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

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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Authors

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

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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)

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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). https://doi.org/10.1007/s11695-016-2246-5

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Keywords

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