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Gene expression profile associated with superimposed non‐alcoholic fatty liver disease and hepatic fibrosis in patients with chronic hepatitis C
Author(s) -
Younossi Zobair M.,
Afendy Arian,
Stepanova Maria,
Hossain Noreen,
Younossi Issah,
Ankrah Kathy,
Gramlich Terry,
Baranova Ancha
Publication year - 2009
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/j.1478-3231.2009.02060.x
Subject(s) - steatosis , hepatic fibrosis , steatohepatitis , fatty liver , fibrosis , medicine , hepatitis c virus , genotype , hepatitis c , gene expression , gastroenterology , biology , immunology , gene , disease , virus , genetics
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.