The platelet count increases after a sustained response to interferon (IFN) treatment for chronic hepatitis C (CH-C). However, the extent of the increase differs by patient. We investigated whether concurrent TT virus (TTV) infection interferes with the improvement of thrombocytopenia. Serial serum samples were obtained from 85 noncirrhotic CH-C patients who achieved a sustained virologic response for hepatitis C virus (HCV) upon IFN treatment, and tested for TTV DNA by three polymerase chain reaction (PCR) methods (UTR, N22 and TTV genotype-1). UTR PCR can detect essentially all TTV genotypes, whereas N22 PCR primarily detects four major TTV genotypes (1-4). Eighty-four patients (84/85, 99%) were positive for TTV DNA by UTR PCR, 27 (32%) by N22 PCR and 18 (21%) by TTV genotype-1 PCR just before IFN treatment was started (baseline). A sustained virologic response for TTV was observed in 6% (5/84) by UTR PCR, 52% (14/27) by N22 PCR and 56% (10/18) by TTV genotype-1 PCR. The platelet count was significantly lower in the N22 PCR-positive group than in the N22 PCR-negative group not only at baseline (14.9+/-3.8 vs. 18.1+/-6.4x10(4)/&mgr;l, P<0.05), but also at the non-HCV-viremic state one year after the completion of IFN treatment (15.5+/-2.8 vs. 18.6+/-5.5x10(4)/&mgr;l, P<0.05), the differences also being statistically significant by TTV genotype-1 PCR, but not by UTR PCR. These results suggest that certain TTV genotypes including genotype 1 may play a role in aggravating the thrombocytopenia of CH-C patients, either alone or in concert with HCV.