Gene expression profile associated with superimposed non-alcoholic fatty liver disease and hepatic fibrosis in patients with chronic hepatitis C
Article first published online: 9 JUN 2009
© 2009 John Wiley & Sons A/S
Volume 29, Issue 9, pages 1403–1412, October 2009
How to Cite
Younossi, Z. M., Afendy, A., Stepanova, M., Hossain, N., Younossi, I., Ankrah, K., Gramlich, T. and Baranova, A. (2009), Gene expression profile associated with superimposed non-alcoholic fatty liver disease and hepatic fibrosis in patients with chronic hepatitis C. Liver International, 29: 1403–1412. doi: 10.1111/j.1478-3231.2009.02060.x
- Issue published online: 3 SEP 2009
- Article first published online: 9 JUN 2009
- Received 23 March 2009Accepted 21 April 2009
- chronic hepatitis C infection;
- gene expression;
- genotype 3;
Background: Hepatic steatosis occurs in 40–70% of patients chronically infected with hepatitis C virus [chronic hepatitis C (CH-C)]. Hepatic steatosis in CH-C is associated with progressive liver disease and a low response rate to antiviral therapy.
Aim: Gene expression profiles were examined in CH-C patients with and without hepatic steatosis, non-alcoholic steatohepatitis (NASH) and fibrosis.
Methods: This study included 65 CH-C patients who were not receiving antiviral treatment. Total RNA was extracted from peripheral blood mononuclear cells, quantified and used for one-step reverse transcriptase-polymerase chain reaction to profile 153 mRNAs that were normalized with six ‘housekeeping’ genes and a reference RNA. Multiple regression and stepwise selection assessed differences in gene expression and the models' performances were evaluated.
Results: Models predicting the grade of hepatic steatosis in patients with CH-C genotype 3 involved two genes: SOCS1 and IFITM1, which progressively changed their expression level with the increasing grade of steatosis. On the other hand, models predicting hepatic steatosis in non-genotype 3 patients highlighted MIP-1 cytokine encoding genes: CCL3 and CCL4 as well as IFNAR and PRKRIR. Expression levels of PRKRIR and SMAD3 differentiated patients with and without superimposed NASH only in the non-genotype 3 cohort (area under the receiver operating characteristic curve=0.822, P-value 0.006]. Gene expression signatures related to hepatic fibrosis were not genotype specific.
Conclusions: Gene expression might predict moderate to severe hepatic steatosis, NASH and fibrosis in patients with CH-C, providing potential insights into the pathogenesis of hepatic steatosis and fibrosis in these patients.