Liver Lipids of Patients with Hepatitis B and C and Associated Hepatocellular Carcinoma.

Elisabeth M Haberl,Sabrina Krautbauer,Christa Buechler,Jürgen J Wenzel,Thomas S Weiss,Josch K Pauling,Marcus Höring,Gerhard Liebisch,Georg Peschel,Nikolai Köhler,Kilian Weigand

doi:10.3390/ijms22105297

Abstract

Hepatocellular carcinoma (HCC) still remains a difficult to cure malignancy. In recent years, the focus has shifted to lipid metabolism for the treatment of HCC. Very little is known about hepatitis B virus (HBV) and C virus (HCV)-related hepatic lipid disturbances in non-malignant and cancer tissues. The present study showed that triacylglycerol and cholesterol concentrations were similar in tumor adjacent HBV and HCV liver, and were not induced in the HCC tissues. Higher levels of free cholesterol, polyunsaturated phospholipids and diacylglycerol species were noted in non-tumorous HBV compared to HCV liver. Moreover, polyunsaturated phospholipids and diacylglycerols, and ceramides declined in tumors of HBV infected patients. All of these lipids remained unchanged in HCV-related HCC. In HCV tumors, polyunsaturated phosphatidylinositol levels were even induced. There were no associations of these lipid classes in non-tumor tissues with hepatic inflammation and fibrosis scores. Moreover, these lipids did not correlate with tumor grade or T-stage in HCC tissues. Lipid reprogramming of the three analysed HBV/HCV related tumors mostly resembled HBV-HCC. Indeed, lipid composition of non-tumorous HCV tissue, HCV tumors, HBV tumors and HBV/HCV tumors was highly similar. The tumor suppressor protein p53 regulates lipid metabolism. The p53 and p53S392 protein levels were induced in the tumors of HBV, HCV and double infected patients, and this was significant in HBV infection. Negative correlation of tumor p53 protein with free cholesterol indicates a role of p53 in cholesterol metabolism. In summary, the current study suggests that therapeutic strategies to target lipid metabolism in chronic viral hepatitis and associated cancers have to consider disease etiology.

Highlights

Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are leading causes for the pathogenesis of hepatocellular carcinoma (HCC), and are responsible for 60% to 85% of worldwide Hepatocellular carcinoma (HCC) cases [1]
Lipidomic Analysis of Tumor and Adjacent Tissues of Patients with Chronic HBV and Lipidomic profiling was conducted in tumor and adjacent tissues of 10 HBV, 11
PU phospholipids were already low in non-tumor tissues of HCV-infected patients, and a further decrease in the tumors was not observed

Summary

Introduction

Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are leading causes for the pathogenesis of hepatocellular carcinoma (HCC), and are responsible for 60% to 85% of worldwide HCC cases [1]. Patients with chronic viral infections have a high probability to develop liver cirrhosis which is a relevant risk factor for carcinogenesis regardless of disease etiology [1]. Common molecular pathways contribute to HCC development in HBV- and HCV-infected patients [2]. In HBV/HCV co-infected patients HCC is more frequent [3], suggesting that functionally distinct signaling molecules are involved in HBV- and HCV-associated tumorigenesis [2]. The liver is the central organ in lipid metabolism, and subsequently, systemic lipoproteins were low in patients with liver cirrhosis [4]. Lipoproteins are particles composed of multiple lipid classes and serum cholesterol and sphingolipid levels declined in parallel with liver function [4]

Methods

Results

Conclusion