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 Masuoka, Brent A. Neuschwander-Tetri, Rohit Loomba, Elizabeth M. Brunt, David E. Kleiner, Jean Molleston, Jeffrey B. Schwimmer, Joel E. Lavine, James Tonascia, Naga Chalasani

Research output: Contribution to journalArticle

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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 atweek 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 inadults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD.

Original languageEnglish
Pages (from-to)2121-2130
Number of pages10
JournalClinical Gastroenterology and Hepatology
Volume12
Issue number12
DOIs
StatePublished - Dec 1 2014

Fingerprint

Keratin-18
Histology
Liver
Serum
Confidence Intervals
Alanine Transaminase
Non-alcoholic Fatty Liver Disease
Randomized Controlled Trials
Cross-Sectional Studies
Biopsy

Keywords

  • Nonalcoholic Steatohepatitis
  • Noninvasive Biomarker
  • PIVENS
  • Serum K18
  • TONIC

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology

Cite this

Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease. / Vuppalanchi, Raj; Jain, Ajay K.; Deppe, Ross; Yates, Katherine; Comerford, Megan; Masuoka, Howard; Neuschwander-Tetri, Brent A.; Loomba, Rohit; Brunt, Elizabeth M.; Kleiner, David E.; Molleston, Jean; Schwimmer, Jeffrey B.; Lavine, Joel E.; Tonascia, James; Chalasani, Naga.

In: Clinical Gastroenterology and Hepatology, Vol. 12, No. 12, 01.12.2014, p. 2121-2130.

Research output: Contribution to journalArticle

Vuppalanchi, Raj ; Jain, Ajay K. ; Deppe, Ross ; Yates, Katherine ; Comerford, Megan ; Masuoka, Howard ; Neuschwander-Tetri, Brent A. ; Loomba, Rohit ; Brunt, Elizabeth M. ; Kleiner, David E. ; Molleston, Jean ; Schwimmer, Jeffrey B. ; Lavine, Joel E. ; Tonascia, James ; Chalasani, Naga. / Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease. In: Clinical Gastroenterology and Hepatology. 2014 ; Vol. 12, No. 12. pp. 2121-2130.
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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 atweek 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 inadults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD.",
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author = "Raj Vuppalanchi and Jain, {Ajay K.} and Ross Deppe and Katherine Yates and Megan Comerford and Howard Masuoka and Neuschwander-Tetri, {Brent A.} and Rohit Loomba and Brunt, {Elizabeth M.} and Kleiner, {David E.} and Jean Molleston and Schwimmer, {Jeffrey B.} and Lavine, {Joel E.} and James Tonascia and Naga Chalasani",
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T1 - Relationship Between Changes in Serum Levels of Keratin 18 and Changes in Liver Histology in Children and Adults With Nonalcoholic Fatty Liver Disease

AU - Vuppalanchi, Raj

AU - Jain, Ajay K.

AU - Deppe, Ross

AU - Yates, Katherine

AU - Comerford, Megan

AU - Masuoka, Howard

AU - Neuschwander-Tetri, Brent A.

AU - Loomba, Rohit

AU - Brunt, Elizabeth M.

AU - Kleiner, David E.

AU - Molleston, Jean

AU - Schwimmer, Jeffrey B.

AU - Lavine, Joel E.

AU - Tonascia, James

AU - Chalasani, Naga

PY - 2014/12/1

Y1 - 2014/12/1

N2 - 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 atweek 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 inadults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD.

AB - 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 atweek 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 inadults or children with NAFLD. However, reductions in K18 do not perform better than those in alanine aminotransferase level in identifying histologic changes in NAFLD.

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