Diagnostic accuracy of noninvasive fibrosis models to detect change in fibrosis stage
Open accessAbstract
Background & aims Noninvasive methods are needed to determine disease stage in patients with nonalcoholic fatty liver disease (NAFLD). We evaluated the diagnostic performance of several widely available fibrosis models for the assessment of hepatic fibrosis in patients with NAFLD.Methods We performed a retrospective analysis of data from individuals enrolled in the NIDDK NASH Clinical Research Network, from 2004 through 2018. Using biopsy as the reference standard, we determined the diagnostic performance of the aspartate aminotransferase (AST):platelet ratio (APRI), FIB-4, ratio of AST:alanine aminotransferase (ALT) and the NAFLD fibrosis score (NFS) in a cross-sectional study of 1904 subjects. The ability of these models to detect changes in fibrosis stage was assessed in a longitudinal data set of 292 subjects with 2 biopsies and accompanying laboratory data. Outcomes were detection of fibrosis of any stage (stages 0-4), detection of moderate fibrosis (stages 0-1 vs 2-4), and detection of advanced fibrosis (stages 0-2 vs 3-4). Diagnostic performance was evaluated using the C-statistic, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) analyses.Results In the cross-sectional study, FIB-4 and NFS outperformed other non-invasive models for detecting advanced fibrosis; the C-statistics were 0.80 for FIB-4 and 0.78 for NFS. In the longitudinal study, 216 patients had non-advanced fibrosis at baseline and 35 patients progressed to advanced fibrosis after median follow up of 2.6 years. After we adjusted for fibrosis stage and model score at initial biopsy, change in APRI, FIB-4, and NFS were significantly associated with change in fibrosis. A unit change in APRI, FIB-4, or NFS was associated with changes in fibrosis stage of 0.33 (95% CI, 0.20-0.45; P < .001), 0.26 (95% CI, 0.15-0.37; P < .001), and 0.19 (95% CI, 0.07-0.31; P = .002), respectively. The cross-validated C-statistic for detecting progression to advanced fibrosis for APRI was 0.82 (95% CI, 0.74-0.89), for FIB-4 was 0.81 (95% CI, 0.73-0.81), and for NFS was 0.80 (95% CI, 0.71-0.88).Conclusions In a combined analysis of data from 2 large studies, we found that FIB-4, APRI, and NFS can detect advanced fibrosis and fibrosis progression in patients with NAFLD.
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In a retrospective longitudinal study with paired liver biopsies, the increase over time of APRI, FIB-4 and NFS was significantly associated with one-stage fibrosis progression, with cross-validated C-statistic > 0.80.
“In a retrospective longitudinal study with paired liver biopsies (median time interval: 2.6 years), the increase over time of APRI, FIB-4 and NFS was signi fi cantly associated with onestage fi brosis progression (cross-validated C-statistic > 0.80).”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [175]
The Methods and Longitudinal Assessment sections describe a retrospective study with paired biopsies a median of 2.6 years apart. The Results report significant associations between changes in APRI, FIB-4 and NFS and changes in fibrosis stage. However, the cross-validated C-statistics of 0.82, 0.81 and 0.80 concern progression to advanced fibrosis, not one-stage progression; NFS is 0.80, not greater than 0.80. (LLM, conf=0.90)
Experimental — accuracy not yet measuredFIB-4 and NFS had high negative predictive values around 90%, but suboptimal positive predictive values for predicting progression to advanced fibrosis.
“FIB-4 and NFS had high negative predictive values (around 90%), but suboptimal positive predictive values for predicting progression to advanced fi brosis.”
From EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). (2024) · cites this paper as [175]
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References 16 · Cited by 272
Research works printed but not linked: 2
- [14]Siddiqui MS, Patidar KR, Boyett S, Performance of Non-invasive Models of Fibrosis in Predicting Mild to Moderate Fibrosis in Patients with Nonalcoholic Fatty Liver Disease (NAFLD). Liver Int 2015. 26713759
- [16]Sheth SG, Flamm SL, Gordon FD, AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol 1998; 93: 44– 48. 9448172
- Authors
- Siddiqui, M. S., Yamada, G., Vuppalanchi, R., Van Natta, M., Loomba, R., Guy, C., Brandman, D., Tonascia, J., Chalasani, N., Neuschwander-Tetri, B., Sanyal, A. J., Allende, D., Dasarathy, S., McCullough, A. J., Penumatsa, R., Dasarathy, J., Lavine, J. E., Abdelmalek, M. F., Bashir, M., Buie, S., Diehl, A. M., Guy, C., Kigongo, C., Kopping, M., Malik, D., Piercy, D., Chalasani, N., Cummings, O. W., Gawrieh, S., Ragozzino, L., Sandrasegaran, K., Vuppalanchi, R., Brunt, E. M., Cattoor, T., Carpenter, D., Freebersyser, J., King, D., Lai, J., Neuschwander-Tetri, B. A., Siegner, J., Stewart, S., Torretta, S., Wriston, K., Gonzalez, M. C., Davila, J., Jhaveri, M., Kowdley, K. V., Mukhtar, N., Ness, E., Poitevin, M., Quist, B., Soo, S., Ang, B., Behling, C., Bhatt, A., Loomba, R., Middleton, M. S., Sirlin, C., Akhter, M. F., Bass, N. M., Brandman, D., Gill, R., Hameed, B., Maher, J., Terrault, N., Ungermann, A., Yeh, M., Boyett, S., Contos, M. J., Kirwin, S., Luketic, V. A. C., Puri, P., Sanyal, A. J., Schlosser, J., Siddiqui, M. S., Yost-Schomer, L., Brunt, E. M., Fowler, K., Kleiner, D. E., Doo, E. C., Hall, S., Hoofnagle, J. H., Lee, J. J., Robuck, P. R., Sherker, A. H., Torrance, R., Belt, P., Clark, J. M., Dodge, J., Donithan, M., Hallinan, E., Isaacson, M., Lazo, M., Meinert, J., Miriel, L., Smith, J., Smith, M., Sternberg, A., Tonascia, J., Van Natta, M. L., Wagoner, A., Wilson, L. A., Yamada, G., & Yates, K.
- Affiliations
- University of California, San Francisco (US)
- Duke University (US)
- ORCID
- Neuschwander-Tetri, Brent
- Allende, Daniela
- Dasarathy, Srinivasan
- McCullough, Arthur J.
- Lavine, Joel E.
- Abdelmalek, Manal F.
- Bashir, Mustafa
- Diehl, Anna Mae
- Piercy, Dawn
- Cummings, Oscar W.
- Gawrieh, Samer
- Carpenter, Danielle
- Lai, Jinping
- Stewart, Susan
- Kowdley, Kris V.
- Behling, Cynthia
- Middleton, Michael S.
- Sirlin, Claude
- Akhter, Maheen F.
- Gill, Ryan
- Hameed, Bilal
- Terrault, Norah
- Yeh, Matthew
- Luketic, Velimir A.C.
- Fowler, Kathryn
- Kleiner, David E.
- Doo, Edward C.
- Lee, Jessica J.
- Sherker, Averell H.
- Clark, Jeanne M.
- Lazo, Mariana
- Miriel, Laura
- Smith, Michael
- Wilson, Laura A.
- Yates, Katherine
- Venue
- Clinical Gastroenterology and Hepatology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 17
- Issue
- 9
- Pages
- 1877-1885.e5
- ISSN
- 1542-3565 (ISSN-L)
- PMC
- PMC6609497
- OpenAlex
- W2907749909
- Cited by
- 272
- References
- 16
- Citations by year
- 2026: 21 · 2025: 47 · 2024: 53 · 2023: 35 · 2022: 37 · 2021: 29 · 2020: 40 · 2019: 9
- FWCI
- 21.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Clinical Gastroenterology and Hepatology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK061713, U01DK061728, U01DK061732, U01DK061734, U01DK061718, U01DK061731, U01DK061730, U01DK061738, U01DK061737)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver Disease and Transplantation
- Keywords
- non-alcoholic fatty liver disease, liver fibrosis, FIB-4, NAFLD fibrosis score, APRI, fibrosis progression, diagnostic accuracy, liver biopsy, longitudinal follow-up
- MeSH terms
- Adult, Alanine Transaminase, Aspartate Aminotransferases, Biopsy, Female, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Platelet Count, Predictive Value of Tests, Retrospective Studies, Sensitivity and Specificity, Severity of Illness Index, Disease Progression, Non-alcoholic Fatty Liver Disease
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