TT virus infection in patients with chronic hepatitis C virus infection - effect of primers, prevalence, and clinical significance

Background/Aim: A novel DNA virus, TT virus (TTV), was recently identified in patients with posttransfusion non-A-G hepatitis. The aim of this study was to determine the prevalence and clinical significance of TTV infection in patients with chronic hepatitis C virus (HCV) infection. Methods: We analyzed pretreatment serum samples from 171 United States and European patients who relapsed after interferon-α treatment and were recruited into an interferon-α-2b/ribavirin combination treatment trial. TTV DNA was detected by PCR using two different set of primers (TTV-A and TTV-B) derived from open reading frames 1 and 2, respectively. Results: TTV was detected in 29.2% of the patients with the TTV-A primer set, 70.8% with the TTV-B primer-set, and 72.5% if positive by either/both sets of the primers. The amplicons generated by primer set A were sequenced and a phylogenetic tree was constructed. The 50 isolates belonged to group 1a (n=8), 1b (n=17), 2a (n=21), 2b (n=3), and 4 (n=1). There was no difference in demographic (age, sex distribution, estimated duration of HCV infection), biochemical (serum ALT levels), virologic (serum HCV RNA levels, HCV genotype distribution), or histologic scores, and their subsequent response to either interferon-α-2b or interferon-α-2b/ribavirin combination treatment. Conclusions: The prevalence of TTV infection reported previously may have been significantly underestimated, based on the primers originally described and used by most studies. Although TTV infection is very common in patients with chronic HCV infection, it has no identifiable clinical significance.