BACKGROUND/AIMS: Although hepatitis C virus (HCV) is considered essentially hepatotropic, recent studies suggest that it can also infect peripheral blood mononuclear cells (PBMC). Interferon (IFN) seems to suppress hepatic virus expression, so the continued presence of the virus in PBMC might explain why interferon often fails to induce a long-term response. We investigated whether clearance of plasma viraemia after IFN treatment was associated with clearance of viral RNA from PBMC. METHODOLOGY: Fifty patients with histologically proven chronic hepatitis C were treated with IFN plus ribavirin for 48 weeks; they all achieved clearance of HCV RNA from serum. Six months later, PBMC and serum were examined by real-time polymerase chain reaction (PCR). Patients with undetectable plasma HCV RNA after the six-month follow-up were classified as sustained responders (SR), patients who cleared the virus from their serum but with HCV RNA reappearance during follow-up were classified as relapse responders (RR). RESULTS: Twenty six percent of the SVR patients had detectable level of HCV RNA in PBMC. All of RR patients had detectable HCV RNA in PBMC. Concerning the comparison of HCV RNA quantization in serum and PBMC at the end of therapy there was a strong correlation between HCV RNA level in serum and PBMC. Comparing the previous histopathological results with HCV RNA levels in serum and PBMC, there was a significant elevation of both serum and PBMC HCV RNA levels in patients with histological activity index (HAI) Grade 3 compared to those in serum and PBMC of patients with HAI grade 1. CONCLUSION: PBMC infected with HCV can serve as a virus reservoir. In addition, lack of detection of viraemia at the end of treatment alone does not indicate absence of circulating virus and patients are likely to be at great risk of hepatitis C recurrence.
BACKGROUND/AIMS: Although hepatitis C virus (HCV) is considered essentially hepatotropic, recent studies suggest that it can also infect peripheral blood mononuclear cells (PBMC). Interferon (IFN) seems to suppress hepatic virus expression, so the continued presence of the virus in PBMC might explain why interferon often fails to induce a long-term response. We investigated whether clearance of plasma viraemia after IFN treatment was associated with clearance of viral RNA from PBMC. METHODOLOGY: Fifty patients with histologically proven chronic hepatitis C were treated with IFN plus ribavirin for 48 weeks; they all achieved clearance of HCV RNA from serum. Six months later, PBMC and serum were examined by real-time polymerase chain reaction (PCR). Patients with undetectable plasma HCV RNA after the six-month follow-up were classified as sustained responders (SR), patients who cleared the virus from their serum but with HCV RNA reappearance during follow-up were classified as relapse responders (RR). RESULTS: Twenty six percent of the SVR patients had detectable level of HCV RNA in PBMC. All of RR patients had detectable HCV RNA in PBMC. Concerning the comparison of HCV RNA quantization in serum and PBMC at the end of therapy there was a strong correlation between HCV RNA level in serum and PBMC. Comparing the previous histopathological results with HCV RNA levels in serum and PBMC, there was a significant elevation of both serum and PBMC HCV RNA levels in patients with histological activity index (HAI) Grade 3 compared to those in serum and PBMC of patients with HAI grade 1. CONCLUSION: PBMC infected with HCV can serve as a virus reservoir. In addition, lack of detection of viraemia at the end of treatment alone does not indicate absence of circulating virus and patients are likely to be at great risk of hepatitis C recurrence.