Steatosis in chronic hepatitis C: association with increased messenger RNA expression of collagen I, tumor necrosis factor-alpha and cytochrome P450 2E1.
BACKGROUND
Increased levels of tumor necrosis factor (TNF)-alpha and oxidative stress have been implicated as factors contributing to hepatic injury in fatty liver diseases. As steatosis is associated with an accelerated progression of fibrosis in chronic hepatitis C (HCV), we hypothesized that the messenger (m)RNA expression of genes involved with the production of reactive oxygen species, inflammation and cellular injury would be increased in liver tissue from subjects with steatosis and chronic HCV.


METHODS
Real-time polymerase chain reaction was performed to determine relative mRNA expression levels of collagen I, TNF-alpha, cytochrome P450 2E1 (CYP 2E1), transforming growth factor-beta1 and CD14 in liver biopsies from 38 patients with chronic HCV. The mRNA expression levels were compared between subjects with and without steatosis, fibrosis, and inflammation.


RESULTS
Multivariate analysis demonstrated that collagen I mRNA expression was increased by 199% in steatosis (P = 0.02), 85% in moderate to severe fibrosis (P = 0.02) and 157% in inflammation (P = 0.03). Livers of patients with steatosis also had an increase in TNF-alpha mRNA expression by 50% (P = 0.03) and CYP 2E1 expression by 37% (P = 0.04) compared with non-steatotic livers. Tumor necrosis factor-alpha protein was localized to Kupffer cells, bile ducts and portal inflammatory cells by immunohistochemistry.


CONCLUSIONS
Increased expression of TNF-alpha may be involved in the pathogenesis of liver injury and progression of fibrosis in individuals who have steatosis in association with chronic HCV.
Gochee
Peter A
PA
Departments of Surgery, The University of Queesland, Australia.
Jonsson
Julie R
JR
Clouston
Andrew D
AD
Pandeya
Nirmala
N
Purdie
David M
DM
Powell
Elizabeth E
EE
D000328:Adult; D000970:Antineoplastic Agents / Q000032:analysis*; D024042:Collagen Type I / Q000032:analysis* / Q000235:genetics*; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis* / Q000235:genetics*; D005234:Fatty Liver / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000235:genetics*
D000970:Antineoplastic Agents; D024042:Collagen Type I; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D019392:Cytochrome P-450 CYP2E1