C., Still, C. D., et al. (2013) · Human Heredity · doi:10.1159/000346195 · Cited by 91 · see citing works
PNPLA3 GG Genotype and Carotid Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease
Petta, S., Valenti, L. V. C., Marchesini, G., Marco, V. D., Licata, A., Cammà, C., Barcellona, M. R., Cabibi, D., Donati, B., Fracanzani, A. L., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074089 · Cited by 84 · see citing works
Self-citationValenti, L. V. C., Nobili, V., Al‐Serri, A., Rametta, R., Leathart, J. B. S., Zappa, M. A., Dongiovanni, P., Fracanzani, A. L., Alterio, A., Roviaro, G., et al. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2011.03.035 · Cited by 81 · see citing works
Self-citationCefalu, A. B., Pirruccello, J. P., Noto, D., Gabriel, S., Valenti, V., Gupta, N., Spina, R., Tarugi, P., Kathiresan, S., & Averna, M. R. (2013) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.112.301101 · Cited by 81 · see citing works
Desmosterol in Human Nonalcoholic Steatohepatitis
Simonen, M., Männistö, V., Leppänen, J., Kamińska, D., Kärjä, V. J., Venesmaa, S., Käkelä, P., Kuusisto, J., Gylling, H., Laakso, M., et al. (2013) · Hepatology · doi:10.1002/hep.26342 · Cited by 48 · see citing works
Self-citation
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
The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD)
Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016) · Metabolism · doi:10.1016/j.metabol.2015.12.012 · Cited by 3,119 · see citing works
Visceral and ectopic fat, atherosclerosis, and cardiometabolic disease: a position statement
Neeland, I. J., Ross, R., Després, J.-P., Matsuzawa, Y., Yamashita, S., Shai, I., Seidell, J., Magni, P., Santos, R. D., Arsenault, B., et al. (2019) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30084-1 · Cited by 1,603 · see citing works
From NASH to HCC: current concepts and future challenges
Anstee, Q. M., Reeves, H. L., Kotsiliti, E., Govaere, O., & Heikenwalder, M. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0145-7 · Cited by 1,392 · see citing works
Mitochondrial dynamics in health and disease: mechanisms and potential targets
Chen, W., Zhao, H., & Li, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01547-9 · Cited by 1,306 · see citing works
Adams, L. A., Anstee, Q. M., Tilg, H., & Targher, G. (2017) · Gut · doi:10.1136/gutjnl-2017-313884 · Cited by 1,210 · see citing works
Triggering and resolution of inflammation in NASH
Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943 · see citing works
Nonalcoholic fatty liver disease
Brunt, E., Wong, V., Nobili, V., Day, C., Sookoian, S., Maher, J., Bugianesi, E., Sirlin, C., Neuschwander-Tetri, B., & Rinella, M. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.80 · Cited by 591 · see citing works
Self-citationGenetics and epigenetics of NAFLD and NASH: Clinical impact
Eslam, M., Valenti, L., & Romeo, S. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.09.003 · Cited by 971 · see citing works
Self-citationMancina, R. M., Dongiovanni, P., Petta, S., Pingitore, P., Meroni, M., Rametta, R., Borén, J., Montalcini, T., Pujia, A., Wiklund, O., et al. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.032 · Cited by 676 · see citing works
Self-citationEASL–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
Cobbina, E., & Akhlaghi, F. (2017) · Drug Metabolism Reviews · doi:10.1080/03602532.2017.1293683 · Cited by 660 · see citing works
Metabolic-associated fatty liver disease and lipoprotein metabolism
Heeren, J., & Scheja, L. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2021.101238 · Cited by 666 · see citing works
NAFLD and cardiovascular diseases: a clinical review
Kasper, P., Martin, A., Lang, S., Kütting, F., Goeser, T., Demir, M., & Steffen, H. (2020) · Clinical Research in Cardiology · doi:10.1007/s00392-020-01709-7 · Cited by 670 · see citing works
Nonalcoholic Fatty Liver Disease: Pathogenesis and Disease Spectrum
Hardy, T., Oakley, F., Anstee, Q. M., & Day, C. P. (2016) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-012615-044224 · Cited by 619 · see citing works
Recent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573 · see citing works
Buch, S., Stickel, F., Trépo, E., Way, M., Herrmann, A., Nischalke, H. D., Brosch, M., Rosendahl, J., Berg, T., Ridinger, M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3417 · Cited by 565 · see citing works
Dysregulated lipid metabolism links NAFLD to cardiovascular disease
Deprince, A., Haas, J. T., & Staels, B. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101092 · Cited by 558 · see citing works
The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis
Saponaro, C., Gaggini, M., Carli, F., & Gastaldelli, A. (2015) · Nutrients · doi:10.3390/nu7115475 · Cited by 531 · 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
The Role of Cholesterol in the Pathogenesis of NASH
Ioannou, G. N. (2016) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2015.11.008 · Cited by 498 · see citing works
From NASH to diabetes and from diabetes to NASH: Mechanisms and treatment options
Gastaldelli, A., & Cusi, K. (2019) · JHEP Reports · doi:10.1016/j.jhepr.2019.07.002 · Cited by 455 · see citing works
Role of Insulin Resistance in MAFLD
Sakurai, Y., Kubota, N., Yamauchi, T., & Kadowaki, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22084156 · Cited by 448 · see citing works
Nonalcoholic Fatty Liver Disease and the Heart
Stahl, E. P., Dhindsa, D. S., Lee, S. K., Sandesara, P. B., Chalasani, N., & Sperling, L. S. (2019) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.11.050 · Cited by 445 · see citing works
Update on NAFLD genetics: From new variants to the clinic
Trépo, E., & Valenti, L. (2020) · Journal of Hepatology · doi:10.1016/j.jhep.2020.02.020 · Cited by 393 · see citing works
Self-citationStatin use and non-alcoholic steatohepatitis in at risk individuals
Dongiovanni, P., Petta, S., Mannisto, V., Mancina, R. M., Pipitone, R., Karja, V., Maggioni, M., Kakela, P., Wiklund, O., Mozzi, E., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.05.006 · Cited by 390 · see citing works
Self-citationManagement of NAFLD: a stage-based approach
Rinella, M. E., & Sanyal, A. J. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.3 · Cited by 388 · see citing works
Distinct but complementary contributions of PPAR isotypes to energy homeostasis
Dubois, V., Eeckhoute, J., Lefèbvre, P., & Staels, B. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88894 · Cited by 385 · see citing works
Bianco, C., Jamialahmadi, O., Pelusi, S., Baselli, G., Dongiovanni, P., Zanoni, I., Santoro, L., Maier, S., Liguori, A., Meroni, M., et al. (2021) · Journal of Hepatology · doi:10.1016/j.jhep.2020.11.024 · Cited by 385 · see citing works
Self-citationAzzu, V., Vacca, M., Virtue, S., Allison, M., & Vidal-Puig, A. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.12.054 · Cited by 369 · see citing works
Dongiovanni, P., Stender, S., Pietrelli, A., Mancina, R. M., Cespiati, A., Petta, S., Pelusi, S., Pingitore, P., Badiali, S., Maggioni, M., et al. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12719 · Cited by 367 · see citing works
Self-citationKim, D., & Kim, W. R. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2016.08.028 · Cited by 341 · see citing works
Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans
Pafili, K., & Roden, M. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101122 · Cited by 330 · 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
NAFLD in children: new genes, new diagnostic modalities and new drugs
Nobili, V., Alisi, A., Valenti, L. V. C., Miele, L., Feldstein, A. E., & Alkhouri, N. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0169-z · Cited by 311 · see citing works
Self-citationGenetic contributions to NAFLD: leveraging shared genetics to uncover systems biology
Eslam, M., & George, J. (2019) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-019-0212-0 · Cited by 310 · see citing works
Metabolic Dysfunction–Associated Steatotic Liver Disease
Targher, G., Valenti, L., & Byrne, C. D. (2025) · New England Journal of Medicine · doi:10.1056/nejmra2412865 · Cited by 325 · see citing works
Self-citationAISF position paper on nonalcoholic fatty liver disease (NAFLD): Updates and future directions
Lonardo, A., Nascimbeni, F., Targher, G., Bernardi, M., Bonino, F., Bugianesi, E., Casini, A., Gastaldelli, A., Marchesini, G., Marra, F., et al. (2017) · Digestive and Liver Disease · doi:10.1016/j.dld.2017.01.147 · Cited by 306 · see citing works
Self-citationNon-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors
Juanola, O., Martínez‐López, S., Francés, R., & Gómez‐Hurtado, I. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18105227 · Cited by 303 · see citing works
Marchesini, G., Petta, S., & Grave, R. D. (2015) · Hepatology · doi:10.1002/hep.28392 · Cited by 291 · see citing works
Self-citationA 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
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
MBOAT7 rs641738 variant and hepatocellular carcinoma in non-cirrhotic individuals
Donati, B., Dongiovanni, P., Romeo, S., Meroni, M., McCain, M. V., Miele, L., Petta, S., Maier, S., Rosso, C., Luca, L. D., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-04991-0 · Cited by 262 · see citing works
Self-citationGenetic Factors That Affect Risk of Alcoholic and Nonalcoholic Fatty Liver Disease
Anstee, Q. M., Seth, D., & Day, C. P. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.01.037 · Cited by 252 · see citing works
Pipitone, R. M., Ciccioli, C., Infantino, G., Mantia, C. L., Parisi, S., Tulone, A., Pennisi, G., Grimaudo, S., & Petta, S. (2023) · Therapeutic Advances in Endocrinology and Metabolism · doi:10.1177/20420188221145549 · Cited by 239 · see citing works
Self-citationNon-alcoholic fatty liver disease and risk of cardiovascular disease
Lonardo, A., Sookoian, S. C., Pirola, C. J., & Targher, G. (2015) · Metabolism · doi:10.1016/j.metabol.2015.09.017 · Cited by 236 · see citing works
Hepatic lipid droplets: A balancing act between energy storage and metabolic dysfunction in NAFLD
Mashek, D. G. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101115 · Cited by 233 · see citing works
Smagris, E., Gilyard, S., BasuRay, S., Cohen, J. C., & Hobbs, H. H. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.719955 · Cited by 226 · see citing works
Sookoian, S., & Pirola, C. J. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.14112 · Cited by 230 · see citing works
Fracanzani, A. L., Petta, S., Lombardi, R., Pisano, G., Russello, M., Consonni, D., Marco, V. D., Cammà, C., Mensi, L., Dongiovanni, P., et al. (2017) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2017.04.045 · Cited by 230 · see citing works
Self-citationSookoian, S. C., Castaño, G. O., Scian, R., Mallardi, P., Gianotti, T. F., Burgueño, A. L., Martino, J. S., & Pirola, C. J. (2014) · Hepatology · doi:10.1002/hep.27556 · Cited by 219 · see citing works
Genetic predisposition in nonalcoholic fatty liver disease
Sookoian, S. C., & Pirola, C. J. (2017) · Clinical and Molecular Hepatology · doi:10.3350/cmh.2016.0109 · Cited by 215 · see citing works
Role of Cholesterol‐Associated Steatohepatitis in the Development of NASH
Horn, C. L., Morales, A. L., Savard, C. E., Farrell, G. C., & Ioannou, G. N. (2021) · Hepatology Communications · doi:10.1002/hep4.1801 · Cited by 215 · see citing works
Tillman, E. J., & Rolph, T. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.601290 · Cited by 209 · see citing works
Leveraging Human Genetics to Identify Potential New Treatments for Fatty Liver Disease
Romeo, S., Sanyal, A. J., & Valenti, L. V. C. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.12.002 · Cited by 203 · see citing works
Self-citationYu, J., Marsh, S., Hu, J., Feng, W., & Wu, C. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/2862173 · Cited by 199 · 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
Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease
Mato, J. M., Alonso, C., Noureddin, M., & Lu, S. C.-L. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i24.3009 · Cited by 201 · see citing works
Nonalcoholic fatty liver disease: Evolving paradigms
Lonardo, A., Nascimbeni, F., Maurantonio, M., Marrazzo, A., Rinaldi, L., & Adinolfi, L. E. (2017) · World Journal of Gastroenterology · doi:10.3748/wjg.v23.i36.6571 · Cited by 197 · see citing works
Cardiovascular Risk in Non-Alcoholic Fatty Liver Disease: Mechanisms and Therapeutic Implications
Tana, C., Ballestri, S., Ricci, F., Vincenzo, A. D., Ticinesi, A., Gallina, S., Giamberardino, M. A., Cipollone, F., Sutton, R., Vettor, R., et al. (2019) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph16173104 · Cited by 191 · see citing works
Zheng, H., Sechi, L. A., Navarese, E. P., Casu, G., & Vidili, G. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02434-5 · Cited by 190 · see citing works
Pathogenesis of MASLD and MASH – role of insulin resistance and lipotoxicity
Bansal, S., & Bansal, M. B. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17930 · Cited by 187 · see citing works
Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease
Chao, H., Chao, S.-W., Lin, H., Ku, H., & Cheng, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020298 · Cited by 183 · see citing works
Pathophysiological mechanisms underlying MAFLD
Kuchay, M. S., Choudhary, N. S., & Mishra, S. K. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.09.026 · Cited by 180 · see citing works
Nonalcoholic Fatty Liver Disease Pandemic Fuels the Upsurge in Cardiovascular Diseases
Cai, J., Zhang, X., Ji, Y., Zhāng, P., She, Z., & Li, H. (2020) · Circulation Research · doi:10.1161/circresaha.119.316337 · Cited by 179 · see citing works
Carlsson, B., Lindén, D., Brolén, G., Liljeblad, M., Bjursell, M., Romeo, S., & Loomba, R. (2020) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.15738 · Cited by 169 · see citing works
Self-citationPirola, C. J., & Sookoian, S. C. (2015) · Hepatology · doi:10.1002/hep.28142 · Cited by 171 · see citing works
Nobili, V., Alisi, A., Newton, K. P., & Schwimmer, J. B. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.03.009 · Cited by 171 · see citing works
Self-citationNonalcoholic fatty liver disease: cause or consequence of type 2 diabetes?
Valenti, L., Bugianesi, E., Pajvani, U., & Targher, G. (2016) · Liver International · doi:10.1111/liv.13185 · Cited by 171 · see citing works
Self-citationPathophysiology of Non Alcoholic Fatty Liver Disease
Petta, S., Gastaldelli, A., Rebelos, E., Bugianesi, E., Messa, P., Miele, L., Svegliati‐Baroni, G., Valenti, L. V. C., & Bonino, F. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17122082 · Cited by 170 · see citing works
Self-citationNAFLD, and cardiovascular and cardiac diseases: Factors influencing risk, prediction and treatment
Targher, G., Corey, K. E., & Byrne, C. D. (2020) · Diabetes & Metabolism · doi:10.1016/j.diabet.2020.101215 · Cited by 170 · see citing works
Insights into the Epidemiology, Pathogenesis, and Therapeutics of Nonalcoholic Fatty Liver Diseases
Yu, Y., Cai, J., She, Z., & Li, H. (2018) · Advanced Science · doi:10.1002/advs.201801585 · Cited by 163 · see citing works
The Genetics of Nonalcoholic Fatty Liver Disease: Spotlight on PNPLA3 and TM6SF2
Day, C. P., & Anstee, Q. M. (2015) · Seminars in Liver Disease · doi:10.1055/s-0035-1562947 · Cited by 161 · see citing works
Boyle, M., Masson, S., & Anstee, Q. M. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.006 · Cited by 159 · see citing works
Found in translation—Fibrosis in metabolic dysfunction–associated steatohepatitis (MASH)
Wang, S., & Friedman, S. L. (2023) · Science Translational Medicine · doi:10.1126/scitranslmed.adi0759 · Cited by 158 · see citing works
Genetic and epigenetic factors determining NAFLD risk
Jonas, W., & Schürmann, A. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101111 · Cited by 157 · see citing works
Nonalcoholic Fatty Liver Disease in Children
Mann, J. P., Valenti, L. V. C., Scorletti, E., Byrne, C. D., & Nobili, V. (2018) · Seminars in Liver Disease · doi:10.1055/s-0038-1627456 · Cited by 161 · see citing works
Self-citationLiver fat accumulation is associated with circulating PCSK9
Ruscica, M., Ferri, N., Macchi, C., Meroni, M., Lanti, C., Ricci, C., Maggioni, M., Fracanzani, A. L., Badiali, S., Fargion, S. R., et al. (2016) · Annals of Medicine · doi:10.1080/07853890.2016.1188328 · Cited by 154 · see citing works
Self-citationNon-alcoholic fatty liver disease and cardiovascular disease: assessing the evidence for causality
Brouwers, M. C. G. J., Simons, N., Stehouwer, C. D. A., & Isaacs, A. J. (2019) · Diabetologia · doi:10.1007/s00125-019-05024-3 · Cited by 153 · see citing works
Genetic Factors in the Pathogenesis of Nonalcoholic Fatty Liver and Steatohepatitis
Dongiovanni, P., Romeo, S., & Valenti, L. V. C. (2015) · BioMed Research International · doi:10.1155/2015/460190 · Cited by 150 · see citing works
Self-citationTM6SF2: A Novel Genetic Player in Nonalcoholic Fatty Liver and Cardiovascular Disease
Luo, F., Oldoni, F., & Das, A. (2021) · Hepatology Communications · doi:10.1002/hep4.1822 · Cited by 147 · see citing works
Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD)
Campo, J. A. D., Gallego‐Durán, R., Gallego, P., & Grande, L. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19030911 · Cited by 146 · see citing works
Jamialahmadi, O., Vincentis, A. D., Tavaglione, F., Malvestiti, F., Li‐Gao, R., Mancina, R. M., Alvarez, M., Gelev, K. Z., Maurotti, S., Gentilucci, U. V., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03284-0 · Cited by 148 · see citing works
Self-citationStratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization
Björnson, E., Mukhopadhyay, B., Asplund, A., Pristovšek, N., Çınar, R., Romeo, S., Uhlén, M., Kunos, G., Nielsen, J., & Mardinoğlu, A. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.045 · Cited by 142 · see citing works
Self-citationFougerat, A., Montagner, A., Loiseau, N., Guillou, H., & Wahli, W. (2020) · Cells · doi:10.3390/cells9071638 · Cited by 143 · 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
Goffredo, M., Caprio, S., Feldstein, A. E., D’Adamo, E., Shaw, M. M., Pierpont, B. M., Savoye, M., Zhao, H., Bale, A. E., & Santoro, N. (2015) · Hepatology · doi:10.1002/hep.28283 · Cited by 139 · see citing works
Non-alcoholic fatty liver disease and risk of type 2 diabetes
Lallukka, S., & Yki‐Järvinen, H. (2016) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2016.06.006 · Cited by 138 · see citing works
Lipid metabolism in MASLD and MASH: From mechanism to the clinic
Carli, F., Della Pepa, G., Sabatini, S., Vidal Puig, A., & Gastaldelli, A. (2024) · JHEP Reports · doi:10.1016/j.jhepr.2024.101185 · Cited by 147 · see citing works
Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review
Ajmera, V. H., Terrault, N. A., & Harrison, S. A. (2017) · Hepatology · doi:10.1002/hep.29055 · Cited by 137 · see citing works
Cherubini, A., Ostadreza, M., Jamialahmadi, O., Pelusi, S., Rrapaj, E., Casirati, E., Passignani, G., Norouziesfahani, M., Sinopoli, E., Baselli, G., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02553-8 · Cited by 136 · see citing works
Self-citationGenetic Pathways in Nonalcoholic Fatty Liver Disease: Insights From Systems Biology
Sookoian, S. C., Pirola, C. J., Valenti, L. V. C., & Davidson, N. O. (2020) · Hepatology · doi:10.1002/hep.31229 · Cited by 129 · see citing works
Self-citationMERTK rs4374383 polymorphism affects the severity of fibrosis in non-alcoholic fatty liver disease
Petta, S., Valenti, L. V. C., Marra, F., Grimaudo, S., Tripodo, C., Bugianesi, E., Cammà, C., Cappon, A., Marco, V. D., Maira, G. D., et al. (2015) · Journal of Hepatology · doi:10.1016/j.jhep.2015.10.016 · Cited by 127 · see citing works
Self-citationLuukkonen, P. K., Zhou, Y., Haridas, P. A. N., Dwivedi, O. P., Hyötyläinen, T., Ali, A., Juuti, A., Leivonen, M., Tukiainen, T., Ahonen, L. L., et al. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.02.014 · Cited by 126 · see citing works
MASLD and the Development of HCC: Pathogenesis and Therapeutic Challenges
Phoolchund, A. G. S., & Khakoo, S. (2024) · Cancers · doi:10.3390/cancers16020259 · Cited by 127 · see citing works
Prill, S., Caddeo, A. M., Baselli, G., Jamialahmadi, O., Dongiovanni, P., Rametta, R., Kanebratt, K. P., Pujia, A., Pingitore, P., Mancina, R. M., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-47737-w · Cited by 123 · see citing works
Self-citationNutrition and Genetics in NAFLD: The Perfect Binomium
Meroni, M., Longo, M., Rustichelli, A., & Dongiovanni, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082986 · Cited by 122 · see citing works
Self-citationEslam, M., Mangia, A., Berg, T., Chan, H. L., Irving, W. L., Dore, G. J., Abate, M. L., Bugianesi, E., Adams, L. A., Najim, M. A., et al. (2016) · Hepatology · doi:10.1002/hep.28475 · Cited by 122 · see citing works
Genetics of nonalcoholic fatty liver disease
Dongiovanni, P., & Valenti, L. V. C. (2015) · Metabolism · doi:10.1016/j.metabol.2015.08.018 · Cited by 115 · see citing works
Self-citation
- Authors
- Dongiovanni, P., Petta, S., Maglio, C., Fracanzani, A. L., Pipitone, R., Mozzi, E., Motta, B. M., Kaminska, D., Rametta, R., Grimaudo, S., Pelusi, S., Montalcini, T., Alisi, A., Maggioni, M., Kärjä, V., Borén, J., Käkelä, P., Di Marco, V., Xing, C., Nobili, V., Dallapiccola, B., Craxi, A., Pihlajamäki, J., Fargion, S., Sjöström, L., Carlsson, L. M., Romeo, S., & Valenti, L.
- Affiliations
- University of Milan (IT)
- University of Palermo (IT)
- University of Gothenburg (SE)
- Department of Public Health and Clinical Nutrition, Surgery and Pathology,University of Eastern Finland,Kuopio,Finland
- Magna Graecia University (IT)
- Bambino Gesù Children's Hospital (IT)
- University of Eastern Finland (FI)
- Department of Gastroenterology,Università di Palermo,Palermo,Italy
- The University of Texas Southwestern Medical Center (US)
- Hepato‐Metabolic Unit and Scientific Direction,Ospedale Bambin Gesù,Roma,Italy
- Corresponding author
- Romeo, Stefano
- Valenti, Luca
- ORCID
- Dongiovanni, Paola
- Petta, Salvatore
- Maglio, Cristina
- Fracanzani, Anna Ludovica
- Pipitone, Rosaria
- Mozzi, Enrico
- Motta, Benedetta Maria
- Rametta, Raffaela
- Grimaudo, Stefania
- Pelusi, Serena
- Montalcini, Tiziana
- Alisi, Anna
- Maggioni, Marco
- Borén, Jan
- Käkelä, Pirjo
- Xing, Chao
- Dallapiccola, Bruno
- Pihlajamäki, Jussi
- Fargion, Silvia
- Carlsson, Lena M.
- Romeo, Stefano
- Valenti, Luca
- Venue
- Hepatology
- Published
- 2015-01-20
- Volume
- 61
- Issue
- 2
- Pages
- 506-514
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- OpenAlex
- W2030379010
- Cited by
- 533
- References
- 37
- Citations by year
- 2026: 15 · 2025: 27 · 2024: 37 · 2023: 45 · 2022: 42 · 2021: 66 · 2020: 73 · 2019: 47 · 2018: 30 · 2017: 44 · 2016: 46 · 2015: 53 · 2014: 5 · 2012: 1
- FWCI
- 37.37
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion, other-oa)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- Academy of Finland
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano
- Kuopio University Hospital
- Novonordisk Foundation
- Università degli studi di milano
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- TM6SF2, nonalcoholic steatohepatitis, cardiovascular disease, carotid atherosclerosis, very low density lipoprotein secretion, hepatic steatosis, liver fibrosis, PNPLA3 I148M, serum lipids, myocardial infarction, genetic risk variants, liver biopsy
- MeSH terms
- Adult, Biopsy, Carotid Artery Diseases, Cross-Sectional Studies, Female, Humans, Lipoproteins, VLDL, Liver, Liver Cirrhosis, Male, Membrane Proteins, Middle Aged, Obesity, Cohort Studies, Hepatocytes, 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
