Evidence of aberrant lipid metabolism in hepatitis C and hepatocellular carcinoma.
OBJECTIVE
Lipids are linked to many pathological processes including hepatic steatosis and liver malignancy. This study aimed to explore lipid metabolism in hepatitis C virus (HCV) and HCV-related hepatocellular carcinoma (HCC).


METHODS
Serum lipids were measured in normal, HCV and HCV-HCC patients. Whole-genome microarray was performed to identify potential signature genes involved in lipid metabolism characterizing normal vs. HCV vs. HCV-HCC conditions.


RESULTS
Serum cholesterol was significantly reduced in HCV and HCV-HCC patients compared with normal controls, whereas there was no difference in glucose and triglycerides. Microarray analysis identified 224 probe sets with known functional roles in lipid metabolism (anova, 1.5-fold, P ≤ 0.001). Gene-mediated fatty acid (FA) de novo synthesis and uptake were upregulated in HCV and this upregulation was further enhanced in HCC. Genes involved in FA oxidation were downregulated in both the HCV and HCC groups. The abnormality of cholesterol metabolism in HCV was associated with downregulation of genes involved in cholesterol biosynthesis, absorption and transportation and bile acid synthesis; this abnormality was further intensified in HCC.


CONCLUSIONS
Our data support the notion that HCV-related lipid metabolic abnormalities may contribute to hepatic steatosis and the development of cancer. Identification of these aberrations would stratify patients and improve treatment algorithms.
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA. jw17@iupui.edu
Jian-Min
JM
Wu
Nicholas J
NJ
Skill
Mary A
MA
Maluccio
D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D002784:Cholesterol / Q000097:blood; D016000:Cluster Analysis; D005227:Fatty Acids / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D006526:Hepatitis C / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007196:Indiana; D050356:Lipid Metabolism / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D005227:Fatty Acids; D014280:Triglycerides; D002784:Cholesterol