Modifications of IGF2 and EGFR plasma protein concentrations in NAFLD patients after bariatric surgery.
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
21
05
2020
accepted:
09
09
2020
revised:
20
08
2020
pubmed:
19
9
2020
medline:
21
1
2022
entrez:
18
9
2020
Statut:
ppublish
Résumé
Nonalcoholic fatty liver disease (NAFLD) is strictly associated with the epidemic of obesity and is becoming the most prevalent liver disease worldwide. In severe obesity, bariatric surgery (BS) is the most effective treatment not only for obesity but also for the associated metabolic co-morbidities, NAFLD, among others. To date, noninvasive diagnostic/prognostic methods cannot evaluate hepatic improvements following surgery. We aimed to measure plasma level of insulin-growth factor-2 protein (IGF2) and epithermal growth factor receptor (EGFR), and to assess their relationship with clinical and biochemical parameters during the 12 months follow-up. Demographic, clinical-biochemical data, and plasma IGF2 and EGFR were measured in 69 patients preoperatively (T0) and 6 and 12 months (T6M and T12M, respectively) after BS. Liver biopsy was performed at T0. Relationships between IGF2, EGFR, and several biochemical parameters were performed using Pearson or Spearman correlation analysis. IGF2 plasma level increases during follow-up, passing from 2.5 (1.8-15.5) at baseline to 13.3 (8.6-19.1) at T12M, p < 0.001. Conversely, EGFR showed a not significant reduction. At T12M, the plasma level of both markers was comparable to those of lean subjects. The clinical-biochemical parameters (BMI, glycated hemoglobin, HOMA-IR) also return to the normal range at T12M. Correlation analysis demonstrated that IGF2 was significantly associated with total bilirubin, direct bilirubin, and albumin at T0 while with blood glucose, ALT, GGT, and AST/ALT ratio at T6M and T12M. IGF2 plasma levels increase after bariatric surgery, and these changes are associated with the modification of hepatic biochemical parameters, even if other clinic or metabolic improvements cannot be excluded.
Sections du résumé
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is strictly associated with the epidemic of obesity and is becoming the most prevalent liver disease worldwide. In severe obesity, bariatric surgery (BS) is the most effective treatment not only for obesity but also for the associated metabolic co-morbidities, NAFLD, among others. To date, noninvasive diagnostic/prognostic methods cannot evaluate hepatic improvements following surgery.
OBJECTIVES
We aimed to measure plasma level of insulin-growth factor-2 protein (IGF2) and epithermal growth factor receptor (EGFR), and to assess their relationship with clinical and biochemical parameters during the 12 months follow-up.
METHODS
Demographic, clinical-biochemical data, and plasma IGF2 and EGFR were measured in 69 patients preoperatively (T0) and 6 and 12 months (T6M and T12M, respectively) after BS. Liver biopsy was performed at T0. Relationships between IGF2, EGFR, and several biochemical parameters were performed using Pearson or Spearman correlation analysis.
RESULTS
IGF2 plasma level increases during follow-up, passing from 2.5 (1.8-15.5) at baseline to 13.3 (8.6-19.1) at T12M, p < 0.001. Conversely, EGFR showed a not significant reduction. At T12M, the plasma level of both markers was comparable to those of lean subjects. The clinical-biochemical parameters (BMI, glycated hemoglobin, HOMA-IR) also return to the normal range at T12M. Correlation analysis demonstrated that IGF2 was significantly associated with total bilirubin, direct bilirubin, and albumin at T0 while with blood glucose, ALT, GGT, and AST/ALT ratio at T6M and T12M.
CONCLUSIONS
IGF2 plasma levels increase after bariatric surgery, and these changes are associated with the modification of hepatic biochemical parameters, even if other clinic or metabolic improvements cannot be excluded.
Identifiants
pubmed: 32943763
doi: 10.1038/s41366-020-00687-0
pii: 10.1038/s41366-020-00687-0
doi:
Substances chimiques
IGF2 protein, human
0
Insulin-Like Growth Factor II
67763-97-7
EGFR protein, human
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
374-382Références
Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, et al. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nat Rev Gastroenterol Hepatol. 2017. https://doi.org/10.1038/nrgastro.2017.109 .
Araújo AR, Rosso N, Bedogni G, Tiribelli C, Bellentani S. Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: what we need in the future. Liver Int. 2018;38:47–51.
pubmed: 29427488
Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118:1388–93.
pubmed: 17015527
Anderson EL, Howe LD, Jones HE, Higgins JPT, Lawlor DA, Fraser A. The prevalence of non-alcoholic fatty liver disease in children and adolescents: a systematic review and meta-analysis. PLoS ONE. 2015;10:e0140908.
pubmed: 26512983
pmcid: 4626023
McPherson S, Hardy T, Henderson E, Burt AD, Day CP, Anstee QM. Evidence of NAFLD progression from steatosis to fibrosing-steatohepatitis using paired biopsies: implications for prognosis and clinical management. J Hepatol. 2015;62:1148–55.
pubmed: 25477264
Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13:643–54.e1–9.
pubmed: 24768810
Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease. Gastroenterology. 2015;149:389–97.e10.
pubmed: 25935633
pmcid: 4516664
Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, et al. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology. 2018;68:349–60.
pubmed: 29222917
pmcid: 6511364
Drescher HK, Weiskirchen S, Weiskirchen R. Current status in testing for nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Cells. 2019;8. https://doi.org/10.3390/cells8080845 .
Dixon JB, Bhathal PS, O’Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001;121:91–100.
pubmed: 11438497
Gupta R, Bhangoo A, Matthews NAV, Anhalt H, Matta Y, Lamichhane B, et al. The prevalence of non-alcoholic fatty liver disease and metabolic syndrome in obese children. J Pediatr Endocrinol Metab. 2011;24:907–11.
pubmed: 22308841
WHO. Facts and figures on childhood obesity. WHO. http://www.who.int/end-childhood-obesity/facts/en/ . Accessed 1 Jul 2020.
MLRP Lima, SCO Mourão, MTC Diniz, VHR Leite. Hepatic histopathology of patients with morbid obesity submitted to gastric bypass. Obes Surg. 2005;15:661–9.
Bower G, Toma T, Harling L, Jiao LR, Efthimiou E, Darzi A, et al. Bariatric surgery and non-alcoholic fatty liver disease: a systematic review of liver biochemistry and histology. Obes Surg. 2015;25:2280–9.
pubmed: 25917981
Billeter AT, de la Garza Herrera JR, Scheurlen KM, Nickel F, Billmann F, Müller-Stich BP. Management of endocrine disease: which metabolic procedure? Comparing outcomes in sleeve gastrectomy and Roux-en Y gastric bypass. Eur J Endocrinol. 2018;179:R77–93.
pubmed: 29764908
Caiazzo R, Lassailly G, Leteurtre E, Baud G, Verkindt H, Raverdy V, et al. Roux-en-Y gastric bypass versus adjustable gastric banding to reduce nonalcoholic fatty liver disease: a 5-year controlled longitudinal study. Ann Surg. 2014;260:893–8.
pubmed: 25379859
Kalinowski P, Paluszkiewicz R, Ziarkiewicz-Wróblewska B, Wróblewski T, Remiszewski P, Grodzicki M, et al. Liver function in patients with nonalcoholic fatty liver disease randomized to Roux-en-Y gastric bypass versus sleeve gastrectomy: a secondary analysis of a randomized clinical trial. Ann Surg. 2017;266:738–45.
pubmed: 28767558
Esquivel CM, Garcia M, Armando L, Ortiz G, Lascano FM, Foscarini JM. Laparoscopic sleeve gastrectomy resolves NAFLD: another formal indication for bariatric surgery? Obes Surg. 2018;28:4022–33.
pubmed: 30121855
Adamek A, Kasprzak A. Insulin-like growth factor (IGF) system in liver diseases. Int J Mol Sci. 2018;19. https://doi.org/10.3390/ijms19051308 .
Kessler SM, Laggai S, Van Wonterg E, Gemperlein K, Müller R, Haybaeck J, et al. Transient hepatic overexpression of insulin-like growth factor 2 induces free cholesterol and lipid droplet formation. Front Physiol. 2016;7:147.
pubmed: 27199763
pmcid: 4843762
Komposch K, Sibilia M. EGFR signaling in liver diseases. Int J Mol Sci. 2016;17. https://doi.org/10.3390/ijms17010030 .
Bhushan B, Michalopoulos GK. Role of epidermal growth factor receptor in liver injury and lipid metabolism: Emerging new roles for an old receptor. Chem Biol Interact. 2020;324:109090.
pubmed: 32283070
Divella R, Daniele A, Gadaleta C, Tufaro A, Venneri MT, Paradiso A, et al. Circulating transforming growth factor-β and epidermal growth factor receptor as related to virus infection in liver carcinogenesis. Anticancer Res. 2012;32:141–5.
pubmed: 22213299
Giraudi PJ, Gambaro SE, Ornelas Arroyo S, Chackelevicius CM, Giuricin M, Silvestri M, et al. A simple in silico strategy identifies candidate biomarkers for the diagnosis of liver fibrosis in morbidly obese subjects. Liver Int. 2018;38:155–63.
pubmed: 28650518
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.
pubmed: 3899825
Authors/Task Force Members, Rydén L, Grant PJ, Anker SD, Berne C, Cosentino F, et al. ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013;34:3035–87.
Palmisano S, Giacomel G, Silvestri M, Giuricin M, Kulla A, Giudici F, et al. Outcome of laparoscopic gastric bypass in obese and diabetic patients: when surgery fails. Minerva Chir. 2017;72:279–88.
pubmed: 28465502
Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41:1313–21.
pubmed: 15915461
pmcid: 15915461
Kleiner DE, Brunt EM. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32:3–13.
pubmed: 22418883
pmcid: 22418883
Cianfarani S, Inzaghi E, Alisi A, Germani D, Puglianiello A, Nobili V. Insulin-like growth factor-I and -II levels are associated with the progression of nonalcoholic fatty liver disease in obese children. J Pediatr. 2014;165:92–8.
pubmed: 24607243
Ajmera V, Perito ER, Bass NM, Terrault NA, Yates KP, Gill R, et al. Novel plasma biomarkers associated with liver disease severity in adults with nonalcoholic fatty liver disease. Hepatology. 2017;65:65–77.
pubmed: 27532276
GBD 2015 Obesity Collaborators, Afshin A, Forouzanfar MH, Reitsma MB, Sur P, Estep K, et al. Health effects of overweight and obesity in 195 countries over 25 years. N Engl J Med. 2017;377:13–27.
Angulo P. Nonalcoholic fatty liver disease. N Engl J Med. 2002;346:1221–31.
Kelly T, Yang W, Chen C-S, Reynolds K, He J. Global burden of obesity in 2005 and projections to 2030. Int J Obes. 2008;32:1431–7.
Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67:123–33.
Wong RJ, Aguilar M, Cheung R, Perumpail RB, Harrison SA, Younossi ZM, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. Gastroenterology. 2015;148:547–55.
pubmed: 25461851
Aguilar-Olivos NE, Almeda-Valdes P, Aguilar-Salinas CA, Uribe M, Méndez-Sánchez N. The role of bariatric surgery in the management of nonalcoholic fatty liver disease and metabolic syndrome. Metab Clin Exp. 2016;65:1196–207.
pubmed: 26435078
RNAMA Rehem, WMHM El-Shikh. Serum IGF-1, IGF-2 and IGFBP-3 as parameters in the assessment of liver dysfunction in patients with hepatic cirrhosis and in the diagnosis of hepatocellular carcinoma. Hepatogastroenterology. 2011;58:949–54.
Liu J, Hu X, Chen J, Li X, Wang L, Wang B, et al. Pericentral hepatocytes produce insulin-like growth factor-2 to promote liver regeneration during selected injuries in mice. Hepatology. 2017;66:2002–15.
pubmed: 28653763
Ichikawa T, Nakao K, Hamasaki K, Furukawa R, Tsuruta S, Ueda Y, et al. Role of growth hormone, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 in development of non-alcoholic fatty liver disease. Hepatol Int. 2007;1:287–94.
pubmed: 19669352
pmcid: 2716823
Sumida Y, Yonei Y, Tanaka S, Mori K, Kanemasa K, Imai S, et al. Lower levels of insulin-like growth factor-1 standard deviation score are associated with histological severity of non-alcoholic fatty liver disease. Hepatol Res. 2015;45:771–81.
pubmed: 25163357
Dichtel LE, Corey KE, Misdraji J, Bredella MA, Schorr M, Osganian SA, et al. The association between IGF-1 levels and the histologic severity of nonalcoholic fatty liver disease. Clin Transl Gastroenterol. 2017;8:e217.
pubmed: 28125073
pmcid: 5288606
Hagström H, Stål P, Hultcrantz R, Brismar K, Ansurudeen I. IGFBP-1 and IGF-I as markers for advanced fibrosis in NAFLD—a pilot study. Scand J Gastroenterol. 2017;52:1427–34.
pubmed: 28927302
Petäjä EM, Zhou Y, Havana M, Hakkarainen A, Lundbom N, Ihalainen J, et al. Phosphorylated IGFBP-1 as a non-invasive predictor of liver fat in NAFLD. Sci Rep. 2016;6:24740.
pubmed: 27091074
pmcid: 4835723
Chishima S, Kogiso T, Matsushita N, Hashimoto E, Tokushige K. The relationship between the growth hormone/insulin-like growth factor system and the histological features of nonalcoholic fatty liver disease. Intern Med. 2017;56:473–80.
pubmed: 28250290
pmcid: 5399195
Brynskov T, Laugesen CS, Floyd AK, Frystyk J, Sørensen TL. The IGF-axis and diabetic retinopathy before and after gastric bypass surgery. Obes Surg. 2017;27:408–15.
pubmed: 27465937
Street ME, Smerieri A, Montanini L, Predieri B, Iughetti L, Valenzise M, et al. Interactions among pro-inflammatory cytokines, IGF system and thyroid function in pre-pubertal obese subjects. J Biol Regul Homeost Agents. 2013;27:259–66.
pubmed: 23489706
Heald AH, Kärvestedt L, Anderson SG, McLaughlin J, Knowles A, Wong L, et al. Low insulin-like growth factor-II levels predict weight gain in normal weight subjects with type 2 diabetes. Am J Med. 2006;119:167.e9–15.
pubmed: 16443426
Sandhu MS, Gibson JM, Heald AH, Dunger DB, Wareham NJ. Low circulating IGF-II concentrations predict weight gain and obesity in humans. Diabetes. 2003;52:1403–8.
pubmed: 12765950
Chaim FDM, Pascoal LB, Chaim FHM, Palma BB, Damázio TA, da Costa LBE, et al. Histological grading evaluation of non-alcoholic fatty liver disease after bariatric surgery: a retrospective and longitudinal observational cohort study. Sci Rep. 2020;10:8496.
pubmed: 32444690
pmcid: 7244764
Baldwin D, Chennakesavalu M, Gangemi A. Systematic review and meta-analysis of Roux-en-Y gastric bypass against laparoscopic sleeve gastrectomy for amelioration of NAFLD using four criteria. Surg Obes Relat Dis. 2019;15:2123–30.
pubmed: 31711944
Sinclair P, Brennan DJ, le Roux CW. Gut adaptation after metabolic surgery and its influences on the brain, liver and cancer. Nat Rev Gastroenterol Hepatol. 2018;15:606–24.
pubmed: 30181611
Seeley RJ, Chambers AP, Sandoval DA. The role of gut adaptation in the potent effects of multiple bariatric surgeries on obesity and diabetes. Cell Metab. 2015;21:369–78.
pubmed: 25662404
pmcid: 4351155
Taqi E, Wallace LE, de Heuvel E, Chelikani PK, Zheng H, Berthoud H-R, et al. The influence of nutrients, biliary-pancreatic secretions, and systemic trophic hormones on intestinal adaptation in a Roux-en-Y bypass model. J Pediatr Surg. 2010;45:987–95.
pubmed: 20438940
Ceccarini G, Pelosini C, Ferrari F, Magno S, Vitti J, Salvetti G, et al. Serum IGF-binding protein 2 (IGFBP-2) concentrations change early after gastric bypass bariatric surgery revealing a possible marker of leptin sensitivity in obese subjects. Endocrine. 2019;65:86–93.
pubmed: 30945111
Yan J, Charles JF. Gut microbiota and IGF-1. Calcif Tissue Int. 2018;102:406–14.
pubmed: 29362822
pmcid: 6132071