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arXiv · 1710.00960

A Circulating Biomarker-based Framework for Diagnosis of Hepatocellular Carcinoma in a Clinically Relevant Model of Non-alcoholic Steatohepatitis; An OAD to NASH

Ping Zhou·Anne Hwang·Christopher Shi·Edward Zhu·Farha Naaz·Zainab Rasheed·Michelle Liu·Lindsey S. Jung·Jingsong Li·Kai Jiang·Latha Paka·Michael A. Yamin·Itzhak D. Goldberg·Prakash Narayan
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Abstract

Although cirrhosis is a key risk factor for the development of hepatocellular carcinoma (HCC), mounting evidence indicates that in a subset of patients presenting with non-alcoholic steatohepatitis (NASH), HCC manifests in the absence of cirrhosis. Given the sheer size of the non-alcoholic fatty liver disease (NAFLD) epidemic, and the dismal prognosis associated with late-stage primary liver cancer, there is an urgent need for HCC surveillance in the NASH patient. In the present study, adult male mice randomized to control diet or a fast food diet (FFD) were followed for up to 14 mo and serum level of a panel of HCC-relevant biomarkers was compared with liver biopsies at 3 and 14 mo. Both NAFLD Activity Score (NAS) and hepatic hydroxyproline content were elevated at 3 and 14 mo on FFD. Picrosirius red staining of liver sections revealed a filigree pattern of fibrillar collagen deposition with no cirrhosis at 14 mo on FFD. Nevertheless, 46% of animals bore one or more tumors on their livers confirmed as HCC in hematoxylin-eosin-stained liver sections. Receiver operating characteristic (ROC) curves analysis for serum levels of the HCC biomarkers osteopontin (OPN), alpha-fetoprotein (AFP) and Dickkopf-1 (DKK1) returned concordance-statistic/area under ROC curve of > 0.89. These data suggest that serum levels of OPN (threshold, 218 ng/mL; sensitivity, 82%; specificity, 86%), AFP (136 ng/mL; 91%; 97%) and DKK1 (2.4 ng/mL; 82%; 81%) are diagnostic for HCC in a clinically relevant model of NASH

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Ping Zhou, Anne Hwang, Christopher Shi, Edward Zhu, Farha Naaz, Zainab Rasheed, Michelle Liu, Lindsey S. Jung, Jingsong Li, Kai Jiang, Latha Paka, Michael A. Yamin, Itzhak D. Goldberg, Prakash Narayan. 2017-10-03. A Circulating Biomarker-based Framework for Diagnosis of Hepatocellular Carcinoma in a Clinically Relevant Model of Non-alcoholic Steatohepatitis; An OAD to NASH. https://arxiv.org/abs/1710.00960

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