Abstract
Background
Given the importance of fibrosis in the progression of non-alcoholic fatty liver disease (NAFLD), identifying biochemical and histopathological aspects associated with its severity is important to determine the course of disease in high-risk populations.
Objectives
The study aims to investigate correlations between biochemical and histopathological variables associated with the occurrence and severity of NAFLD-related liver fibrosis in individuals with obesity.
Methods
This is a cross-sectional study which enrolled 171 individuals who underwent bariatric surgery at a tertiary university hospital. Clinical, laboratory, and histopathological hepatic characteristics were analyzed. Univariate and multivariate analyses were carried out to identify factors associated with the outcomes studied (severity of fibrosis staging) through simple and multiple regression models.
Results
Female were 87.7%, and the mean age was 38.4 ± 9.3 years. The most common histopathological abnormalities were macrovesicular steatosis (74.9%) and hepatocellular ballooning (40.4%). In the histopathological univariate analysis, liver fibrosis significantly correlated with severities of microvesicular steatosis (p = 0.003), lobular inflammation (p = 0.001), and NAS (p < 0.001). In the multivariate analysis, the degrees of microvesicular steatosis (p < 0.001) and NAS (p < 0.001) independently correlated with fibrosis severity. In the univariate biochemical analysis, fibrosis severity significantly correlated with levels of hemoglobin A1c (p = 0.004) and glucose (p = 0.01). In the multivariate analysis, glucose levels independently correlated with liver fibrosis degree (p = 0.007).
Conclusion
Significant and independent associations were observed between the intensities of microvesicular steatosis, NAS, and glucose levels and the severity degree of liver fibrosis in individuals with obesity.
Graphical Abstract
Similar content being viewed by others
References
Sheka AC, Adeyi O, Thompson J, et al. Nonalcoholic steatohepatitis: a review. JAMA. 2020;323(12):1175–83.
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015;313(22):2263–73.
Cheung A, Figueredo C, Rinella ME. Nonalcoholic fatty liver disease: identification and management of high-risk patients. Am J Gastroenterol. 2019;114(4):579–90.
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.
Brunt EM, Kleiner DE, Carpenter DH, et al. American association for the study of liver diseases NASH task force. NAFLD: reporting histologic findings in clinical practice. Hepatology. 2021;73(5):2028–38.
Lazarus JV, Mark HE, Allen AM, et al. Healthy Livers, healthy lives collaborators. A global research priority agenda to advance public health responses to fatty liver disease. J Hepatol. 2023;79(3):618–34.
Lekakis V, Papatheodoridis GV. Natural history of metabolic dysfunction-associated steatotic liver disease. Eur J Intern Med. 2023;S0953–6205(23):00397–407.
de Souza EL, Mounzer DLS, Gestic MA, et al. Fibrotic NASH in individuals with obesity: a cross-sectional analysis of the prevalence of this significant milestone of disease progression and accuracy of a non-invasive marker for its screening. Obes Surg. 2023. https://doi.org/10.1007/s11695-023-06998-1.
Talha M, Ali MH. Obesity, type 2 diabetes, NASH, and the promising role of bariatric surgery: insights from the BRAVES trial. Obes Surg. 2023;33(12):4181–2.
Jimenez LS, Mendonça Chaim FH, Mendonça Chaim FD, et al. Impact of weight regain on the evolution of non-alcoholic fatty liver disease after Roux-en-Y gastric bypass: a 3-year follow-up. Obes Surg. 2018;28(10):3131–5.
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.
Brunt EM, Janney CG, Di Bisceglie AM, et al. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol. 1999;94(9):2467–74.
Kleiner DE, Brunt EM, Van Natta M, et al. Nonalcoholic steatohepatitis clinical research network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.
Ekstedt M, Hagström H, Nasr P, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547–54.
Hagström H, Nasr P, Ekstedt M, et al. Fibrosis stage but not NASH predicts mortality and time to development of severe liver disease in biopsy-proven NAFLD. J Hepatol. 2017;67(6):1265–73.
Germano CW, Mega PF, Mattosinho TJAP, et al. Microvesicular steatosis in individuals with obesity: a histological marker of non-alcoholic fatty liver disease severity. Obes Surg. 2023;33(3):813–20.
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.
Tandra S, Yeh MM, Brunt EM, et al. Presence and significance of microvesicular steatosis in nonalcoholic fatty liver disease. J Hepatol. 2011;55(3):654–9.
Tamaki N, Munaganuru N, Jung J, et al. Clinical utility of change in nonalcoholic fatty liver disease activity score and change in fibrosis in NAFLD. Clin Gastroenterol Hepatol. 2021;19(12):2673–4.
Kleiner DE, Brunt EM, Wilson LA, et al. Nonalcoholic steatohepatitis clinical research network. Association of histologic disease activity with progression of nonalcoholic fatty liver disease. JAMA Netw Open. 2019;2(10):e1912565.
Haukeland JW, Konopski Z, Linnestad P, et al. Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease. Scand J Gastroenterol. 2005;40(12):1469–77.
Ayres ABS, Carneiro CRG, Gestic MA, et al. Identification of predictors of non-alcoholic steatohepatitis and its severity in individuals undergoing bariatric surgery. Obes Surg. 2024;34(2):456–66.
Siddiqui MT, Amin H, Garg R. Medications in type-2 diabetics and their association with liver fibrosis. World J Gastroenterol. 2020;26(23):3249–59.
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.
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.
Cazzo E, Gestic MA, Utrini MP, et al. 2017 Bariatric surgery in individuals with liver cirrhosis: a narrative review. Rev Assoc Med Bras. 1992;63(2):190–4.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Human and Animal Rights
The study was approved by the local committee of ethics in research under the reference number 5.921.274/FCM-UNICAMP and all participants signed an informed consent form. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict of Interest
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Key Points
1. The intensity of microvesicular steatosis independently correlated with liver fibrosis severity.
2. Non-alcoholic fatty liver disease Activity Score (NAS) independently correlated with liver fibrosis severity.
3. Glucose levels independently correlated with liver fibrosis severity.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Carneiro, C.R.G., Ayres, A.B.S., Gestic, M.A. et al. Association of Histopathological and Biochemical Aspects of NAFLD With the Severity of Liver Fibrosis in Individuals With Obesity: Cross-sectional Study. OBES SURG 34, 1569–1574 (2024). https://doi.org/10.1007/s11695-024-07180-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11695-024-07180-x