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Relationship of ELF and PIIINP With Liver Histology and Response to Vitamin E or Pioglitazone in the PIVENS Trial

Gawrieh, S; Wilson, LA; Yates, KP; Cummings, OW; Vilar-Gomez, E; Ajmera, V; Kowdley, K; ... Chalasani, N; + view all (2021) Relationship of ELF and PIIINP With Liver Histology and Response to Vitamin E or Pioglitazone in the PIVENS Trial. Hepatology Communications , 5 (5) pp. 786-797. 10.1002/hep4.1680. Green open access

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Abstract

Enhanced liver fibrosis score (ELF) and one of its components, amino‐terminal propeptide of type III procollagen (PIIINP) are promising noninvasive biomarkers of liver histology in patients with nonalcoholic steatohepatitis (NASH). We evaluated the association of ELF and PIIINP with fibrosis stages at baseline and end of treatment (EOT) with vitamin E or pioglitazone in the PIVENS trial (Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Nondiabetic Patients With NASH) and characterized ELF and PIIINP changes and their associations with changes in the histological endpoints. ELF and PIIINP were measured at baseline and weeks 16, 48, and 96 on sera from 243 PIVENS participants. Baseline and EOT ELF were significantly associated with fibrosis stage (P < 0.001). The area under the curve for ELF’s detection of clinically significant and advanced fibrosis in baseline biopsies was 0.74 and 0.79, respectively (P < 0.001). There was a significant drop in ELF score at weeks 48 and 96 in patients who achieved the NAFLD activity score (NAS)–based primary end point (P = 0.007) but not in those who experienced NASH resolution (P = 0.24) or fibrosis improvement (P = 0.50). Change in PIIINP was significantly associated with NASH resolution and improvement in NAS‐based histological endpoint and fibrosis (P < 0.05 for all). Over the study period, both ELF and PIIINP significantly decreased with vitamin E (P < 0.05), but only PIIINP decreased with pioglitazone (P < 0.001). Conclusion: ELF is significantly associated with clinically significant and advanced fibrosis in patients with NASH, but its longitudinal changes were not associated with improvement in fibrosis or NASH resolution. PIIINP, one of its components, appears promising for identifying longitudinal histologic changes in patients with NASH and is worthy of further investigation.

Type: Article
Title: Relationship of ELF and PIIINP With Liver Histology and Response to Vitamin E or Pioglitazone in the PIVENS Trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/hep4.1680
Publisher version: https://doi.org/10.1002/hep4.1680
Language: English
Additional information: Copyright © 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
URI: https://discovery.ucl.ac.uk/id/eprint/10123031
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