Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage

NASH CLINICAL RESEARCH NETWORK

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
JournalClinical Gastroenterology and Hepatology
DOIs
StatePublished - Jan 1 2019

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Fibrosis
Blood Platelets
Aspartate Aminotransferases
Biopsy
National Institute of Diabetes and Digestive and Kidney Diseases (U.S.)
Cross-Sectional Studies
Non-alcoholic Fatty Liver Disease
Alanine Transaminase
Liver Cirrhosis
Longitudinal Studies

Keywords

  • Diagnostic
  • Nonalcoholic Steatohepatitis
  • Prognostic
  • Scoring System Comparison

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage. / NASH CLINICAL RESEARCH NETWORK.

In: Clinical Gastroenterology and Hepatology, 01.01.2019.

Research output: Contribution to journalArticle

@article{778842724fb944c6bff17b2b60fbd3a2,
title = "Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage",
abstract = "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.",
keywords = "Diagnostic, Nonalcoholic Steatohepatitis, Prognostic, Scoring System Comparison",
author = "{NASH CLINICAL RESEARCH NETWORK} and Siddiqui, {Mohammad Shadab} and Goro Yamada and Raj Vuppalanchi and {Van Natta}, Mark and Rohit Loomba and Cynthia Guy and Danielle Brandman and James Tonascia and Naga Chalasani and Brent Neuschwander-Tetri and Sanyal, {Arun J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.cgh.2018.12.031",
language = "English (US)",
journal = "Clinical Gastroenterology and Hepatology",
issn = "1542-3565",
publisher = "W.B. Saunders Ltd",

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TY - JOUR

T1 - Diagnostic Accuracy of Noninvasive Fibrosis Models to Detect Change in Fibrosis Stage

AU - NASH CLINICAL RESEARCH NETWORK

AU - Siddiqui, Mohammad Shadab

AU - Yamada, Goro

AU - Vuppalanchi, Raj

AU - Van Natta, Mark

AU - Loomba, Rohit

AU - Guy, Cynthia

AU - Brandman, Danielle

AU - Tonascia, James

AU - Chalasani, Naga

AU - Neuschwander-Tetri, Brent

AU - Sanyal, Arun J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

KW - Diagnostic

KW - Nonalcoholic Steatohepatitis

KW - Prognostic

KW - Scoring System Comparison

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U2 - 10.1016/j.cgh.2018.12.031

DO - 10.1016/j.cgh.2018.12.031

M3 - Article

C2 - 30616027

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JO - Clinical Gastroenterology and Hepatology

JF - Clinical Gastroenterology and Hepatology

SN - 1542-3565

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