Lymphomagenesis-related gene expression in B cells from sustained virological responders with occult hepatitis C virus infection

Summary The expression of activation‐induced cytidine deaminase, B‐aggressive lymphoma, cyclin D1 and serine/threonine kinase 15 genes, among others, is increased in B cells from patients with chronic hepatitis C virus (HCV) infection. It is unknown whether the level of expression of these genes in B cells is increased in patients with hepatitis C who have achieved a sustained virological response (SVR) but who have persistent, detectable HCV RNA, so‐called occult infection. Eighty‐three patients who achieved and SVR, 27 with detectable HCV and 56 without detectable HCV RNA, 28 chronic hepatitis C patients and 32 healthy controls were studied. RNA was extracted from B cells, and gene expression levels were measured by RT‐PCR. Patients with chronic HCV and those who achieved an SVR (with and without persistent low‐level HCV RNA) showed a statistically significant higher expression compared to healthy controls, of activation‐induced cytidine deaminase (P = 0.004, P < 0.001 and P = 0.002, respectively), B‐aggressive lymphoma (P < 0.001, P = 0.001 and P = 0.006) and cyclin D1 (P = 0.026, P = 0.001; P = 0.038). For activation‐induced cytidine deaminase patients with an SVR and ‘occult infection’ had a statistically significantly higher expression level than patients with and SVR without ‘occult infection’ (P = 0.014). The higher expression levels found for activation‐induced cytidine deaminase, together with other genes indicates that these B lymphomagenesis‐related genes are upregulated following HCV therapy and this is more marked when HCV can be detected in PBMCs.