TT virus infection in cases of fulminant hepatic failure - evaluation by clonality based on amino acid sequence of hypervariable regions

The significance of TT virus (TTV) infection in the pathogenesis of acute l iver disease is uncertain. Serum TTV-DNA was determined by polymarase-chain reaction (PCR) methods using both hemi-nested (NG059/NG063 and NG061/NG063 ) and single-step (T801/T935) primers in four patients with fulminant hepat ic failure and one patient with late onset hepatic failure in whom hepatiti s A virus (HAV) and hepatitis B virus (HBV) markers were negative. Of these five patients, the TTV-DNA was positive in two patients with fulminant hep atic failure by both PCRs before receiving blood transfusion and/or blood-p roducts infusion. Therapies including plasma exchange with blood hemodiafil tration was performed in both patients, and one survived. The non-survivor was an 18-year-old woman with TTV genotype 2 infection. In this patient, th e TTV-DNA by PCRs with both primers was positive transiently when serum ALT levels were elevated. The survivor was a 78-year-old woman with infections of TTV genotype 1b and hepatitis C virus (HCV), in whom serum ALT levels r eturned to normal at 3 weeks after the start of the therapies, but fluctuat ed after 10 weeks. TTV-DNA measured by hemi-nested primers and HCV-RNA were negative when serum ALT levels decreased, but became positive later. Semi- quantitative PCR using single-step primers revealed that serum TTV-DNA leve ls changed in correlation with both serum ALT and HCV-RNA levels. Amino aci d sequences of hypervariable regions were identical in six out of nine clon es isolated from the sera before the therapies and sequence divergence was minimal even in the other three clones, suggesting that TTV proliferated wi th clonality in the process of fulminant hepatic failure. We conclude that clonally proliferating TTV may contribute to fulminant hepatic failure as a solitary infectious agent or a co-infectious agent with HCV. (C) 2001 Else vier Science B.V. All rights reserved.