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Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis

Background and Aim: To date, there are limited data on the applicability of cathepsin D for the diagnosis and monitoring of non-alcoholic steatohepatitis (NASH). Methods: This study included patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosed between November 2012 and Oct...

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Main Authors: Kamarajah, Sivesh Kathir, Khoo, Stanley, Chan, Wah Kheong, Sthaneshwar, Pavai, Nik Mustapha, Nik Raihan, Mahadeva, Sanjiv
Format: Article
Published: Wiley 2019
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R Medicine
Online Access:http://eprints.um.edu.my/24172/
https://doi.org/10.1002/jgh3.12178
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spelling my.um.eprints.241722020-04-08T05:35:30Z http://eprints.um.edu.my/24172/ Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis Kamarajah, Sivesh Kathir Khoo, Stanley Chan, Wah Kheong Sthaneshwar, Pavai Nik Mustapha, Nik Raihan Mahadeva, Sanjiv R Medicine Background and Aim: To date, there are limited data on the applicability of cathepsin D for the diagnosis and monitoring of non-alcoholic steatohepatitis (NASH). Methods: This study included patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosed between November 2012 and October 2015. Serum cathepsin D levels were measured using the CatD enzyme-linked immunosorbent assay (USCN Life Science, Wuhan, China) using stored samples collected on the same day of the liver biopsy procedure. The performance of cathepsin D in the diagnosis and monitoring of NASH was evaluated using receiver operating characteristic analysis. Results: Data for 216 liver biopsies and 34 healthy controls were analyzed. The mean cathepsin D level was not significantly different between NAFLD patients and controls; between NASH and non-NASH patients; and across the different steatosis, lobular inflammation, and hepatocyte ballooning grades. The area under receiver operating characteristic curve (AUROC) of cathepsin D for the diagnosis of NAFLD and NASH was 0.62 and 0.52, respectively. The AUROC of cathepsin D for the diagnosis of the different steatosis, lobular inflammation, and hepatocyte ballooning grades ranged from 0.51 to 0.58. Of the 216 liver biopsies, 152 were paired liver biopsies from 76 patients who had a repeat liver biopsy after 48 weeks. There was no significant change in the cathepsin D level at follow-up compared to baseline in patients who had histological improvement or worsening for steatosis, lobular inflammation, and hepatocyte ballooning grades. Cathepsin D was poor for predicting improvement or worsening of steatosis and hepatocyte ballooning, with AUROC ranging from 0.47 to 0.54. It was fair for predicting worsening (AUROC 0.73) but poor for predicting improvement (AUROC 0.54) of lobular inflammation. Conclusion: Cathepsin D was a poor biomarker for the diagnosis and monitoring of NASH in our cohort of Asian patients, somewhat inconsistent with previous observations in Caucasian patients. Further studies in different cohorts are needed to verify our observation. © 2019 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd. Wiley 2019 Article PeerReviewed Kamarajah, Sivesh Kathir and Khoo, Stanley and Chan, Wah Kheong and Sthaneshwar, Pavai and Nik Mustapha, Nik Raihan and Mahadeva, Sanjiv (2019) Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis. JGH Open, 3 (5). pp. 417-424. ISSN 2397-9070 https://doi.org/10.1002/jgh3.12178 doi:10.1002/jgh3.12178
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
spellingShingle R Medicine
Kamarajah, Sivesh Kathir
Khoo, Stanley
Chan, Wah Kheong
Sthaneshwar, Pavai
Nik Mustapha, Nik Raihan
Mahadeva, Sanjiv
Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis
description Background and Aim: To date, there are limited data on the applicability of cathepsin D for the diagnosis and monitoring of non-alcoholic steatohepatitis (NASH). Methods: This study included patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD) diagnosed between November 2012 and October 2015. Serum cathepsin D levels were measured using the CatD enzyme-linked immunosorbent assay (USCN Life Science, Wuhan, China) using stored samples collected on the same day of the liver biopsy procedure. The performance of cathepsin D in the diagnosis and monitoring of NASH was evaluated using receiver operating characteristic analysis. Results: Data for 216 liver biopsies and 34 healthy controls were analyzed. The mean cathepsin D level was not significantly different between NAFLD patients and controls; between NASH and non-NASH patients; and across the different steatosis, lobular inflammation, and hepatocyte ballooning grades. The area under receiver operating characteristic curve (AUROC) of cathepsin D for the diagnosis of NAFLD and NASH was 0.62 and 0.52, respectively. The AUROC of cathepsin D for the diagnosis of the different steatosis, lobular inflammation, and hepatocyte ballooning grades ranged from 0.51 to 0.58. Of the 216 liver biopsies, 152 were paired liver biopsies from 76 patients who had a repeat liver biopsy after 48 weeks. There was no significant change in the cathepsin D level at follow-up compared to baseline in patients who had histological improvement or worsening for steatosis, lobular inflammation, and hepatocyte ballooning grades. Cathepsin D was poor for predicting improvement or worsening of steatosis and hepatocyte ballooning, with AUROC ranging from 0.47 to 0.54. It was fair for predicting worsening (AUROC 0.73) but poor for predicting improvement (AUROC 0.54) of lobular inflammation. Conclusion: Cathepsin D was a poor biomarker for the diagnosis and monitoring of NASH in our cohort of Asian patients, somewhat inconsistent with previous observations in Caucasian patients. Further studies in different cohorts are needed to verify our observation. © 2019 The Authors. JGH Open: An open access journal of gastroenterology and hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.
format Article
author Kamarajah, Sivesh Kathir
Khoo, Stanley
Chan, Wah Kheong
Sthaneshwar, Pavai
Nik Mustapha, Nik Raihan
Mahadeva, Sanjiv
author_facet Kamarajah, Sivesh Kathir
Khoo, Stanley
Chan, Wah Kheong
Sthaneshwar, Pavai
Nik Mustapha, Nik Raihan
Mahadeva, Sanjiv
author_sort Kamarajah, Sivesh Kathir
title Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis
title_short Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis
title_full Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis
title_fullStr Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis
title_full_unstemmed Limited applicability of cathepsin D for the diagnosis and monitoring of non‐alcoholic steatohepatitis
title_sort limited applicability of cathepsin d for the diagnosis and monitoring of non‐alcoholic steatohepatitis
publisher Wiley
publishDate 2019
url http://eprints.um.edu.my/24172/
https://doi.org/10.1002/jgh3.12178
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score 13.211869

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