Torque teno virus in liver diseases and after liver transplantation

Table 1 Torque teno virus in the context of liver transplantation: Major key points

Population, n	TTV prevalence	Study key points	Ref.
German, adult, 104	17.3% pre-LT; 24% post-LT	TTV DNA prevalence not associated with the number of transfused blood products	Schroter et al[36], 1998
British, adult, 37	16% pre-LT; 46% post-LT	prevalence and TTV viral load increased after LT; no correlation of TTV viral load with liver enzyme levels	Shang et al[39], 2000
Italian, adult, 25	100% pre-LT	TTV viral load increased significantly after LT (P < 0.001); TTV viral load was higher in patients on CNI + AZA/MMF vs CNI alone (P = 0.04) at 3 mo after LT; no differences in viral load in regard to the etiology of liver disease; no correlation of viral load and TTV genotype with ALT or histological liver damage	Burra et al[37], 2008
Canadian, pediatric, 80	68% healthy control; 71% pre-LT; 98%-99% post-LT	TTV viral load post-LT was higher than in pre-LT (P < 0.001) and healthy controls (P < 0.0001); TTV viral load was lower in post-LT chronic hepatitis; TTV viral load decreased during the post-LT follow-up; no correlation between TTV viral load and ALT or number of transfusions; TTV viral load was lower in anti-HEV IgM/IgG positive patients	Béland et al[28], 2014
Italian, adult, 46	100% pre-LT	TTV viral load increased after LT; low CNI + ECP protocol was associated with the lowest increase in TTV viral load compared to CNI only protocol (P < 0.01) or CNI + AZA/MMF protocol (P < 0.01)	Focosi et al[26], 2014
Swiss, adult, 39	74% pre-LT	TTV viral load increased significantly 6 mo post-LT vs pre-LT (P < 0.0001) and decreased 12 mo post-LT vs 6 mo post-LT; 1-yr cumulative incidence of rejection was lower (21%) in TTV positive vs 70% in TTV negative patients (P = 0.0042)	Simonetta et al[37], 2017
German, adult, 136	84.6% post-LT (serum); 66.6% post-LT (urine)	TTV viral load negatively correlated with the BKV viral load (P = 0.038), but had no impact on renal impairment	Herrmann et al[1], 2018
Italian, adult, 134	92% pre-LT	TTV viral load progressively increased to a maximum at day 80 post-LT; TTV viral load was higher on Cyc vs on Tac (P = 0.016); TTV viral load did differ between different Tac levels (within or beyond the therapeutic range); TTV viral load was lower in CMV DNA negative vs positive patients (P = 0.001); TTV viral load at day 0-10 post-LT predicts CMV reactivation (OR: 1.5, 95%CI: 1.0-2.3)	Maggi et al[30], 2018
Spanish, adult, 63	93.7% pre-LT; 100% post-LT	TTV viral load progressively increased peaking at month 3 and then decreased during months 6-12 post-LT; patients on triple IS had higher viremia vs on double IS (P < 0.001); no differences in TTV viremia according to the type of CNI; TTV viral load was lower during ACR (4.41 vs 5.95 log10 copies/mL; P = 0.002) and higher during CMV infections (5.79 vs 6.59 log10 copies/mL; P = 0.009); the area under the ROC curve of TTV viral load for moderate ACR was 0.869, with a sensitivity and negative predictive value of 100%, respectively, for a cut-off point of 4.75 log10 copies/mL; TTV viral load did not differ in long-term or tolerant patients and healthy controls	Ruiz et al[3], 2019
German, immunosuppressed patients with HBV reactivation, 87 (20 LT recipients)		TTV viral load did not differ between patients with ALF vs non-ALF; no differences in TTV viral loads diagnosed during vs after IS (P = 0.740), nor after HBV resolution vs chronic HBV (P = 0.727)	Anastasiou et al[40], 2019

ACR: Acute cellular rejection; ALF: Acute liver failure; ALT: Alanine aminotransferase; AZA: Azathioprine; BKV: BK virus; CI; Confidence interval; CMV: Cytomegalovirus; CNI: Calcineurin inhibitor; Cyc: Cyclosporine; DNA: Deoxyribonucleic acid; ECP: Extracorporeal photopheresis; HBV: Hepatitis B virus; Ig: Immunoglobulin; IS: Immunosuppression; LT: Liver transplant; MMF: Mycophenolate-mofetil; OR: Odds ratio; Tac: Tacrolimus; TTV: Torque teno virus.