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AIM: To search for transcription dysregulation that could (1) differentiate hepatocellular carcinoma (HCC)-free from HCC-related cirrhosis (2) differentiate HCCfree cirrhosis related to HCV from that related to alcohol intake.METHODS: Using microarray analysis, we compared transcript levels in HCC-free cirrhosis (alcoholism: 7;hepatitis C: 7), HCC-associated cirrhosis (alcoholism:10; hepatitis C: 10) and eight control livers. The identified transcripts were validated by qRT-PCR in an independent cohort of 45 samples (20 HCCfree cirrhosis; 15 HCC-associated cirrhosis and 10 control livers). We also confirmed our results by immunohistochemistry.transcripts which differentiated between alcoholicrelated cirrhosis, HCV-related cirrhosis and control livers. They mainly corresponded to down-regulation.Dysregulation of Signal Transduction and Activator of Transcription-3 (STAT-3) was found along with related changes in STAT-3 targets which occurred in an etiology-dependent fashion in HCC-free cirrhosis.In contrast, in HCC, such transcription dysregulations were not observed.CONCLUSION: We report that transcriptional dysregulations exist in HCC-free cirrhosis, are transiently observed prior to detectable HCC onset and may be appear like markers from cirrhosis to HCC transition.