Gene expression profile associated with superimposed non-alcoholic fatty liver disease and hepatic fibrosis in patients with chronic hepatitis C.
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.


OBJECTIVE
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.
Younossi
Zobair M
ZM
Center for Liver Diseases at Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA 22042, USA. zobair.younossi@inova.org
Afendy
Arian
A
Stepanova
Maria
M
Hossain
Noreen
N
Younossi
Issah
I
Ankrah
Kathy
K
Gramlich
Terry
T
Baranova
Ancha
A
D000328:Adult; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000145:classification; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged