Distinct cellular responses differentiating alcohol- and hepatitis C virus-induced liver cirrhosis.
BACKGROUND
Little is known at the molecular level concerning the differences and/or similarities between alcohol and hepatitis C virus induced liver disease. Global transcriptional profiling using oligonucleotide microarrays was therefore performed on liver biopsies from patients with cirrhosis caused by either chronic alcohol consumption or chronic hepatitis C virus (HCV).


RESULTS
Global gene expression patterns varied significantly depending upon etiology of liver disease, with a greater number of differentially regulated genes seen in HCV-infected patients. Many of the gene expression changes specifically observed in HCV-infected cirrhotic livers were expectedly associated with activation of the innate antiviral immune response. We also compared severity (CTP class) of cirrhosis for each etiology and identified gene expression patterns that differentiated ethanol-induced cirrhosis by class. CTP class A ethanol-cirrhotic livers showed unique expression patterns for genes implicated in the inflammatory response, including those related to macrophage activation and migration, as well as lipid metabolism and oxidative stress genes.


CONCLUSIONS
Stages of liver cirrhosis could be differentiated based on gene expression patterns in ethanol-induced, but not HCV-induced, disease. In addition to genes specifically regulating the innate antiviral immune response, mechanisms responsible for differentiating chronic liver damage due to HCV or ethanol may be closely related to regulation of lipid metabolism and to effects of macrophage activation on deposition of extracellular matrix components.
Lederer
Sharon L
SL
Department of Microbiology, University of Washington, Seattle, WA, USA. leders@u.washington.edu
Walters
Kathie-Anne
KA
Proll
Sean
S
Paeper
Bryan
B
Robinzon
Shahar
S
Boix
Loreto
L
Fausto
Nelson
N
Bruix
Jordi
J
Katze
Michael G
MG
D016207:Cytokines / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006526:Hepatitis C / Q000150:complications* / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D008099:Liver / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000145:classification / Q000209:etiology* / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000145:classification / Q000209:etiology* / Q000378:metabolism
D016207:Cytokines