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Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis

There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline conte...

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Autores principales: Bissoondial, Tyler L., Han, Yiguang, Mullan, Stephanie, Pabla, Amrit K., Spahn, Kiera, Shi, Steven, Zheng, Lana, Zhou, Ping, Jiang, Kai, Prakash, Natalia, Bhutkar, Shraddha, Ali, Quaisar, Li, Jingsong, Hu, Zhijian, Pellicano, Anthony J., Goldberg, Itzhak D., Narayan, Prakash
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601536/
https://www.ncbi.nlm.nih.gov/pubmed/33020436
http://dx.doi.org/10.3390/diagnostics10100784
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author Bissoondial, Tyler L.
Han, Yiguang
Mullan, Stephanie
Pabla, Amrit K.
Spahn, Kiera
Shi, Steven
Zheng, Lana
Zhou, Ping
Jiang, Kai
Prakash, Natalia
Bhutkar, Shraddha
Ali, Quaisar
Li, Jingsong
Hu, Zhijian
Pellicano, Anthony J.
Goldberg, Itzhak D.
Narayan, Prakash
author_facet Bissoondial, Tyler L.
Han, Yiguang
Mullan, Stephanie
Pabla, Amrit K.
Spahn, Kiera
Shi, Steven
Zheng, Lana
Zhou, Ping
Jiang, Kai
Prakash, Natalia
Bhutkar, Shraddha
Ali, Quaisar
Li, Jingsong
Hu, Zhijian
Pellicano, Anthony J.
Goldberg, Itzhak D.
Narayan, Prakash
author_sort Bissoondial, Tyler L.
collection PubMed
description There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate.
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spelling pubmed-76015362020-11-01 Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis Bissoondial, Tyler L. Han, Yiguang Mullan, Stephanie Pabla, Amrit K. Spahn, Kiera Shi, Steven Zheng, Lana Zhou, Ping Jiang, Kai Prakash, Natalia Bhutkar, Shraddha Ali, Quaisar Li, Jingsong Hu, Zhijian Pellicano, Anthony J. Goldberg, Itzhak D. Narayan, Prakash Diagnostics (Basel) Article There is increasing evidence that nonalcoholic steatohepatitis (NASH) is a risk factor for hepatocellular carcinoma (HCC) in the absence of cirrhosis, a phenomenon termed noncirrhotic HCC. Early diagnosis of HCC is critical to a favorable prognosis. We tested the hypothesis that hydroxyproline content of liver biopsy samples is diagnostic for HCC in murine models of NASH induced by diet or by diet and chemicals. The training set comprised mice fed a standard diet or a fast-food diet with or without administration of thioacetamide. At harvest, livers from the modified diet cohort exhibited NASH with a subset of NASH livers exhibiting HCC. Hydroxyproline content was measured in liver biopsy samples with tissue in the NASH+HCC cohort sampled from the remote, nontumor parenchyma. Plotting the receiver operating characteristics (ROC) with hydroxyproline as the continuous variable against the absence or presence of HCC yielded an area under ROC of 0.87, a threshold of >0.18 μg hydroxyproline/mg liver and sensitivity of 91% with a specificity of 83.3%. The use of liver hydroxyproline content as a diagnostic for HCC in a test set comprising healthy, NASH and NASH+HCC livers proved 87% accurate. MDPI 2020-10-04 /pmc/articles/PMC7601536/ /pubmed/33020436 http://dx.doi.org/10.3390/diagnostics10100784 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bissoondial, Tyler L.
Han, Yiguang
Mullan, Stephanie
Pabla, Amrit K.
Spahn, Kiera
Shi, Steven
Zheng, Lana
Zhou, Ping
Jiang, Kai
Prakash, Natalia
Bhutkar, Shraddha
Ali, Quaisar
Li, Jingsong
Hu, Zhijian
Pellicano, Anthony J.
Goldberg, Itzhak D.
Narayan, Prakash
Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
title Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
title_full Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
title_fullStr Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
title_full_unstemmed Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
title_short Liver Biopsy Hydroxyproline Content Is a Diagnostic for Hepatocellular Carcinoma in Murine Models of Nonalcoholic Steatohepatitis
title_sort liver biopsy hydroxyproline content is a diagnostic for hepatocellular carcinoma in murine models of nonalcoholic steatohepatitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601536/
https://www.ncbi.nlm.nih.gov/pubmed/33020436
http://dx.doi.org/10.3390/diagnostics10100784
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