Modified thresholds for fibrosis risk scores in nonalcoholic fatty liver disease are necessary in the obese



Obesity and its related comorbidities are significant risk factors for nonalcoholic fatty liver disease (NAFLD). Liver fibrosis is the major determinant of long-term outcomes in NAFLD. A non-invasive tool that accurately identifies obese patients at elevated risk of liver fibrosis would be of significant value. Fibrosis risk scores in patients with NAFLD have been proposed but have not been validated in obese populations. We aimed to validate established simple fibrosis scores in bariatric surgical patients.


We conducted a prospective study of 107 consecutive high-risk obese patients undergoing primary bariatric surgery. Proposed fibrosis scores (NAFLD fibrosis score; body mass index (BMI), aspartate aminotransferase (AST)/alanine aminotransferase ratio (ALT), and diabetes (BARD); Fibrosis-4 (FIB-4); Forn; and AST to platelet ratio index) were calculated and compared hepatic fibrosis determined by histology of intraoperative liver biopsies. Accuracy was determined, and fibrosis score thresholds were optimized. These modified thresholds were then validated in an independent bariatric surgical population.


Liver biopsies were available in 101 patients. Sixty-eight patients had some degree of fibrosis, with 23 patients (23 %) having significant fibrosis (F2–4). The Forn score best predicted significant fibrosis (area under the receiver operator characteristic curve (AUROC) 0.724, p = 0.001). With standard thresholds, the sensitivity for the Forn score for identification of significant fibrosis (F2–4) was 0 %. Using modified thresholds of 3.5, the sensitivity and negative predictive value increased to 85.7 and 94.7 %. This threshold was applied to an independent validation cohort with good accuracy.


Fibrosis risk scores using simple markers have moderate success at delineating obese patients with significant NAFLD-related fibrosis. Thresholds, however, need to be lowered to maximize diagnostic accuracy in this cohort.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2


  1. 1.

    Gholam P, Kotler D, Flancbaum L. Liver pathology in morbidly obese patients undergoing Roux-en-Y gastric bypass surgery. Obes Surg. 2002;12:49–51.

    Article  PubMed  Google Scholar 

  2. 2.

    Abrams GA, Kunde SS, Lazenby AJ, et al. Portal fibrosis and hepatic steatosis in morbidly obese subjects: a spectrum of nonalcoholic fatty liver disease. Hepatology. 2004;40:475–83.

    Article  PubMed  Google Scholar 

  3. 3.

    Ratziu V, Giral P, Charlotte F, et al. Liver fibrosis in overweight patients. Gastroenterology. 2000;118:1117–23.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    Feijo SG, Lima JM, Oliveira MA, et al. The spectrum of non alcoholic fatty liver disease in morbidly obese patients: prevalence and associate risk factors. Acta Cir Bras. 2013;28(11):788–93.

    Article  PubMed  Google Scholar 

  5. 5.

    Angulo P, Kleiner DE, Dam-Larsen S, 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.

    Article  PubMed  PubMed Central  Google Scholar 

  6. 6.

    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.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34:274–85.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Milic S, Stimac D. Nonalcoholic fatty liver disease/steatohepatitis: epidemiology, pathogenesis, clinical presentation and treatment. Dig Dis. 2012;30:158–62.

    Article  PubMed  Google Scholar 

  9. 9.

    Kleiner DE, Berk PD, Hsu JY, et al. Hepatic pathology among patients with known liver disease undergoing bariatric surgery: observations and a perspective from the Longitudinal Assessment of Bariatric Surgery (LABS) study. Semin Liver Dis. 2014;34(1):98–107.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Sumida Y, Nakajima A, Itoh Y. Limitations of liver biopsy and non-invasive diagnostic tests for the diagnosis of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World J Hepatol. 2014;20(2):475–85.

    Google Scholar 

  11. 11.

    Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999;30:1356–62.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    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.

    CAS  Article  PubMed  Google Scholar 

  13. 13.

    Morita S, Neto DDS, Morita FHA, et al. Prevalence of non-alcoholic fatty liver disease and steatohepatitis risk factors in patients undergoing bariatric surgery. Obes Surg. 2015;25(12):2335–43.

    Article  PubMed  Google Scholar 

  14. 14.

    Abd El-Rihim AY, Omar RF, Fathalah W, et al. Role of fibroscan and APRI in detection of liver fibrosis: a systematic review and meta-analysis. Arab J Gastroenterol. 2013;14:44–50.

    Article  PubMed  Google Scholar 

  15. 15.

    Kruger FC, Daniels CR, Kidd M, et al. APRI: A simple bedside marker for advanced fibrosis that can avoid liver biopsy in patients with NAFLD/NASH. S Afr Med J. 2011;101(7):477–80.

    CAS  PubMed  Google Scholar 

  16. 16.

    Subasi CF, Aykut UE, Yilmaz Y. Comparison of noninvasive scores for the detection of advanced fibrosis in patients with nonalcoholic fatty liver disease. Eur J Gastroenterol Hepatol. 2015;27(2):137–41.

    Article  PubMed  Google Scholar 

  17. 17.

    Angulo P, Hui JM, Marchesini G, et al. The NAFLD fibrosis score: a noninvasive system that identifies liver fibrosis in patients with NAFLD. Hepatology. 2007;45(4):846–54.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Harrison SA, Oliver D, Arnold HL, et al. Development and validation of a simple NAFLD clinical scoring system for identifying patients without advanced disease. Gut. 2008;57(10):1441–7.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Raszeja-Wyszomirska J, Szymanik B, Lawniczak M, et al. Validation of the BARD scoring system in Polish patients with nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol. 2010;10:67.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Kim D, Kim WR, Talwalkar JA, et al. Advanced fibrosis in nonalcoholic fatty liver disease: noninvasive assessment with MR elastography. Radiology. 2013;268(2):411–9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Shah AG, Lydecker A, Murray K, et al. Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2009;7(10):1104–12.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Ruffillo G, Fassio E, Alvarez E, et al. Comparison of NAFLD fibrosis score and BARD score in predicting fibrosis in nonalcoholic fatty liver disease. J Hepatol. 2011;54(1):160–3.

    Article  PubMed  Google Scholar 

  23. 23.

    Francque S, Verrijken A, Mertens I, et al. Design and validation of routine parameters-based scores and comparison with established scores for prospective assessment of steatohepatitis in patients at risk: a large single-centre study. Obesity Facts. 2012;5:85.

    Google Scholar 

  24. 24.

    Cui J, Ang B, Haufe W, et al. Comparative diagnostic accuracy of magnetic resonance elastography vs. eight clinical prediction rules for non-invasive diagnosis of advanced fibrosis in biopsy-proven non-alcoholic fatty liver disease: a prospective study. Aliment Pharmacol Ther. 2015;41(12):1271–80.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Demir M, Lang S, Schlattjan M, et al. NIKEI: a new inexpensive and non-invasive scoring system to exclude advanced fibrosis in patients with NAFLD. PLoS One. 2013;8(3):e58360.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    Lassailly G, Caiazzo R, Buob D, et al. Bariatric surgery reduces features of nonalcoholic steatohepatitis in morbidly obese patients. Gastroenterology. 2015;149:379–88.

    Article  PubMed  Google Scholar 

  27. 27.

    Shalhub S, Parsee A, Gallagher SF, et al. The importance of routine liver biopsy in diagnosing nonalcoholic steatohepatitis in bariatric patients. Obes Surg. 2004;14(1):54–9.

    Article  PubMed  Google Scholar 

  28. 28.

    Alberti KGMM, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A consensus statement from the International Diabetes Federation. Diabet Med. 2006;23:469–80.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology. Gastroenterology. 2012;142(7):1592–609.

    Article  PubMed  Google Scholar 

  30. 30.

    Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.

    Article  PubMed  Google Scholar 

  31. 31.

    Lumeng CN, Bodzin JL, Saltiel AR. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest. 2007;117(1):175–84.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Olefsky JM, Glass CK. Macrophages, inflammation and insulin resistance. Annu Rev Physiol. 2010;72:219–46.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Aykut UE, Akyuz U, Yesil A, et al. A comparison of FibroMeter NAFLD Score, NAFLD fibrosis score, and transient elastography as noninvasive diagnostic tools for hepatic fibrosis in patients with biopsy-proven non-alcoholic fatty liver disease. Scand J Gastroenterol. 2014;49(11):1343–8.

    PubMed  Google Scholar 

  34. 34.

    Dvorak K, Stritesky J, Petrtyl J, et al. Use of non-invasive parameters of non-alcoholic steatohepatitis and liver fibrosis in daily practice—An exploratory case-control study. PLoS One. 2014;9(10):e111551. doi:10.1371/journal.pone.0111551. 1–10.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Geraldine J. Ooi.

Ethics declarations

Conflict of interest

The Centre for Obesity Research and Education has received funding for research purposes from Allergan, Inc., the manufacturer of the LAP-BAND. Prof. Cowley reports grants and personal fees from Novo Nordisk and personal fees and other from Orexigen Therapeutics outside the submitted work; Prof. Brown reports financial support for a bariatric surgery registry from the Commonwealth of Australia, Apollo Endosurgery, Covidien, Johnson and Johnson, Gore and Applied Medical. Dr. Ooi and Dr. Doyle report scholarships from the National Health and Medical Research Council and the Royal Australasian College of Surgeons. Mr. Burton, Prof. Wentworth, Prof. Bhathal, Prof. Sikaris, Prof. Roberts, Dr. Kemp, and Prof. O’Brien have no disclosures or conflicts of interest.

Ethical standards

This manuscript (in part or full) has not been published previously and is not currently submitted for consideration elsewhere. All participants in this study provided informed written consent prior to enrolment. Two local institute human research and ethics committees have approved the study, and both comply with standards as per the Declaration of Helsinki. 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. This study was registered in the Australian New Zealand Clinical Trials Registry.

Author contributions

All listed authors have contributed to and agree upon the content of the final manuscript. All authors contributed to study conception and design. Authors 1, 2, 3, 5, 10, and 11 were involved in data acquisition. Authors 1, 2, 5, 6, 8, 9, and 11 performed data analyses. All authors drafted and/or revised the manuscript.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Figure S1

AUROC for scores for identification of advanced fibrosis (F3–4) in the training cohort. (DOCX 3391 kb)

Figure S2

Box plots scores for training and validation cohorts divided into F0–2 vs F3–4 fibrosis. Standard thresholds (solid line) and optimized thresholds (dotted line) shown. (DOCX 4736 kb)

Table S1

Sensitivity, specificity, PPV, and NPV for scores using standard high cutoff points for classification of advanced fibrosis (F3–4) using standard cutoff values (left) and modified cutoff values (right) calculated from threshold that gives the highest Youden index. (DOCX 39 kb)

Table S2

Sensitivity, specificity, PPV, and NPV for scores using modified cutoff values for classification of advanced fibrosis (F3–4) in the validation cohort. (DOCX 38 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ooi, G.J., Burton, P.R., Doyle, L. et al. Modified thresholds for fibrosis risk scores in nonalcoholic fatty liver disease are necessary in the obese. OBES SURG 27, 115–125 (2017).

Download citation


  • Fibrosis risk scores, NAFLD fibrosis score, FIB
  • 4, BARD, APRI, Forn score
  • Nonalcoholic fatty liver disease
  • Obesity
  • Sensitivity and specificity