HCV is a complex and progressive disease in which the interaction of the host and virus has profound effects. The combination of clinical and experimental variability can seriously confound the results of a gene expression study and mandates that a large number of patients and samples be examined. The fact that liver pathology can be similar among a number of different diseases also necessitates that many different patients and diseases are included in the analysis. Accordingly, we have analyzed large numbers of patients and controls, and have maintained careful databases of clinical details in order to perform multivariate analyses of the gene array data. At present we have used a 19K human microarray to determine hepatic gene expression in 86 HCV patients and have compared these to 24 normal, 20 HBV and 14 PBC patients. The array data are of high quality: our rates of confirmation by real-time PCR exceed 80%. We have now examined the relative contributions of age, sex, viral genotype (1 vs 2/3), degree of fibrosis and disease activity on the genes most upregulated by infection with HCV.The most important determinant of consistent gene expression profiles in HCV infected livers is viral genotype (genotype 1 vs all others). However, within Genotype 1 samples there is a clear difference in gene expression.