TT Virus Viremia and Liver Transplantation: No Significant Increase of the Prevalence

To the Editor:

TT virus (TTV) is a novel DNA virus that has been assumed to be associated with posttransfusion hepatitis.1,2 A recent investigation showed that, in 28 of 200 healthy blood donors (14%), TTV viremia could be detected by polymerase chain reaction (PCR).3 To determine the risk for TTV transmission by blood and blood products, we examined 104 patients (39 women and 65 men; mean age, 49 years) who underwent liver transplantation (LTX) between 1992 and 1996 in a retrospective study. These patients are at high risk for acquiring transfusion transmitted agents due to the numerous units of blood and blood products administered during surgery. Seventeen of them (16.4%) had a history of fulminant hepatic failure (FHF) that was due to hepatitis B virus (HBV; n = 5), to hepatitis A virus (HAV; n = 1), or of unknown etiology (n = 11). The other 87 patients (83.7%) had liver cirrhosis due to autoimmune hepatitis (n = 24), chronic hepatitis C virus (HCV) infection (n = 27), chronic HBV infection (n = 11), HBV and hepatitis D virus (HDV) infection (n = 4), alcohol abuse (n = 15), or unknown etiology (n = 6).

TTV infection was investigated by nested polymerase chain reaction (PCR) using primers of a conserved region within the postulated open reading frame 1.2 Before liver transplantation, TTV DNA was detectable in 18 (17.3%) of the 104 patients. The titers of TTV viremia were determined by serial dilution and the median value was 2 × 10⁴ copies/mL. Of these 18 patients, 5 had autoimmune hepatitis, 4 were infected with HBV, 1 was infected with HBV and HDV, 5 were infected with HCV, and 1 was an alcoholic. Two of the TTV PCR-positive patients had FHF of unknown etiology. However, in the remaining 9 patients with FHF of unknown etiology, no TTV viremia was detectable. Postoperatively, the 18 initially and 7 additionally TTV viremic patients had detectable viremia in sera drawn between days 6 and 14 after transplantation. On follow-up, 5 viremic patients showed a persistent viremia for at least 18 months.

Because transfusion of blood and blood products is supposed to be a major route of TTV transmission,1 4 we examined the number of blood products (blood plasma and erythrocyte and thrombocyte concentrates) administered to the patients in connection with the LTX. There was no significant difference between the number of blood products administered to the patients who became TTV PCR-positive postoperatively (median, 108 U) and the patients who remained TTV PCR-negative (median, 140 U).

Although each patient had received a great number of blood products, our data demonstrate that the prevalence of TTV viremia did not significantly increase from 17.3% to 24% during LTX. This finding is in sharp contrast to GBV-C/HGV, where in the identical collective of patients an increase of the prevalence from 6% before to 41% after transplantation was observed, as recently described.5 The prevalence of TTV viremia in healthy blood donors was shown to vary from 1.5% to 14%.2-4 Thus, each patient must have received 2 to 20 TTV-positive units of blood products. One reason for the unexpected low increase of TTV prevalence in the recipients might be due to the presence of protective antibodies in the majority of the patients. This will be clarified as soon as serological assays for the detection of TTV antibodies are available. Furthermore, we conclude from our data that TTV infection is not linked to fulminant hepatic failure, because the prevalence in this group of patients does not exceed the prevalence in German and Japanese blood donors.2 3 Clinical studies are currently in progress to evaluate the clinical impact of TTV infection in liver transplant recipients.