Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis

Naga Chalasani, Manal F. Abdelmalek, Rohit Loomba, Kris V. Kowdley, Arthur J. McCullough, Srinivasan Dasarathy, Brent A. Neuschwander-Tetri, Norah Terrault, Beatrice Ferguson, Reshma Shringarpure, David Shapiro, Arun J. Sanyal

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background & Aims: Non-invasive biomarkers are needed for monitoring changes in liver histology in patients with non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) was shown to improve fibrosis in patients with NASH in the FLINT trial; a post hoc analysis of these data was performed to determine the relationship between 3 non-invasive fibrosis markers and liver fibrosis improvement. Methods: In the Phase 2b FLINT trial, patients were randomised (1:1) to receive 25 mg OCA or placebo once daily for 72 weeks. Aspartate aminotransferase:platelet ratio index (APRI), fibrosis-4 (FIB-4) index and non-alcoholic fatty liver disease fibrosis score (NFS) were evaluated in serum at baseline and weeks 24, 48, 72 and 96. Liver biopsies were obtained at baseline and 72 weeks. Results: In patients with fibrosis improvement at week 24, scores were reduced by a median of 34% for APRI, 10% for FIB-4 and 4% for NFS. Reductions in APRI (P = 0.015) and FIB-4 (P = 0.036), but not NFS (P = 0.201) at week 24, significantly correlated with ≥1-stage improvement in histologic fibrosis at week 72. Reductions in APRI at week 72 were significantly correlated with fibrosis improvement at week 72 (P = 0.012). Patients receiving OCA had significant reductions in all markers compared with patients receiving placebo at week 72 [APRI and FIB-4 (P < 0.0001); NFS (P < 0.05)]. Conclusions: Readily available non-invasive markers may predict improvement in liver fibrosis in patients with NASH. Upon external confirmation and further refinement in larger populations, these markers may serve as surrogate endpoints in NASH clinical trials.

Original languageEnglish (US)
Pages (from-to)924-932
Number of pages9
JournalLiver International
Volume39
Issue number5
DOIs
StatePublished - May 1 2019

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Fatty Liver
Fibrosis
Biomarkers
Transaminases
Blood Platelets
Liver Cirrhosis
Placebos
Liver
Aspartate Aminotransferases
Histology
Clinical Trials
Biopsy
Serum

Keywords

  • biomarkers
  • fibrosis
  • non-alcoholic steatohepatitis
  • non-invasive

ASJC Scopus subject areas

  • Hepatology

Cite this

Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis. / Chalasani, Naga; Abdelmalek, Manal F.; Loomba, Rohit; Kowdley, Kris V.; McCullough, Arthur J.; Dasarathy, Srinivasan; Neuschwander-Tetri, Brent A.; Terrault, Norah; Ferguson, Beatrice; Shringarpure, Reshma; Shapiro, David; Sanyal, Arun J.

In: Liver International, Vol. 39, No. 5, 01.05.2019, p. 924-932.

Research output: Contribution to journalArticle

Chalasani, N, Abdelmalek, MF, Loomba, R, Kowdley, KV, McCullough, AJ, Dasarathy, S, Neuschwander-Tetri, BA, Terrault, N, Ferguson, B, Shringarpure, R, Shapiro, D & Sanyal, AJ 2019, 'Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis', Liver International, vol. 39, no. 5, pp. 924-932. https://doi.org/10.1111/liv.13974
Chalasani, Naga ; Abdelmalek, Manal F. ; Loomba, Rohit ; Kowdley, Kris V. ; McCullough, Arthur J. ; Dasarathy, Srinivasan ; Neuschwander-Tetri, Brent A. ; Terrault, Norah ; Ferguson, Beatrice ; Shringarpure, Reshma ; Shapiro, David ; Sanyal, Arun J. / Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis. In: Liver International. 2019 ; Vol. 39, No. 5. pp. 924-932.
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abstract = "Background & Aims: Non-invasive biomarkers are needed for monitoring changes in liver histology in patients with non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) was shown to improve fibrosis in patients with NASH in the FLINT trial; a post hoc analysis of these data was performed to determine the relationship between 3 non-invasive fibrosis markers and liver fibrosis improvement. Methods: In the Phase 2b FLINT trial, patients were randomised (1:1) to receive 25 mg OCA or placebo once daily for 72 weeks. Aspartate aminotransferase:platelet ratio index (APRI), fibrosis-4 (FIB-4) index and non-alcoholic fatty liver disease fibrosis score (NFS) were evaluated in serum at baseline and weeks 24, 48, 72 and 96. Liver biopsies were obtained at baseline and 72 weeks. Results: In patients with fibrosis improvement at week 24, scores were reduced by a median of 34{\%} for APRI, 10{\%} for FIB-4 and 4{\%} for NFS. Reductions in APRI (P = 0.015) and FIB-4 (P = 0.036), but not NFS (P = 0.201) at week 24, significantly correlated with ≥1-stage improvement in histologic fibrosis at week 72. Reductions in APRI at week 72 were significantly correlated with fibrosis improvement at week 72 (P = 0.012). Patients receiving OCA had significant reductions in all markers compared with patients receiving placebo at week 72 [APRI and FIB-4 (P < 0.0001); NFS (P < 0.05)]. Conclusions: Readily available non-invasive markers may predict improvement in liver fibrosis in patients with NASH. Upon external confirmation and further refinement in larger populations, these markers may serve as surrogate endpoints in NASH clinical trials.",
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T1 - Relationship between three commonly used non-invasive fibrosis biomarkers and improvement in fibrosis stage in patients with non-alcoholic steatohepatitis

AU - Chalasani, Naga

AU - Abdelmalek, Manal F.

AU - Loomba, Rohit

AU - Kowdley, Kris V.

AU - McCullough, Arthur J.

AU - Dasarathy, Srinivasan

AU - Neuschwander-Tetri, Brent A.

AU - Terrault, Norah

AU - Ferguson, Beatrice

AU - Shringarpure, Reshma

AU - Shapiro, David

AU - Sanyal, Arun J.

PY - 2019/5/1

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N2 - Background & Aims: Non-invasive biomarkers are needed for monitoring changes in liver histology in patients with non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) was shown to improve fibrosis in patients with NASH in the FLINT trial; a post hoc analysis of these data was performed to determine the relationship between 3 non-invasive fibrosis markers and liver fibrosis improvement. Methods: In the Phase 2b FLINT trial, patients were randomised (1:1) to receive 25 mg OCA or placebo once daily for 72 weeks. Aspartate aminotransferase:platelet ratio index (APRI), fibrosis-4 (FIB-4) index and non-alcoholic fatty liver disease fibrosis score (NFS) were evaluated in serum at baseline and weeks 24, 48, 72 and 96. Liver biopsies were obtained at baseline and 72 weeks. Results: In patients with fibrosis improvement at week 24, scores were reduced by a median of 34% for APRI, 10% for FIB-4 and 4% for NFS. Reductions in APRI (P = 0.015) and FIB-4 (P = 0.036), but not NFS (P = 0.201) at week 24, significantly correlated with ≥1-stage improvement in histologic fibrosis at week 72. Reductions in APRI at week 72 were significantly correlated with fibrosis improvement at week 72 (P = 0.012). Patients receiving OCA had significant reductions in all markers compared with patients receiving placebo at week 72 [APRI and FIB-4 (P < 0.0001); NFS (P < 0.05)]. Conclusions: Readily available non-invasive markers may predict improvement in liver fibrosis in patients with NASH. Upon external confirmation and further refinement in larger populations, these markers may serve as surrogate endpoints in NASH clinical trials.

AB - Background & Aims: Non-invasive biomarkers are needed for monitoring changes in liver histology in patients with non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) was shown to improve fibrosis in patients with NASH in the FLINT trial; a post hoc analysis of these data was performed to determine the relationship between 3 non-invasive fibrosis markers and liver fibrosis improvement. Methods: In the Phase 2b FLINT trial, patients were randomised (1:1) to receive 25 mg OCA or placebo once daily for 72 weeks. Aspartate aminotransferase:platelet ratio index (APRI), fibrosis-4 (FIB-4) index and non-alcoholic fatty liver disease fibrosis score (NFS) were evaluated in serum at baseline and weeks 24, 48, 72 and 96. Liver biopsies were obtained at baseline and 72 weeks. Results: In patients with fibrosis improvement at week 24, scores were reduced by a median of 34% for APRI, 10% for FIB-4 and 4% for NFS. Reductions in APRI (P = 0.015) and FIB-4 (P = 0.036), but not NFS (P = 0.201) at week 24, significantly correlated with ≥1-stage improvement in histologic fibrosis at week 72. Reductions in APRI at week 72 were significantly correlated with fibrosis improvement at week 72 (P = 0.012). Patients receiving OCA had significant reductions in all markers compared with patients receiving placebo at week 72 [APRI and FIB-4 (P < 0.0001); NFS (P < 0.05)]. Conclusions: Readily available non-invasive markers may predict improvement in liver fibrosis in patients with NASH. Upon external confirmation and further refinement in larger populations, these markers may serve as surrogate endpoints in NASH clinical trials.

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