Table 7.
Effects of mTOR inhibitors on hepatitis C virus and fibrosis progression in hepatitis C virus liver transplant recipients.
| Patient survival | Graft survival | Fibrosis | HCV recurrence rate | Other | |
|---|---|---|---|---|---|
| Sirolimus | |||||
|
| |||||
| Maintenance dosing | |||||
| Wagner et al. Int Immunopharmacol. 2010; 10: 990–3 [58] | 95% survival in whole group; lower survival in SRL versus CNI according to log rank test (P < 0.03) | Viral load (×106): 6.9 versus 21.3 (SRL versus CNI, P < 0.001) | |||
|
| |||||
| De novo dosing | |||||
| McKenna et al. Am J Transplant. 2011; 11: 2379–87 [57] | 1 year after transplant: patient survival: 92.5% versus 87.9% (SRL versus control, P = 0.15) 5 years after transplant: similar patient and graft survival (Kaplan–Meier analysis) |
Fibrosis state ≥2, 1 year after transplant: 15.3% versus 36.2% (SRL versus control, P < 0.0001) 2 years after transplant: 30.1% versus 50.5% (SRL versus control, P = 0.001) |
Mean HCV RNA, 1 year after transplant: 9.16 × 106 versus 6.90 × 106 (SRL versus control, P = NS) 2 years: 6.12 × 106 versus 4.83 × 106 (P = NS) |
||
| Asthana et al. Can J Gastroenterol. 2011; 25: 28–34 [56] | Change in mean fibrosis score: +1.1 versus −0.52 (CNI versus SRL, P = 0.002) Change in mean activity: +0.24 versus −0.25 (CNI versus SRL, P = 0.056) |
HCV recurrence: 75% versus 69.8% (SRL versus controls, P = NS) | |||
| Asthana et al. Presented at AASLD 2011 (Abstract 184) [60] | SVR: 60%, 43%, 29% (SRL versus TAC versus CsA) SRL-based immunosuppression impacted SVR (OR 2.41, 95% CI 1.1, 5.5) |
||||
|
| |||||
| Late conversion (>3 months after transplantation) | |||||
| Stein et al. Presented at the American Transplant Congress 2011 (Abstract 817) [79] | 1-, 3- and 5-year allograft survival probability (%): 100, 92, 78 (SRL) and 100, 95, 90 (TAC), log rank −0.6, respectively | 1- and 3-year fibrosis and activity scores: P = NS (SRL versus TAC) | |||
|
| |||||
| Everolimus | |||||
|
| |||||
| De novo dosing | |||||
| Dopazo et al. Presented at ILTS; 2011 (Abstract P-460) [102] | Fibrosis stages I and II–IV, respectively: 8% and 30% (EVR), and 5% and 36% (control group) (P = NS) | ||||
|
| |||||
| Maintenance dosing | |||||
| Grazi et al. Presented at ILTS; 2011 (Abstract P-256) [88] | HCV recurrence rate: 54% versus 33% (EVR versus TAC, P = NS) | ||||
|
| |||||
| Early conversion (≤3 months after transplantation) | |||||
| Masetti et al. Am J Transplant. 2010; 10: 2252–62 [89] | HCV recurrence rate: 65% versus 75% (EVR versus CsA, P = 1) | ||||
P values are included where available.
AASLD: The Liver Meeting 62nd Annual Meeting of the American Association for the Study of Liver Diseases; EVR: everolimus; HCV: hepatitis C virus; ILTS: 2011 Joint International Congress of the International Liver Transplantation Society; NS: nonsignificant; SRL: sirolimus; SVR: sustained virologic response; TAC: tacrolimus.