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; Ajay K Jain; Ross Deppe; Katherine Yates; Megan Comerford; Howard C Masuoka; Brent A Neuschwander-Tetri; Rohit Loomba; Elizabeth M Brunt; David E Kleiner; Jean P Molleston; Jeffrey B Schwimmer; Joel E Lavine; James Tonascia; Naga Chalasani

doi:10.1016/j.cgh.2014.05.010

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

Clin Gastroenterol Hepatol. 2014 Dec;12(12):2121-30.e1-2. doi: 10.1016/j.cgh.2014.05.010. Epub 2014 May 17.

Authors

Affiliations

¹ Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
² St. Louis University, St. Louis, Missouri.
³ Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
⁴ Division of Gastroenterology, University of California, San Diego, California.
⁵ Washington University School of Medicine, St. Louis, Missouri.
⁶ Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
⁷ Department of Pediatrics, University of California, San Diego, California; Department of Gastroenterology, Rady Children's Hospital, San Diego, California.
⁸ Department of Pediatrics, Columbia University, New York, New York.
⁹ Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: nchalasa@iu.edu.

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.

Publication types

Research Support, American Recovery and Reinvestment Act
Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Adult
Biopsy
Child
Histocytochemistry
Humans
Keratin-18 / blood*
Liver / pathology*
Non-alcoholic Fatty Liver Disease / pathology*
Randomized Controlled Trials as Topic
Serum / chemistry

Substances

KRT18 protein, human
Keratin-18

Abstract

Publication types

MeSH terms

Substances

Grants and funding