Plasma cathepsin D levels: A novel tool to predict pediatric hepatic inflammation

Sofie M A Walenbergh, Tom Houben, Tim Hendrikx, Mike L J Jeurissen, Patrick J. Van Gorp, Anita C E Vreugdenhil, Marlou P. Adriaanse, Wim A. Buurman, Marten H. Hofker, Antonella Mosca, Patrick J. Lindsey, Anna Alisi, Daniela Liccardo, Nadia Panera, Ger H. Koek, Valerio Nobili, Ronit Shiri-Sverdlov

Research output: Contribution to journalArticle

Abstract

OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is the most severe form of a hepatic condition known as nonalcoholic fatty liver disease (NAFLD). NASH is histologically characterized by hepatic fat accumulation, inflammation, and ballooning, and eventually coupled with fibrosis that, in turn, may progress to end-stage liver disease even in young individuals. Hence, there is a critical need for specific noninvasive markers to predict hepatic inflammation at an early age. We investigated whether plasma levels of cathepsin D (CatD), a lysosomal protease, correlated with the severity of liver inflammation in pediatric NAFLD.METHODS:Liver biopsies from children (n=96) with NAFLD were histologically evaluated according to the criteria of Kleiner (NAFLD activity score) and the Brunt's criteria. At the time of liver biopsy, blood was taken and levels of CatD, alanine aminotransferase (ALT), and cytokeratin-18 (CK-18) were measured in plasma.RESULTS:Plasma CatD levels were significantly lower in subjects with liver inflammation compared with steatotic subjects. Furthermore, we found that CatD levels were gradually reduced and corresponded with increasing severity of liver inflammation, steatosis, hepatocellular ballooning, and NAFLD activity score. CatD levels correlated with pediatric NAFLD disease progression better than ALT and CK-18. In particular, CatD showed a high diagnostic accuracy (area under receiver operating characteristic curve (ROC-AUC): 0.94) for the differentiation between steatosis and hepatic inflammation, and reached almost the maximum accuracy (ROC-AUC: 0.998) upon the addition of CK-18.CONCLUSIONS:Plasma CatD holds a high diagnostic value to distinguish pediatric patients with hepatic inflammation from children with steatosis.

Original languageEnglish
Pages (from-to)462-470
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume110
Issue number3
DOIs
Publication statusPublished - Mar 10 2015

Fingerprint

Cathepsin D
Pediatrics
Inflammation
Liver
Keratin-18
D-Alanine Transaminase
ROC Curve
Area Under Curve
Biopsy
End Stage Liver Disease
Non-alcoholic Fatty Liver Disease
Fatty Liver
Alanine Transaminase
Disease Progression
Fibrosis
Peptide Hydrolases
Fats

ASJC Scopus subject areas

  • Gastroenterology
  • Medicine(all)

Cite this

Walenbergh, S. M. A., Houben, T., Hendrikx, T., Jeurissen, M. L. J., Van Gorp, P. J., Vreugdenhil, A. C. E., ... Shiri-Sverdlov, R. (2015). Plasma cathepsin D levels: A novel tool to predict pediatric hepatic inflammation. American Journal of Gastroenterology, 110(3), 462-470. https://doi.org/10.1038/ajg.2015.29

Plasma cathepsin D levels : A novel tool to predict pediatric hepatic inflammation. / Walenbergh, Sofie M A; Houben, Tom; Hendrikx, Tim; Jeurissen, Mike L J; Van Gorp, Patrick J.; Vreugdenhil, Anita C E; Adriaanse, Marlou P.; Buurman, Wim A.; Hofker, Marten H.; Mosca, Antonella; Lindsey, Patrick J.; Alisi, Anna; Liccardo, Daniela; Panera, Nadia; Koek, Ger H.; Nobili, Valerio; Shiri-Sverdlov, Ronit.

In: American Journal of Gastroenterology, Vol. 110, No. 3, 10.03.2015, p. 462-470.

Research output: Contribution to journalArticle

Walenbergh, SMA, Houben, T, Hendrikx, T, Jeurissen, MLJ, Van Gorp, PJ, Vreugdenhil, ACE, Adriaanse, MP, Buurman, WA, Hofker, MH, Mosca, A, Lindsey, PJ, Alisi, A, Liccardo, D, Panera, N, Koek, GH, Nobili, V & Shiri-Sverdlov, R 2015, 'Plasma cathepsin D levels: A novel tool to predict pediatric hepatic inflammation', American Journal of Gastroenterology, vol. 110, no. 3, pp. 462-470. https://doi.org/10.1038/ajg.2015.29
Walenbergh SMA, Houben T, Hendrikx T, Jeurissen MLJ, Van Gorp PJ, Vreugdenhil ACE et al. Plasma cathepsin D levels: A novel tool to predict pediatric hepatic inflammation. American Journal of Gastroenterology. 2015 Mar 10;110(3):462-470. https://doi.org/10.1038/ajg.2015.29
Walenbergh, Sofie M A ; Houben, Tom ; Hendrikx, Tim ; Jeurissen, Mike L J ; Van Gorp, Patrick J. ; Vreugdenhil, Anita C E ; Adriaanse, Marlou P. ; Buurman, Wim A. ; Hofker, Marten H. ; Mosca, Antonella ; Lindsey, Patrick J. ; Alisi, Anna ; Liccardo, Daniela ; Panera, Nadia ; Koek, Ger H. ; Nobili, Valerio ; Shiri-Sverdlov, Ronit. / Plasma cathepsin D levels : A novel tool to predict pediatric hepatic inflammation. In: American Journal of Gastroenterology. 2015 ; Vol. 110, No. 3. pp. 462-470.
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abstract = "OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is the most severe form of a hepatic condition known as nonalcoholic fatty liver disease (NAFLD). NASH is histologically characterized by hepatic fat accumulation, inflammation, and ballooning, and eventually coupled with fibrosis that, in turn, may progress to end-stage liver disease even in young individuals. Hence, there is a critical need for specific noninvasive markers to predict hepatic inflammation at an early age. We investigated whether plasma levels of cathepsin D (CatD), a lysosomal protease, correlated with the severity of liver inflammation in pediatric NAFLD.METHODS:Liver biopsies from children (n=96) with NAFLD were histologically evaluated according to the criteria of Kleiner (NAFLD activity score) and the Brunt's criteria. At the time of liver biopsy, blood was taken and levels of CatD, alanine aminotransferase (ALT), and cytokeratin-18 (CK-18) were measured in plasma.RESULTS:Plasma CatD levels were significantly lower in subjects with liver inflammation compared with steatotic subjects. Furthermore, we found that CatD levels were gradually reduced and corresponded with increasing severity of liver inflammation, steatosis, hepatocellular ballooning, and NAFLD activity score. CatD levels correlated with pediatric NAFLD disease progression better than ALT and CK-18. In particular, CatD showed a high diagnostic accuracy (area under receiver operating characteristic curve (ROC-AUC): 0.94) for the differentiation between steatosis and hepatic inflammation, and reached almost the maximum accuracy (ROC-AUC: 0.998) upon the addition of CK-18.CONCLUSIONS:Plasma CatD holds a high diagnostic value to distinguish pediatric patients with hepatic inflammation from children with steatosis.",
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AU - Walenbergh, Sofie M A

AU - Houben, Tom

AU - Hendrikx, Tim

AU - Jeurissen, Mike L J

AU - Van Gorp, Patrick J.

AU - Vreugdenhil, Anita C E

AU - Adriaanse, Marlou P.

AU - Buurman, Wim A.

AU - Hofker, Marten H.

AU - Mosca, Antonella

AU - Lindsey, Patrick J.

AU - Alisi, Anna

AU - Liccardo, Daniela

AU - Panera, Nadia

AU - Koek, Ger H.

AU - Nobili, Valerio

AU - Shiri-Sverdlov, Ronit

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N2 - OBJECTIVES:Nonalcoholic steatohepatitis (NASH) is the most severe form of a hepatic condition known as nonalcoholic fatty liver disease (NAFLD). NASH is histologically characterized by hepatic fat accumulation, inflammation, and ballooning, and eventually coupled with fibrosis that, in turn, may progress to end-stage liver disease even in young individuals. Hence, there is a critical need for specific noninvasive markers to predict hepatic inflammation at an early age. We investigated whether plasma levels of cathepsin D (CatD), a lysosomal protease, correlated with the severity of liver inflammation in pediatric NAFLD.METHODS:Liver biopsies from children (n=96) with NAFLD were histologically evaluated according to the criteria of Kleiner (NAFLD activity score) and the Brunt's criteria. At the time of liver biopsy, blood was taken and levels of CatD, alanine aminotransferase (ALT), and cytokeratin-18 (CK-18) were measured in plasma.RESULTS:Plasma CatD levels were significantly lower in subjects with liver inflammation compared with steatotic subjects. Furthermore, we found that CatD levels were gradually reduced and corresponded with increasing severity of liver inflammation, steatosis, hepatocellular ballooning, and NAFLD activity score. CatD levels correlated with pediatric NAFLD disease progression better than ALT and CK-18. In particular, CatD showed a high diagnostic accuracy (area under receiver operating characteristic curve (ROC-AUC): 0.94) for the differentiation between steatosis and hepatic inflammation, and reached almost the maximum accuracy (ROC-AUC: 0.998) upon the addition of CK-18.CONCLUSIONS:Plasma CatD holds a high diagnostic value to distinguish pediatric patients with hepatic inflammation from children with steatosis.

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