Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison
Keywords:
Non-alcoholic fatty liver disease, Obesity, Bariatric surgery, Weight loss, Insulin resistance, Liver steatosis, Non-alcoholic steatohepatitis, Liver fibrosis, Hepatocellular ballooning, Hepatic lobular inflammation, Hepatic portal inflammationAbstract
BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL.
OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL.
DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil.
METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected.
RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group.
CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and microvesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.
Downloads
References
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328-
PMID: 28714183; https://doi.org/10.1002/hep.29367.
Brunt EM, Kleiner DE, Carpenter DH, et al. NAFLD: Reporting histologic findings in clinical practice. Hepatology. 2021;73(5):2028-38. PMID: 33111374; https://doi.org/10.1002/hep.31599.
Cazzo E, Pareja JC, Chaim EA. Nonalcoholic fatty liver disease and bariatric surgery: a comprehensive review. Sao Paulo Med J. 2017;135(3):277-95. PMID: 28562737; https://doi.org/10.1590/15163180.2016.0306311216.
Bhala N, Younes R, Bugianesi E. Epidemiology and natural history of patients with NAFLD. Curr Pharm Des. 2013;19(29):5169-76. PMID: 23394091; https://doi.org/10.2174/13816128113199990336.
Duseja A, Chalasani N. Epidemiology and risk factors of nonalcoholic fatty liver disease (NAFLD). Hepatol Int. 2013;7(s2):755-64. PMID: 26202291; https://doi.org/10.1007/s12072-013-9480-x.
Fakhry TK, Mhaskar R, Schwitalla T, et al. Bariatric surgery improves nonalcoholic fatty liver disease: a contemporary systematic review and meta-analysis. Surg Obes Relat Dis. 2019;15(3):502-11. PMID: 30683512; https://doi.org/10.1016/j.soard.2018.12.002.
Kashyap SR, Diab DL, Baker AR, et al. Triglyceride levels and not adipokine concentrations are closely related to severity of nonalcoholic fatty liver disease in an obesity surgery cohort. Obesity (Silver Spring). 2009;17(9):1696-701. PMID: 19360015; http://doi.org/10.1038/ oby.2009.89.
Guajardo-Salinas GE, Hilmy A. Prevalence of nonalcoholic fatty liver disease (NAFLD) and utility of FIBROspect II to detect liver fibrosis in morbidly obese Hispano-American patients undergoing gastric bypass. Obes Surg. 2010;20(12):1647-53. PMID: 19957049; https://doi. org/10.1007/s11695-009-0027-0.
Cazzo E, de Felice Gallo F, Pareja JC, Chaim EA. Nonalcoholic fatty liver disease in morbidly obese subjects: correlation among histopathologic findings, biochemical features, and ultrasound evaluation. Obes Surg. 2014;24(4):666-8. PMID: 24415281; https:// doi.org/10.1007/s11695-014-1183-4.
Agarwal L, Aggarwal S, Shalimar, et al. Bariatric surgery in nonalcoholic fatty liver disease (NAFLD): Impact Assessment Using Paired Liver Biopsy and Fibroscan. Obes Surg. 2021;31(2):617-26. PMID: 33052552; https:// doi.org/10.1007/s11695-020-04977-4.
Pedersen JS, Rygg MO, Serizawa RR, et al. Effects of Roux-en-Y gastric bypass and sleeve gastrectomy on non-alcoholic fatty liver disease: a 12-month follow-up study with paired liver biopsies. J Clin Med. 2021;10(17):3783. PMID: 34501231; https://doi.org/10.3390/ jcm10173783.
de Jesus RN, Callejas GH, David Mendonça Chaim F, et al. Roux-en-Y gastric bypass as a treatment for hepatic iron overload: an exploratory study. Obes Surg. 2022;32(7):2438-44. PMID: 35543890; https://doi. org/10.1007/s11695-022-06103-y.
Murakami E, Nakahara T, Hiramatsu A, et al. Therapeutic effects of sleeve gastrectomy for non-alcoholic steatohepatitis estimated by paired liver biopsy in morbidly obese Japanese patients. Medicine (Baltimore). 2021;100(26):e26436. PMID: 34190166; https://doi.org/10.1097/ md.0000000000026436.
Chaim EA, Pareja JC, Gestic MA, Utrini MP, Cazzo E. Preoperative multidisciplinary program for bariatric surgery: a proposal for the Brazilian Public Health System. Arq Gastroenterol. 2017;54(1):70-4. PMID: 28079244; https://doi.org/10.1590/s0004-2803.2017v54n1-14.
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-9. PMID: 3899825; https://doi.org/10.1007/bf00280883.
Han L, Zhang T, You D, et al. Temporal and mediation relations of weight loss, and changes in insulin resistance and blood pressure in response to 2-year weight-loss diet interventions: the POUNDS Lost trial. Eur J Nutr. 2022;61(1):269-75. PMID: 34319427; https://doi.org/10.1007/ s00394-021-02643-8.
Herrington GJ, Peterson JJ, Cheng L, et al. The use of very low-calorie diets in subjects with obesity complicated with nonalcoholic fatty liver disease: a scoping review. Obes Sci Pract. 2022;8(4):510-24. PMID: 35949283; https://doi.org/10.1002/osp4.589.
D’Alonzo NJ, Qiu L, Sears DD, et al. WISER Survivor Trial: Combined effect of exercise and weight loss interventions on insulin and insulin resistance in breast cancer survivors. Nutrients. 2021;13(9):3108. PMID: 34578984; https://doi.org/10.3390/nu13093108.
Concon MM, Jimenez LS, Callejas GH, Chaim EA, Cazzo E. Influence of post-Roux-en-Y gastric bypass weight recidivism on insulin resistance: a 3-year follow-up. Surg Obes Relat Dis. 2019;15(11):1912-6. PMID: 31631000; http://doi.org/10.1016/j.soard.2019.08.023.
Cazzo E, Gestic MA, Utrini MP, et al. influence of insulin resistance status on the development of gallstones following Roux-En-Y gastric bypass: a prospective cohort study. Obes Surg. 2016;26(4):769-75. PMID: 26210194; http://doi.org/10.1007/s11695-015-1815-3.
Gluchowski NL, Becuwe M, Walther TC, Farese RV Jr. Lipid droplets and liver disease: from basic biology to clinical implications. Nat Rev Gastroenterol Hepatol. 2017;14(6):343-55. PMID: 28428634; https://doi. org/10.1038/nrgastro.2017.32.
Rambold AS, Cohen S, Lippincott-Schwartz J. Fatty acid trafficking in starved cells: regulation by lipid droplet lipolysis, autophagy, and mitochondrial fusion dynamics. Dev Cell. 2015;32(6):678-92. PMID: 25752962; https://doi.org/10.1016/j.devcel.2015.01.029.
Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis.
Hepatology. 2010;51(1):121-9. PMID: 19827166; https://doi. org/10.1002/hep.23276.
Celebi G, Cicek AF, Gurel H, et al. Microvesicular steatosis: a missed item in the management of nonalcoholic fatty liver disease? Acta Gastroenterol Belg. 2020;83(4):565-70. PMID: 33321012.
Tandra S, Yeh MM, Brunt EM, et al. Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease. J Hepatol.
;55(3):654-9. PMID: 21172393; https://doi.org/10.1016/j. jhep.2010.11.021.
Hwang S, Lee SG, Jang SJ, et al. The effect of donor weight reduction on hepatic steatosis for living donor liver transplantation. Liver Transpl. 2004;10(6):721-5. PMID: 15162464; https://doi.org/10.1002/ lt.20172.
Brunt EM, Kleiner DE, Wilson LA, et al. Portal chronic inflammation in nonalcoholic fatty liver disease (NAFLD): a histologic marker of advanced NAFLD-Clinicopathologic correlations from the nonalcoholic steatohepatitis clinical research network. Hepatology. 2009;49(3):809-
PMID: 19142989; https://doi.org/10.1002/hep.22724.
Vilar-Gomez E, Martinez-Perez Y, Calzadilla-Bertot L, et al. Weight loss through lifestyle modification significantly reduces features of nonalcoholic steatohepatitis. Gastroenterology. 2015;149(2):36778.e5; quiz e14-5. PMID: 25865049; https://doi.org/10.1053/j. gastro.2015.04.005.
Salman AA, Sultan AAEA, Abdallah A, et al. Effect of weight loss induced by laparoscopic sleeve gastrectomy on liver histology and serum adipokine levels. J Gastroenterol Hepatol. 2020;35(10):1769-73. PMID: 32153044; https://doi.org/10.1111/jgh.15029.
Praveen Raj P, Gomes RM, Kumar S, et al. The effect of surgically induced weight loss on nonalcoholic fatty liver disease in morbidly obese Indians: “NASHOST” prospective observational trial. Surg Obes Relat Dis. 2015;11(6):1315-22. PMID: 26003897; https://doi.org/10.1016/j. soard.2015.02.006.
Kreve F, Callejas GH, Jimenez LS, et al. Trajectory of NAFLD characteristics after Roux-en-Y gastric bypass: a five-year historical cohort study.
Sao Paulo Med J. 2022;140(6):739-46. PMID: 36102453; https://doi. org/10.1590/1516-3180.2021.0828.07012022.
Aly S, Hachey K, Pernar LIM. Gender disparities in weight loss surgery. Mini-invasive Surg. 2020;4:21. https://doi.org/10.20517/25741225.2019.57.
Bal J, Ilonzo N, Adediji T, Leitman IM. Gender as a Deterministic Factor in Procedure Selection and Outcomes in Bariatric Surgery. JSLS. 2021;25(1):e2020.00077. PMID: 33628005; https://doi.org/10.4293/ JSLS.2020.00077.
Kennedy-Dalby A, Adam S, Ammori BJ, Syed AA. Weight loss and metabolic outcomes of bariatric surgery in men versus women - A matched comparative observational cohort study. Eur J Intern Med. 2014;25(10):922-5. PMID: 25468739; https://doi.org/10.1016/j. ejim.2014.10.020.
Lonardo A, Nascimbeni F, Ballestri S, et al. Sex differences in nonalcoholic fatty liver disease: state of the art and identification of research gaps. Hepatology. 2019;70(4):1457-69. PMID: 30924946; https://doi. org/10.1002/hep.30626.
Concon MM, Gestic MA, Utrini MP, et al. Should routine liver biopsy be considered in bariatric surgical practice? An analysis of the limitations of non-invasive NAFLD markers. Arq Gastroenterol. 2022;59(1):110-6. PMID: 35442320; https://doi.org/10.1590/S0004-2803.202200001-19.
Jimenez LS, Marques RA, Gestic MA, et al. Non-invasive markers in non-alcoholic fatty liver disease: reliability is variable according to BMI status. Obes Surg. 2021;31(8):3888-92. PMID: 33913073; https:// doi.org/10.1007/s11695-021-05429-3.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 São Paulo Medical Journal
This work is licensed under a Creative Commons Attribution 4.0 International License.
