Abstract
Non-alcoholic steatohepatitis (NASH) is associated with an increased risk of hepatocellular carcinoma (HCC). Expression levels of hepatic oncogenes, alpha-fetoprotein (afp) and osteopontin (opn)/secreted phosphoprotein 1 (spp1), were investigated using a model of diet-induced NASH. Mice were randomized to a standard diet or a fast-food diet (FFD) for 17 months. Livers from the FFD cohort exhibited hallmark characteristics of NASH with liver fibrosis, with a subset of animals exhibiting HCC. Expression levels of hepatic afp and opn/spp1 were elevated ~2.5 and ~5-fold, respectively, in the FFD cohort. Hepatic opn/spp1 exhibited a direct (r = 0.65) and significant (p < 0.01) correlation with liver hydroxyproline content. Receiver operating characteristic (ROC) curve analysis for hepatic afp, as a diagnostic for HCC, returned an area under (AU) ROC 0.84, a sensitivity of 87.5%, a specificity of 77% and a threshold of >1.05-fold change in mRNA level. The use of hepatic opn/ssp1 as a diagnostic for HCC returned an AUROC 0.88, a sensitivity of 83.3%, a specificity of 86.7% and a threshold of >2.4-fold change in mRNA level. These data point to a transformation of NASH to an oncotype with hepatic oncogene levels as a diagnostic for NASH.
Highlights
In the United States, millions of adults present with non-alcoholic fatty liver disease (NAFLD), with this number being higher worldwide [1,2]
The NAFLD continuum progresses from accumulation of lipids to non-alcoholic steatohepatitis (NASH), scarring, cirrhosis and primary liver cancer or hepatocellular carcinoma (HCC) [3,4,5]
NASH was accompanied with matrix deposition, evidenced by the
Summary
In the United States, millions of adults present with non-alcoholic fatty liver disease (NAFLD), with this number being higher worldwide [1,2]. The NAFLD continuum progresses from accumulation of lipids to non-alcoholic steatohepatitis (NASH), scarring, cirrhosis and primary liver cancer or hepatocellular carcinoma (HCC) [3,4,5]. A NASH patient, unlike a cirrhotic patient, is rarely screened for liver cancer [11,12]. This is unfortunate considering that (a) NASH is emerging as a major cause of primary liver cancer and (b) liver tissue is frequently obtained to diagnose
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