Relationship between changes in serum levels of keratin 18 and changes in liver histology in children and adults with nonalcoholic fatty liver disease - PubMed (original) (raw)

. 2014 Dec;12(12):2121-30.e1-2.

doi: 10.1016/j.cgh.2014.05.010. Epub 2014 May 17.

Ajay K Jain 2, Ross Deppe 1, Katherine Yates 3, Megan Comerford 1, Howard C Masuoka 1, Brent A Neuschwander-Tetri 2, Rohit Loomba 4, Elizabeth M Brunt 5, David E Kleiner 6, Jean P Molleston 1, Jeffrey B Schwimmer 7, Joel E Lavine 8, James Tonascia 3, Naga Chalasani 9

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Relationship between changes in serum levels of keratin 18 and changes in liver histology in children and adults with nonalcoholic fatty liver disease

Raj Vuppalanchi et al. Clin Gastroenterol Hepatol. 2014 Dec.

Abstract

Background & aims: Cross-sectional studies have associated serum levels of the keratin 18 (K18) fragment with histologic features of liver in individuals with nonalcoholic fatty liver disease (NAFLD). We investigated the relationship between changes in serum levels of K18 and changes in liver histology in adults and children with NAFLD.

Methods: We measured levels of K18 in stored serum samples collected at baseline and various time points from 231 adults with nonalcoholic steatohepatitis and 152 children with NAFLD who participated in 2 separate prospective randomized clinical trials. Liver biopsy specimens collected at baseline and week 96 were reviewed centrally.

Results: There were greater decreases in serum levels of K18 in adults with histologic improvement at week 96 than in those without histologic improvement at week 16 (decrease, 193 ± 293 vs 139 ± 467 U/L; P < .001), week 48 (decrease, 232 ± 360 vs 113 ± 425 U/L; P < .001), or week 96 (decrease, 269 ± 368 vs 97 ± 400 U/L; P < .001). There were greater decreases in serum levels of K18 in children with histologic improvements than in those without histologic improvements at week 48 (decrease, 197 ± 467 vs 47 ± 350 U/L; P = .005) and week 96 (decrease, 206 ± 432 vs 2 ± 474 U/L; P < .001). However, reductions in serum levels of K18 were not better than reductions in levels of alanine aminotransferase in identifying adults with histologic improvement (area under the receiver operator characteristic [AUROC], 0.71; 95% confidence interval [CI], 0.63-0.80; vs AUROC, 0.68; 95% CI, 0.61-0.79; P = .34) or children (AUROC, 0.72; 95% CI, 0.63-0.81; vs AUROC, 0.79; 95% CI, 0.70-0.87; P = .42).

Conclusions: Decreases in serum levels of K18 are associated strongly with improved liver histologies in adults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD.

Keywords: Nonalcoholic Steatohepatitis; Noninvasive Biomarker; PIVENS; Serum K18; TONIC.

Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. Changes in serum K18 levels in the PIVENS trial

Panel A: Changes in serum K18 levels in three treatment groups (placebo, pioglitazone and vitamin E) during the PIVENS trial. Panel B: Changes in serum K18 levels in adults who achieved histological improvement as compared to those who did not achieve histological improvement in the PIVENS trial. Histological improvement was defined based on specified change in NAS and no progression of fibrosis as described in the text. Panel C: Changes in serum K18 levels in adults with and without resolution of NASH in the PIVENS trial.

Figure 2

Figure 2. Changes serum K18 fragment levels during the TONIC trial

Panel A: Changes in serum K18 levels in three treatment groups (placebo, metformin and vitamin E) during the TONIC trial. Panel B: Changes in serum K18 levels in adults who achieved histological improvement as compared to those who did not achieve histological improvement in the TONIC trial. Histological improvement was defined based on change in NAS and no progression of fibrosis as described in the text. Panel C: Changes in serum K18 levels in adults with and without resolution of NASH in the TONIC trial.

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