Association between serum ferritin levels and histopathological severity of non-alcoholic fatty liver disease: a cross-sectional observational study
DOI:
https://doi.org/10.51168/421r5913Keywords:
advanced fibrosis, liver biopsy, NAFLD Activity Score, non-alcoholic steatohepatitis, serum ferritinAbstract
Background
Non-alcoholic fatty liver disease encompasses a spectrum from simple steatosis to steatohepatitis, progressive fibrosis, and cirrhosis. Serum ferritin is frequently elevated in affected patients, but its relationship with histological severity remains uncertain.
Objectives
To determine the association between serum ferritin concentration and histopathological severity among adults with biopsy-evaluated non-alcoholic fatty liver disease
Methods
This cross-sectional observational study included 100 adults at Government Medical College and Hospital, Vikarabad, Telangana, India, from September 2024 to August 2025. Demographic, metabolic, biochemical, serum ferritin, and liver histopathology data were analysed. Steatosis, lobular inflammation, hepatocyte ballooning, NAFLD Activity Score, and fibrosis stage were recorded. Correlation, logistic regression, and receiver operating characteristic analyses were performed.
Results
The mean age was 47.8 ± 11.2 years; 62.0% were male. Median serum ferritin was 286 ng/mL, and 46.0% had hyperferritinaemia. Definite steatohepatitis, significant fibrosis, and advanced fibrosis were present in 48.0%, 38.0%, and 17.0%, respectively. Ferritin increased across steatosis grades and fibrosis categories. Levels were higher in definite steatohepatitis than in its absence (421 versus 204 ng/mL). Ferritin correlated with NAFLD Activity Score (ρ=0.58) and fibrosis stage (ρ=0.49). Each 100-ng/mL increase independently raised the adjusted odds of steatohepatitis and advanced fibrosis. Areas under the curve were 0.79 for steatohepatitis and 0.82 for advanced fibrosis.
Conclusion
Higher serum ferritin was independently associated with greater necroinflammatory activity and fibrosis severity in this biopsy-evaluated cohort.
Recommendations
Serum ferritin can support risk stratification when interpreted with metabolic characteristics, liver enzymes, and established fibrosis assessment tools; it should not be used as an isolated diagnostic marker.
References
1. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335-1347. Doi:10.1097/HEP.0000000000000004.
Https://doi.org/10.1097/HEP.0000000000000004
2. Rinella ME, Neuschwander-Tetri BA, Siddiqui MS, Abdelmalek MF, Caldwell S, Barb D, et al. AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease. Hepatology. 2023;77(5):1797-1835. Doi:10.1097/HEP.0000000000000323.
Https://doi.org/10.1097/HEP.0000000000000323
3. 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(2):389-397.e10. Doi:10.1053/j.gastro.2015.04.043.
Https://doi.org/10.1053/j.gastro.2015.04.043
4. 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(6):1313-1321. Doi:10.1002/hep.20701.
Https://doi.org/10.1002/hep.20701
5. Von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453-1457. Doi:10.1016/S0140-6736(07)61602-X.
Https://doi.org/10.1016/S0140-6736(07)61602-X
6. Brunt EM, Kleiner DE, Wilson LA, Belt P, Neuschwander-Tetri BA; NASH Clinical Research Network. Nonalcoholic fatty liver disease activity score and the histopathologic diagnosis in NAFLD: distinct clinicopathologic meanings. Hepatology. 2011;53(3):810-820. Doi:10.1002/hep.24127.
Https://doi.org/10.1002/hep.24127
7. Kowdley KV, Belt P, Wilson LA, Yeh MM, Neuschwander-Tetri BA, Chalasani N, et al. Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease. Hepatology. 2012;55(1):77-85. Doi:10.1002/hep.24706.
Https://doi.org/10.1002/hep.24706
8. Manousou P, Kalambokis G, Grillo F, Watkins J, Xirouchakis E, Pleguezuelo M, et al. Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non-alcoholic fatty liver disease patients. Liver Int. 2011;31(5):730-739. Doi:10.1111/j.1478-3231.2011.02488.x.
Https://doi.org/10.1111/j.1478-3231.2011.02488.x
9. Fracanzani AL, Valenti L, Bugianesi E, Andreoletti M, Colli A, Vanni E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology. 2008;48(3):792-798. Doi:10.1002/hep.22429.
Https://doi.org/10.1002/hep.22429
10. Nelson JE, Wilson L, Brunt EM, Yeh MM, Kleiner DE, Unalp-Arida A, et al. Relationship between the pattern of hepatic iron deposition and histological severity in nonalcoholic fatty liver disease. Hepatology. 2011;53(2):448-457. Doi:10.1002/hep.24038.
Https://doi.org/10.1002/hep.24038
11. Parikh P, Patel J, Ingle M, Sawant P. Serum ferritin levels predict histological severity in patients with nonalcoholic fatty liver disease in India. Indian J Gastroenterol. 2015;34(3):200-208. Doi:10.1007/s12664-015-0572-5.
Https://doi.org/10.1007/s12664-015-0572-5
12. Buzzetti E, Petta S, Manuguerra R, Luong TV, Cabibi D, Corradini E, et al. Evaluating the association of serum ferritin and hepatic iron with disease severity in non-alcoholic fatty liver disease. Liver Int. 2019;39(7):1325-1334. Doi:10.1111/liv.14096.
Https://doi.org/10.1111/liv.14096
13. Angulo P, George J, Day CP, Vanni E, Russell L, De la Cruz AC, et al. Serum ferritin levels lack diagnostic accuracy for liver fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014;12(7):1163-1169.e1. Doi:10.1016/j.cgh.2013.11.035.
Https://doi.org/10.1016/j.cgh.2013.11.035
14. Trasolini R, Cox B, Galts C, Yoshida EM, Marquez V. Elevated serum ferritin in non-alcoholic fatty liver disease is not predictive of fibrosis. Can Liver J. 2022;5(2):152-159.
Https://doi.org/10.3138/canlivj-2021-0002
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Dr. Nadera Sultana, Dr. Sailusha Sreerama, Dr. Rama Shouri

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.














