Introduction Although genotype (G)3 HCV is generally regarded as “easy to treat”, based on clinical trial data showing response rates of up to 80%, real world studies have shown substantially lower rates of treatment response (45%), particularly in patients with advanced fibrosis or cirrhosis. Most patients who fail treatment for G3 HCV initially respond to antiviral therapy, but relapse after the end of treatment. HCV RNA has been demonstrated in peripheral blood mononuclear cells from patients with chronic HCV, but whether viral replication occurs in these cells remains controversial. This study tests the hypothesis that viable HCV in monocytes at the end of treatment predicts relapse in patients with G3 HCV.
Methods CD14 (+) monocytes from patients at the end of treatment for G3 HCV were isolated and fused with HuH7 cells. The fused cells were maintained in tissue culture for up to 5 days, before extraction of HCV RNA and quantification by PCR. p Values were derived using the Mann–Whitney U test for comparison of non-parametric data. Results are expressed as mean ± SEM.
Results HCV RNA increased up to fivefold in fused compared to unfused monocytes. Viral protein production was demonstrated in fused cells by indirect immunofluorescence, confirming that viral replication occurs in the fused cells. Fused monocytes from patients who relapsed after treatment showed a significantly greater increase in HCV RNA than those from patients with a sustained virological response (246.8±103.9%, compared to 5±33.9%, p=0.02).
Conclusion These data demonstrate that the presence of replication-competent HCV in monocytes at the end of treatment predicts relapse in patients with G3 HCV. Monocytes may act as a sanctuary site for HCV virions during interferon-based treatment, facilitating relapse after withdrawal of therapy.
Competing interests M Cunningham: None declared, A Javaid: None declared, J Waters: None declared, G Foster Grant/Research Support from: Roche, Janssen, Tibotec, Novartis, Consultant for: Abbott, BI, BMS, Chughai, Janssen, Merck, Novartis, Roche, Tibotec.
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