Relationship between changes in serum levels of keratin 18 and changes in liver histology in children and adults with nonalcoholic fatty liver disease.
OBJECTIVE
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.
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Raj
R
Vuppalanchi
St. Louis University, St. Louis, Missouri.
Ajay K
AK
Jain
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Ross
R
Deppe
Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
Katherine
K
Yates
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Megan
M
Comerford
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Howard C
HC
Masuoka
St. Louis University, St. Louis, Missouri.
Brent A
BA
Neuschwander-Tetri
Division of Gastroenterology, University of California, San Diego, California.
Rohit
R
Loomba
Washington University School of Medicine, St. Louis, Missouri.
Elizabeth M
EM
Brunt
Laboratory of Pathology, National Cancer Institute, Bethesda, Maryland.
David E
DE
Kleiner
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.
Jean P
JP
Molleston
Department of Pediatrics, University of California, San Diego, California; Department of Gastroenterology, Rady Children's Hospital, San Diego, California.
Jeffrey B
JB
Schwimmer
Department of Pediatrics, Columbia University, New York, New York.
Joel E
JE
Lavine
Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland.
James
J
Tonascia
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: nchalasa@iu.edu.
Naga
N
Chalasani
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D006651:Histocytochemistry; D006801:Humans; D053538:Keratin-18 / Q000097:blood*; D008099:Liver / Q000473:pathology*; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D044967:Serum / Q000737:chemistry
C488421:KRT18 protein, human; D053538:Keratin-18
Nonalcoholic Steatohepatitis; Noninvasive Biomarker; PIVENS; Serum K18; TONIC