Relationship of ELF and PIIINP With Liver Histology and Response to Vitamin E or Pioglitazone in the PIVENS Trial - PubMed (original) (raw)

. 2021 Feb 5;5(5):786-797.

doi: 10.1002/hep4.1680. eCollection 2021 May.

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

Samer Gawrieh et al. Hepatol Commun. 2021.

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.

© 2021 The Authors. Hepatology Communications published by Wiley Periodicals LLC on behalf of the American Association for the Study of Liver Diseases.

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Figures

FIG. 1

FIG. 1

Changes in serum ELF score in the PIVENS trial. (A) Changes in serum ELF score in three treatment groups (placebo, pioglitazone, and vitamin E). The adjusted mean values of changes from baseline in serum ELF score during treatment with pioglitazone, vitamin E, or placebo over 96 weeks are shown. Error bars show 95% CIs. P values for the overall treatment effects (pioglitazone vs. placebo and vitamin E vs. placebo) on change in ELF score over time were derived from generalized estimating equation linear regression, modeling change as a function of treatment group indicators, visit code indicators, baseline ELF score, and treatment group by visit code interaction terms. (B) Changes in serum ELF score in adults who achieved NAS‐based histologic endpoint compared with those who did not achieve that histologic endpoint. The adjusted mean values of changes from baseline in serum ELF score over 96 weeks are shown. Error bars show 95% CIs. P values for the overall association between histologic improvement and change in ELF score over time were derived from generalized estimating equation linear regression, modeling change as a function of histologic improvement, visit code indicators, baseline ELF score, treatment group indicators, and histologic improvement by visit code interaction terms. (C) Changes in serum ELF score in adults with and without resolution of NASH. The adjusted mean values of changes from baseline in serum ELF score over 96 weeks are shown. Error bars show 95% CIs. P values for the overall association between resolution of NASH and change in ELF score over time were derived from generalized estimating equation linear regression, modeling change as a function of resolution of NASH, visit code indicators, baseline ELF score, treatment group indicators, and resolution of NASH by visit code interaction terms. (D) Changes in ELF score in adults with or without ≥1‐point improvement in fibrosis (biopsies with no fibrosis at baseline counted as not improved). The adjusted mean values of changes from baseline in serum ELF score over 96 weeks are shown. Error bars show 95% CIs. P values for the overall association between fibrosis improvement and change in ELF score over time were derived from generalized estimating equation linear regression, modeling change as a function of fibrosis improvement, visit code indicators, baseline ELF score, treatment group indicators, and fibrosis improvement by visit code interaction terms.

FIG. 2

FIG. 2

PIIINP change per treatment arm and histological endpoints in the PIVENS trial. (A) Change in PIIINP by treatment group. (B) Change in PIIINP by NAS responder versus nonresponder. (C) Changes in PIIINP in adults with and without resolution of NASH. (D) Changes in PIIINP in adults with or without ≥1‐point improvement in fibrosis (biopsies with no fibrosis at baseline counted as not improved). NAS responder was defined as ≥2‐point decrease in NAS from baseline to 96 weeks.

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