Figure 6. Clinical biopsy and serum samples validate experimental model results.

(a) Log-scale scatter plot of whole-genome gene expression correlating in vitro expression levels with expression in biopsy samples from healthy liver. R² was 0.85, compared with 0.72 for HepG2 cells. (b) Log-scale scatter plot of virus-induced gene expression in vitro (culture) versus in vivo (biopsy). Changes in the expression of genes related to metabolism showed a positive (P < 0.05) correlation between in vivo and in vitro samples. 88% of the metabolic genes upregulated in vitro (red squares) were also upregulated in vivo, but downregulated genes (blue diamonds) appeared to have randomly distributed in vivo expression. (c) Metabolic analysis of infected serum samples versus controls. The results confirm previous reports that HCV induces hyperglycemia and hypolipidemia, but they also show a decrease in bile acids and a corresponding increase in ketone bodies and lactate as predicted by the in vitro model. (d) Unbiased transcriptional regulatory analysis of patient biopsy samples showed activation of key nuclear receptors, mirroring those identified in vitro.